bluuebunny/crossref_metadata_2025_split huggingface dataset:
NT-proBNP (N-terminal prohorne of brain natriuretic peptide) as an early marker for detection of response to endothelin receptor antagonist in pulmonary arterial hypertension patients
Authors: Chang S.A , Lim K.H , Park J.B , Kim D.K , Kim H.K 
Published: November 2020

Abstract

Background
Endothelin receptor antagonist (ERA) is well-established for targeted therapy of pulmonary arterial hypertension (PAH). According to the guidelines, comprehensive evaluation of responses to PAH-targeted therapy is recommended 3 to 6 months after treatment onset. Early detection of response to ERA after starting new treatment may be of clinical value to establish next therapeutic plan.

Purpose
We sought to investigate whether NT-proBNP plays a reliable role for early maker of responses to ERA in PAH patients.

Methods
Sixty four patients (age &gt;19 years old) with a confirmatory diagnosis of PAH were enrolled who were treated with ERA (bosentan or macitentan) in two tertially PAH experts centers. NT-proBNP measurements were performed at baseline, 1 month and 6 months after ERA treatment. Clinical characteristics including WHO functional class, laboratory test, and echocardiographic results were systematically collected.

Result
Sixty four patients were finally analyzed who completed the 6 months of follow-up. Etiology of PAH was as follows: idiopathic PAH (n=25), connective tissue disease associated PAH (n=16) and congenital heart disease assocciated PAH (n=24). Mean age was 50±15 years-old and female were predominant (75%). NTproBNP level was changed from 703pg/ml [207–2748] at baseline, 301 pg/ml [126–1314] at 1 month and 297pg/ml [106–901] at 6 months after ERA treatment. Although, NT proBNP level in overall population was significantly decreased after ERA treatment, NT proBNP level before treatment showed poor correlation with those at 6 months (R2=0.32). However, change of NT proBNP at 1 month from baseline showed strongly correlated with change of NT proBNP at 6 months from baseline with linear regression model analysis (R2 =0.90, p&lt;0.001).

Conclusions
Assessment of early change in nt-proBNP with only a month of treatment is associated with midterm response to ERA treatment in PAH. It can help to early decision making for early intensive therapy and rapid escalation of PAH medication in non-responsive PAH patients for initial therapy.
The relationship of BNP

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Handok
The assessment of lung function and residual hypoxemia after balloon pulmonary angioplasty for patients with chronic thromboembolic hypertension
Authors: Matsuoka Y , Taniguchi Y , Keisuke M , Onishi H , Tsuboi Y , Otake H , Emoto N , Hirata K 
Published: November 2020

Abstract

Background
It has been reported that balloon pulmonary angioplasty (BPA) could dramatically improve hemodynamics in patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, some patients have shown poor response in oxygenation and lung function even after BPA. The aim of our study was to evaluate the efficacy of BPA using clinical indicators and to investigate lung function and residual hypoxemia.

Method
Consecutive 103 patients who underwent BPA from September 2011 to August 2018 were enrolled. We evaluated hemodynamics with right heart catheterization, respiratory function test, arterial blood gas examination, and exercise capacity with 6 minute-walk-distance (6MWD).

Result
At the median 12-month follow-up after the final BPA session, following examination findings were significantly improved. Mean pulmonary artery pressure (39.0±8.2mmHg, 23.2±8.4mmHg, p&lt;0.001), Pulmonary vascular resistance (782±378 dynes / sec / cm-5, 331±187 dynes / sec / cm-5, p&lt;0.001), 6 MWD (310±94 m, 363±119 m, p&lt;0.001), PaO2 (63.1±15.8 mmHg, 68.5±13.6 mmHg, p=0.044),%VC (88.5±17.1, 91±16.3, p=0.036). However, the following examination findings did not improve after BPA. Oxygen desaturation during 6MWD test (−11.9±6.3, 12±7.9, p=0.65), %DLCO (64.2 17.1, 61.3 16.8, p=0.147).

Conclusion
BPA could dramatically improve hemodynamics and exercise tolerance. However, arterial oxygenation was not normalized after BPA. Moreover, oxygen desaturation in exercise, and %DLCO were almost unchanged. These observations might suggest the remaining arteriopathy in capillary level of pulmonary artery, but further research is needed.

