bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-related differences in the effect of balloon pulmonary angioplasty on cardiac output in chronic thromboembolic pulmonary hypertension
Authors: Shimokawahara H , Kanezawa M , Matsubara H 
Published: October 2022

Abstract

Background
Balloon pulmonary angioplasty (BPA) has been accepted as an alternative for inoperable patients with chronic thromboembolic pulmonary hypertension (CTEPH). Although BPA improves most of the hemodynamic parameters, the improvement of cardiac output (CO) after BPA cannot be obtained in all the patients.

Purpose
This study was aimed to clarify whether BPA could improve CO or not. We also investigated the determinants for the improvement of CO after BPA.

Methods
We enrolled in consecutive 317 CTEPH patients treated with BPA in our hospital. All the patients were divided into three groups by generations (Younger group; age &lt;60 years old, n=103, Middle-aged group; 60 ≤ age &lt; 70 years old, n=100, Elderly group; 70 ≤ age, n=114). We retrospectively investigated the change of CO after BPA, including its determinants as heart rate (HR) and stroke volume (SV) among the three groups.

Results
Baseline mean pulmonary arterial pressure and six minutes-walk distance in the elderly group were lower than those in the younger group. Baseline CO was almost similar among the three groups. All the hemodynamic parameters, excluding CO, were improved after BPA in overall patients' analyses. The significant improvement in CO after BPA was identified only in the younger patients. Whereas HR decreased after BPA in all age groups, the improvement of CO and SV depended on each patient's generation, as shown in Figure 1.

Conclusions
It would be challenging to improve CO after BPA in all the populations, especially in elderly CTEPH patients. Adjuvant medical treatment in addition to BPA would be required in elderly patients.

Funding Acknowledgement
Type of funding sources: None.
Prevalence of pulmonary embolism among patients presenting to emergency department for hemoptysis
Authors: Vanni S , Gori L , Coppa A , Nazerian P , Giannasi G , Ruggiano G , De Curtis E , Baldini A , Pepe G , Magazzini S 
Published: October 2022

Abstract

Background
Although hemoptysis is a well known symptom of presentation of pulmonary embolism (PE), and it is included in different diagnostic scores for PE, the prevalence of PE in patients with hemoptysis and the yield of evidence based PE diagnostic pathway in these patients has not been specifically investigated.

Objectives
To determine the prevalence of PE and the yield (n° of positive tests/n° of tests), the efficiency (the proportion of patients in whom PE could be considered to be excluded) and the failure rate (the false negative rate) of the classic diagnostic algorithm for PE in patients with hemoptysis.

Methods
Unselected patients presenting with hemoptysis to 7 italian EDs were prospectively enrolled in a diagnostic multicenter study. Pre-test clinical probability for PE was assessed using the 2-level Wells score and the results of D-dimer testing using age-adjusted cutoffs. Presence of PE was evaluated by CT pulmonary angiogram (CTPA), when ordered as part of the clinical assessment by the treating ED physician, or by one month follow-up data.

Results
Out of 327 adult patients presenting to ED with hemoptysis, 15 (4.6%) were excluded because of diagnostic protocol violation and absence of one month follow-up. Among 312 included patients, PE was detected at presentation in 15 patients (4.8%; 95% confidence interval [CI]: 2.72–7.81%). During follow-up, 5 patients died (1.6%; 95% CI: 0.52%-3.7%) not due to PE. Among 165 patients with a “likely” score or a high D-dimer, 13 (7.9%; 95% CI: 4.72–13.8%) had PE. The efficiency was 32.8% and the failure rate was 1.7% in patients tested by D-dimer.

Conclusions
PE seems an uncommon cause of hemoptysis among patients presenting to the ED and the yield of classic diagnostic algorithm is low. PE-screening in patients with hemoptysis deserves further investigation aimed at improving the diagnostic yield.