Funding Acknowledgement
Type of funding source: None
Differential effect of anticoagulant treatment on vascular morphology in patients with acute pulmonary embolism
Authors: Braams N.J , Boon G.J.A.M , Den Exter P.L , Kroft L.J.M , Beenen L.F.M , Huisman M.V , Vonk Noordegraaf A , Bogaard H.J , De Man F.S , Klok F.A , Meijboom L.J 
Published: November 2020

Abstract

Introduction
Chronic thromboembolic pulmonary hypertension (CTEPH) is described as one of the most severe consequence of acute pulmonary embolism (APE). When signs of chronic PE are present on the CT pulmonary angiogram (CTPA) used to diagnose APE, the question arises whether there is underlying CTEPH. The relevance of chronic lesions, as well as the effect of anticoagulant treatment on their development is currently unknown.

Purpose
To investigate the effect of anticoagulant treatment on CTPA derived vascular morphological abnormalities in patients with APE.

Methods
We performed a case-cohort study. As cases, we selected CTEPH patients who had a prior history of a first APE episode. As cohort, we selected patients who had a follow-up CTPA performed 6 months after first episode APE in the context of a clinical trial (den Exter 2015). A baseline (i.e. at moment of APE diagnosis) CTPA and a follow-up CTPA was available for all patients. Experienced chest radiologists morphologically assessed 20 segmental pulmonary arteries per patient as “normal” or “affected” (as defined by a total occlusion by thrombus, central thrombus, mural thrombus, web or tapered pulmonary artery). Pulmonary segmental vessels of the entire cohort were merged for the analysis. All patients were treated adequately with anticoagulant treatment (vitamin K antagonists, direct oral anticoagulation or low molecular weight heparin) in the period between baseline and follow-up CTPA according to current guidelines.

Results
A total of 30 cases and 116 controls were included. Mean time between baseline and follow-up CTPA was 193 (62) days. At baseline CTPA, 1647 (56%) of the 2920 pulmonary segmental vessels were scored as affected. Almost all central thrombi resolved after oral anticoagulant treatment (1103/1191=93%). Webs (n=85) and tapered pulmonary arteries (n=57) did not change in morphology at follow-up (Figure 1). Most vessels containing a total occlusion by a thrombus at baseline resolved completely (156/280=56%), changed to a tapered pulmonary artery (26%) or became a web (7%). Mural thrombi either remained unchanged (16/34=47%), resolved completely (29%) or became a web (24%).

Conclusion
After anticoagulant treatment for APE almost all central thrombi completely resolved, whereas mural thrombi or total occlusions by thrombi either resolved or transformed to a web or tapered pulmonary artery. Interestingly, none of the webs and tapered pulmonary arteries resolved after anticoagulant treatment. Therefore, webs and tapered pulmonary arteries at the moment of APE diagnosis indicate a chronic PE state.
Figure 1. Web at baseline and follow-up

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Research grant from Actelion Pharmaceuticals
Sleep-related breathing disorders in patients with pulmonary hypertension
Authors: Dyachenko M , Simakova M , Korostovtseva L , Bochkarev M , Sviryaev Y , Moiseeva O 
Published: November 2020

Abstract

Introduction
There are some evidences of sleep-related breathing disorders (SRBD) association with pulmonary hypertension (PH). Only limited information regarding the SRBD prevalence in pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients, is available.

Purpose
To estimate the features of SRBD and the asymmetric dimethylarginine (ADMA) level in PAH and CTEPH patients and their relationship with the severity of PH.

Methods
There were included 31 patients (45% male; 55% female) with a verified diagnosis of precapillary PH: 22.6% – with PAH; 9,7% with PAH associated with adult congenital heart disease; 64.5% – with CTEPH; 3.2% with PAH associated with connective tissue disease. Patients underwent a general clinical examination, questionnaires, a comprehensive assessment of respiratory function, a complete polysomnographic study, ECG and ECHO studies, assessment of clinical and biochemical blood tests, including an assessment of ADMA and NT-proBNP levels.

Results
SRBD of a predominantly obstructive nature were found in 74.2% of the examined: 38.7% were mild, 22.6% were moderate, 12.9% were severe. In 35% of patients, episodes of periodic breathing during sleep were recorded. There was no association SRBD with PH functional class and hemodynamic parameters. Moderate correlation was observed between the apnea-hypopnea index and remodeling indices of the heart chambers according to ECHO: for the end-diastolic size of the left ventricle (ρ=0.54; p=0.005); for an indicator of the ratio of the size of the ventricles (RV/LV) (ρ=−0.41, p=0.05). The presence of SRBD wasn't associated with the level of peripheral blood saturation according to pulse oximetry in sleep and during wakefulness. Negative moderate correlation was observed between NT-proBNP level and the average peripheral blood saturation at night in the entire examined group (ρ=−0.40; p=0.035). All patients showed an increase in ADMA, with no association between ADMA and SRBD severity.

Conclusions
The incidence of SRBD is extremely high in PAH and CTEPH patients. However, there no association between presence and severity of PH, including with right heart remodeling. But the severity of nocturnal hypoxemia is associated with an increase in NT-proBNP level, a proven marker of poor prognosis in PAH and CTEPH groups of patients. SRBD severity indices (apnea-hypopnea index and desaturation index) are associated with ECHO parameters characterizing remodeling of left heart chambers. Increasing ADMA level as a marker of endothelial dysfunction was related with PH severity, but not with SRBD.

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): Almazov National Medical Research Centre
Relationship between effects of riociguat and levels of methemoglobin in patients with chronic thromboembolic pulmonary hypertension
Authors: Sugimoto K , Nakazato K , Oikawa M , Kobayashi A , Yamaki T , Kunii H , Yoshihisa A , Ishida T , Takeishi Y 
Published: November 2020

Abstract

Background
Soluble guanyl cyclase (sGC) is a receptor for nitric oxide (NO) and plays an important role in vascular tonus. sGC stimulant is a therapeutic agent for pulmonary hypertension and an advantage of sGC stimulant over phosphodiesterase (PDE)-5 inhibitors is that sGC stimulant exerts its effect even when NO production is reduced. NO derived from vascular endothelial cells is immediately absorbed by hemoglobin (Hb), which leads to the production of methemoglobin (Met-Hb) when oxidized. Previous report has shown that the therapeutic effect of PDE-5 inhibitors was associated with levels of Met-Hb.

Purpose
In this study, we examined the relationship between the effect of riociguat and levels of Met-Hb in patients with chronic thromboembolic pulmonary hypertension (CTEPH).

Methods
The study population comprised 18 patients with CTEPH. Mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) were assessed before and after administration of riociguat, and changes in mPAP and PVR were defined as ΔmPAP and ΔPVR, respectively. Since the level of Met-Hb was obtained as the percentage of Hb (FMet-Hb), the amount of Met-Hb was calculated by following formula:
Met-Hb (mg/dL) = Hb (g/dL) × FMet-Hb (%) × 10.

Results
The amount of Met-Hb value before administration of riociguat was significantly correlated with the degree of improvement in mPAP and PVR after administration of riocigat (R=−0.502, P&lt;0.05 mPAP; R=−0.481, P&lt;0.05 PVR, respectively) as shown in figures.

Conclusion
Our findings suggest that the level of Met-Hb before treatment may predict the therapeutic effect of sGC stimulants in patients with CTEPH.

Funding Acknowledgement
Type of funding source: None
Comparison of pulmonary vascular resistance and pulmonary artery compliance during exercise between IPAH and CTEPH with normal pulmonary artery pressure
Authors: Nakata C , Takeuchi K , Kikuchi H , Goda A , Inami T , Satoh T , Soejima K 
Published: November 2020

Abstract

Background
Pulmonary vascular resistance (PVR) and pulmonary artery compliance (PAC) are inversely related. However, the little is known about dynamics during exercise by disease difference. The aim of this study was to reveal the relationships of PVR and PAC during exercise between idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients.

Methods
Sixty-two IPAH patients (45±9 y.o) and 359 CTEPH patients (63±13 y.o) with normal mean PAP and PAWP at rest underwent symptom-limited exercise test using supine cycle ergometer with right heart catheter.

Results
There were no differences between baseline mean PAP and PAWP in 2 groups, however, cardiac output, SaO2 and SvO2 were lower in CTEPH group. Lower PAC (2.9±1.1 vs. 3.7±1.7 ml/mmHg, p&lt;0.001) and higher PVR (2.3±1.0 vs. 1.9±1.0 wood.unit, p=0.016) were observed in CTEPH group. These trends were also seen at peak exercise. PVR-PAC relationship in CTEPH group was leftward shift compared with IPAH group (Figure 1).

Conclusion
Resting and exercise PVR and PAC in CTEPH patients were worse than those in IPAH patients who had normal PAP and PAWP at rest.
Figure 1

Funding Acknowledgement
Type of funding source: None
Change of myocardial fluorodeoxyglucose uptake distribution after specific therapy of pulmonary arterial hypertension patients
Authors: Kazimierczyk R , Szumowski P , Malek L.M , Blaszczak P , Jurgilewicz D , Hladunski M , Sobkowicz B , Mysliwiec J , Grzywna R , Musial W.J , Kaminski K.A 
Published: November 2020

Abstract

Background
Right ventricular (RV) function is a major determinant of survival in patients with pulmonary arterial hypertension (PAH). In our previous study, we confirmed that increased RV fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET) (presented as higher ratio of FDG uptake of RV to LV) was associated with progressive RV dysfunction and preceded hemodynamic and clinical deterioration in PAH patients. Now, we obtained second PET/MRI assessments of the study group after 2-years of PAH-targeted treatment.