Funding Acknowledgement
Type of funding sources: None.
Chronic thromboembolic pulmonary hypertension and left ventricular filling pressures
Authors: Gerges C , Pistritto A M , Gerges M , Friewald R , Hofbauer T , Hartig V , Dannenberg V , Skoro-Sajer N , Moser B , Taghavi S , Klepetko W , Lang I M 
Published: October 2022

Abstract

Background
Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by chronic obstruction of major pulmonary arteries with organized thrombi and is classified as pre-capillary pulmonary hypertension (PH) by the current hemodynamic definition of the guidelines. However, clinical risk factors for PH due to left heart disease including features of the metabolic syndrome, left-sided valvular heart disease and stable ischemic heart disease can be frequently observed in patients with CTEPH. The aim of this study was to investigate the prevalence, mechanisms and prognostic implications of elevated left ventricular filling pressures (LVFP) in patients with CTEPH.

Methods
394 consecutive CTEPH patients undergoing a first diagnostic right and left heart catheterization were included in this study. mPAWP and LVEDP were utilized for assessment of LVFP. Two cutoffs were applied to identify patients with elevated LVFP: (1) mPAWP and/or LVEDP &gt;15 mmHg as recommended by the current PH guidelines and (2) mPAWP and/or LVEDP &gt;11 mmHg, which is the upper limit of normal in healthy subjects. Clinical and echocardiographic features as well as long-term mortality data were assessed.

Results
LVFP was &gt;15 mmHg in 41 (10.4%) and &gt;11 mmHg in 155 patients (39.3%). Univariable logistic regression analysis identified age, body mass index, systemic hypertension, diabetes, atrial fibrillation, mitral regurgitation and left atrial volume as significant clinical predictors of elevated LVFP. Systemic hypertension, atrial fibrillation, mitral regurgitation and left atrial volume remained independent determinants of LVFP in adjusted analysis. LVFP &gt;11 mmHg was associated with worse long-term survival (p-logrank = 0.020).

Conclusions
Elevated LVFP is common in patients with CTEPH at the time of diagnosis. Elevated LVFP in CTEPH appears to be due to comorbid left heart disease. CTEPH patients with LVFP &gt;11 mmHg have worse outcomes.

Funding Acknowledgement
Type of funding sources: None.
Pulmonary hypertension – an explorative metabolomic analysis of the endothelium
Authors: Henriksen H , Johansson P J O , De Mas I D M , Carlsen J C 
Published: October 2022

Abstract

Background
Pulmonary hypertension (PH) is classified into five clinical diagnostic groups, including group 1 (idiopathic pulmonary arterial hypertension (IPAH) and connective tissue disease-associated PAH (CTD-aPAH)) and group 4 (chronic thromboembolic pulmonary hypertension (CTEPH)). PH is a progressive, life-threatening, incurable disease. The pathological mechanisms underlying PH remain elusive; recent evidence has revealed that abnormal metabolic activities in the endothelium may play a crucial role.

Purpose
Introducing a novel approach for studying PH endothelial function, building on genome-scale metabolic (GEM) reconstruction of the endothelial cell (EC) to investigate intracellular metabolism.

Methods
This prospective observational study includes 35 PH patients with either PAH or CTEPH. We have previously developed a platform to study the endothelium cell (EC) by reconstructing the most comprehensive endothelial genome-scale metabolic model (EC-GEM). Since the EC is in direct contact with the blood flow, we can adjust the EC-GEM by measuring extracellular metabolites from the blood and calculating the intracellular metabolic flux in the EC. We conducted individual EC-GEM models, i.e., in total 35 different models. Additionally, each model was widely analyzed; in total, 190 different intracellular activities were investigated. This enables us to develop a heatmap of the intracellular activities at individual patient levels. Patients with similar intracellular endothelial activities were combined.

Results
Four distinct intracellular phenotypes were identified; all were independent of the clinical classification of PH. We observed clinically relevant differences in the NT-pro BNP levels and the WHO functional classification between these phenotypes. Also, different important cellular activities were identified separating the four phenotypes. Two phenotypes were characterized by catabolic crisis and extreme citric acid cycle turnover for energy production. However, one of these also suffered from oxidative stress.