Aim
The aim of the study was to obtain change of cardiac FDG uptake in PAH patients after follow-up period and to indicate factors mainly affecting this change.

Methods
Twenty-eight PAH patients (51.32±15.91 years) had simultaneous PET/MRI scans performed during baseline visit. FDG was used and its uptake was quantified as mean standardized uptake value (SUV) for both left (LV) and RV. Second PET/MRI assessments were done after 2 years in the group of twenty patients (four deaths, four patients did not agree to perform additional scans).

Results
After follow-up period, we observed significant change of MRI-derived RV ejection fraction (45±10% to 51.2±12.7%, p=0.03), and improvement in hemodynamic parameters obtained from right heart catheterization (RHC) e.g. mean pulmonary artery pressure, mPAP (48.5±17.2 to 41.8±17.1 mmHg, p=0.01) and pulmonary vascular resistance, PVR (8.7±5.3 to 7.0±4.2 WU, p=0.04). Follow-up SUVRV/SUVLV ratio significantly correlated with follow-up RV hemodynamic parameters confirming relationship between RV function and cardiac metabolic alterations (Table 1). Interestingly, patients who had improvement in SUVRV/SUVLV (lower follow-up value than baseline, n=11) had significantly higher mPAP at baseline visit (58.9±18.7 vs 40.3±11.8 mmHg, p=0.02), suggesting that RV FDG accumulation in advanced PAH may decrease after the PAH-specific treatment in accordance with the degree of reduction in the pulmonary vascular resistance.

Conclusion
Impaired RV function is associated with increased glucose uptake of RV myocytes estimated by FDG PET in PAH patients. Targeted treatment may improve RV function and thus affect previously altered cardiac glucose uptake.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): Polish National Science Centre
Aortic stiffness and hemodynamics in Loeys-Dietz syndrome by 4Dflow CMR: a comparison with healthy volunteers and patients with Marfan syndrome
Authors: Ruiz Munoz A , Guala A , Rodriguez-Palomares J.F , Dux-Santoy L , Servato L , Lopez-Sainz A , La Mura L , Gonzalez-Alujas T , Galian-Gay L , Gutierrez L , Johnson K , Wieben O , Ferreira I , Evangelista A , Teixido-Tura G 
Published: November 2020

Abstract

Background
Connective tissue disorders, such as Loeys-Dietz (LDS) and Marfan (MFS) syndromes, are rare genetic diseases associated with progressive aortic dilation. Aortic dissections have been observed at lower aortic root diameters in LDS than in MFS, and research on aortic flow dynamics and biomechanics in LDS is lacking.

Purpose
To evaluate rotational aortic flow and aortic stiffness in LDS compared to healthy volunteers (HV) and MFS patients, using 4Dflow CMR.

Methods
Twenty-one LDS and 44 MFS patients, without previous aortic dissection or surgery, and 44 HV underwent a non-contrast-enhanced 4D flow CMR. In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR) and local aortic diameters were obtained at 20 equidistant planes from the ascending (AAo) to the proximal descending aorta (DAo). Aortic stiffness was quantified at the AAo and DAo using pulse wave velocity (PWV).

Results
LDS patients had lower IRF at the distal AAo and proximal DAo compared to HV (p=0.053 and 0.004, respectively), once adjusted for age, stroke volume and local aortic diameter; but no differences were found with respect to MFS (Figure). Although SFRR at the proximal DAo was increased in LDS patients compared to both HV (p=0.037) and MFS populations (p=0.015), once adjusted for age and aortic diameter, the difference in magnitude was small (Figure). On the other hand, AAo and DAo PWV revealed stiffer aortas in LDS patients compared to HV but no differences versus MFS patients (Table).

Conclusions
LDS patients showed decreased in-plane rotational flow and abnormally-high regional aortic stiffness compared to healthy controls, and similar hemodynamics and aortic stiffness with respect to MFS patients

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): Instituto de Salud Carlos III, La Maratό TV3
Sex-related differences in clinical features and in-hospital outcomes of acute aortic dissection type b
Authors: Takahashi T , Yoshino H , Akutsu K , Shimokawa T , Ogino H , Kunihara T , Usui M , Watanabe K , Kawata M , Masuhara H , Yamasaki M , Hagiya K , Yamamoto T , Nagao K , Takayama M 
Published: November 2020

Abstract

Background
Acute aortic dissection (AAD) is a life-threatening medical condition with high morbidity and mortality. The association between female sex and poorer outcomes following surgery for AAD type A has been reported; however, the sex-related differences in clinical features and in-hospital outcomes of AAD type B remain to be elucidated.

Methods
We studied a total of 1877 patients with AAD type B who were enrolled in the Tokyo Acute Aortic Super-network from January 2013 to December 2016. Clinical features and in-hospital outcomes were compared between sexes. Independent predictors of in-hospital mortality were assessed using a multivariable analysis.

Results
The mean age of the patients was 69±13 years and 549 (29%) were females. Female patients were older than males (74±13 years vs 67±13 years; p&lt;0.001). Females had lower systolic blood pressure on admission (158±37 mmHg vs 164±38 mmHg; p=0.007) and were more likely to have altered consciousness level at presentation (8.7% vs 3.9%; p&lt;0.001), intramural hematoma (IMH)-type AAD (62.7% vs 53.6%; p&lt;0.001), and DeBakey type IIIa (28.4% vs 21.8%; p=0.002) compared with males. Females were treated with medical therapy alone more frequently (90.3% vs 85.9%; p=0.009) and had a higher in-hospital mortality rate (5.3% vs 2.6%; p=0.036). A multivariable analysis revealed that age [per year, odds ratio (OR) 1.06; 95% CI 1.04–1.09; p&lt;0.001], altered consciousness level (OR 3.28; 95% CI 1.54–6.98; p=0.002), shock/hypotension (OR 14.0; 95% CI 5.92–33.1; p&lt;0.001), classic-type AAD (OR 2.54; 95% CI 1.36–4.73; p=0.003), and medical therapy alone (OR 0.28; 95% CI 0.15–0.54; p&lt;0.001) were independent predictors of in-hospital mortality, whereas female sex was not predictive of in-hospital mortality (OR 1.64; 95% CI 0.91–2.96; p=0.10).

Conclusion
In AAD type B, females were older and had altered consciousness level, IMH-type, and a less widespread dissection more frequently than males. The overall in-hospital mortality was higher in females; however, female sex was not associated with in-hospital mortality after multivariable adjustment.

Funding Acknowledgement
Type of funding source: None
Association of osteoprotegerin with ascending aortic dissection
Authors: Goliopoulou A , Antonopoulos A , Oikonomou E , Miliou A , Theofilis P , Skotsimara G , Mystakidi V.C , Tousoulis D 
Published: November 2020

Abstract

Background
Thoracic aortic dissections are among the cardiovascular diseases with the highest mortality rates. Their often belated diagnosis and, hence, poor prognosis call for further research of their pathophysiology and possible biomarkers that will aid early diagnosis and increase survival rates. Osteoprotegerin is a known biomarker in cardiovascular disease, but it is yet to be determined whether it participates in aortic disease and thoracic aortic dissection in particular.

Purpose
This clinical study aimed at researching the role of osteoprotegerin in thoracic aortic aneurysm and dissection.

Methods
We compared three groups of patients; 20 patients with ascending aortic aneurysm (AAA), 10 patients with acute ascending aortic dissection (AAD) and 16 patients with normal aortic diameter undergoing cardiac surgery for other indication (control group). Serum samples were obtained from patients before surgery and osteoprotegerin levels were measured using the ELISA method.

Results
One-way analysis of variance revealed a significant association between the examined groups of patients and levels of osteoprotegerin (AAD: 62.72±44.53 pmol/L, AAA: 33.43±8.08 pmol/L, Control: 48.61±29.47 pmol/L, p=0.03). Importantly, after post-hoc analysis osteoprotegerin levels were found to be increased in patients with AAD compared to patients with uncomplicated AAA (62.72±44.53 pmol/L vs 33.43±8.08 pmol/L, p=0.03) (Figure 1), whereas there was no statistically significant difference between patients with AAA and the control group (33.43±8.08 pmol/L vs 48.61±29.47 pmol/L, p=0.34).

Conclusions
These findings suggest that osteoprotegerin may participate in the pathophysiology of aortic dissection but not in mechanisms of aortic dilatation. Therefore, detection of elevated osteoprotegerin levels in patients with diagnosed ascending aortic aneurysms might suggest an increased probability of dissection and, therefore, aid the decision-making process.
Figure 1

Funding Acknowledgement
Type of funding source: None