Conclusion
In PH patients metabolic systems analysis identified four metabolic phenotypes that correlated with NT-pro BNP levels and the WHO functional classification but were independent of the clinical diagnosis. This novel finding may enable us to identify metabolic therapeutic targets specific to the respective phenotypes and thus promote personalized medicine in patients with PH.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): This study was funded by Novo Nordisk Foundation research grant NNF20OC0064556 and the Heart Center Research Council, Copenhagen University Hospital, Rigshospitalet, provided to Jørn Carlsen
First genetic characteristics of Polish patients with idiopathic pulmonary arterial hypertension
Authors: Jonas K , Borys A , Wolkow P , Kopec G 
Published: October 2022

Abstract

Introduction
Pulmonary arterial hypertension (PAH) is a rare, severe disorder of multifactorial origin. Genetic alterations in BMP/SMAD pathways were previously associated with disease development, however the exact role of other genetic factors from BMP/SMAD signalling is still unclear.

Purpose
We aimed to search for known PAH-associated mutations and potential novel variants responsible for disease onset in Polish PAH patients.

Methods
We prospectively recruited 93 consecutive idiopathic PAH patients from a single pulmonary hypertension reference centre between years 2009 and 2020. Eligible patients had pre-capillary pulmonary hypertension with pulmonary vascular resistance &gt;3 Wood units in the absence of other causes of pre-capillary pulmonary hypertension. The presence of large gene rearrangements was analyzed by the Multiplex Ligation-dependent Probe Amplification (MLPA) reactions in the ENG, ACVRL1 and BMPR2 genes (SALSA MLPA Kit, MRC-Holland). We have further sequenced a panel of selected 48 genes from BMP/SMAD and related pathways using next-generation sequencing (SureSelect XT library preparation Kit, Agilent; NextSeq 500 sequencer, Illumina) and assessed causative potential of rare variants (minor allele frequency in non-finish Europeans below 1%) with Mutation Taster web-based tool.

Results
We identified at least one likely-causative variant of investigated genes in 51 (54.8%) subjects. Large genomic rearrangements were found by MLPA in 2 patients in ENG and ACVRL1 (ALK1) genes. We have found mutations in BMPR2 gene in 12 patients (12.5%) from our cohort with most variants present in one sample and 3 variants present in 2 samples. Mutations were located mostly in protein kinase domain (6 variants) and Activin type I and II receptor domain (2 variants). We have found 5 likely pathogenic variants in 6 patients in genes previously associated with PAH other than BMPR2 (SMAD9, KCNA5, KCNK3, EIF2AK4). In total, potentially disease causing mutations in literature-known genes, were present in 18 patients, which accounted for 18.75% of tested cohort. Medium impact variants were also present in KCNA5, TGFBR2, AQP7, BMP6, EIF2AK4, FBP1, NOTCH1, NOTCH3, SMAD7, TBX4, TGFB2, TOPBP1, GDF5, IL6, PPARA, RXRA, KCNK3, KLF4, BMPR1B, ILK, TGFBR1, SMAD9, PPARD and TGFB3 genes. Additionally, in one patient with clinical diagnosis of pulmonary venoocclusive disease we identified an unknown homozygous frameshift variant (p.Phe1523fs/c.4567_4570delTTTG) in exon 35 of EIF2AK4 gene.

Conclusions
We found potentially disease causing mutations in 18,75% Polish patients diagnosed with IPAH most of them were present in BMPR2 gene which is in line with data from other European cohorts. Additionally we found an unknown mutation in the EIF2AK4 gene.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Narodowe Centrum Nauki - National Science Centre
Determinants for residual symptoms in chronic thromboembolic pulmonary hypertension patients with mean pulmonary arterial pressure &lt;25 mmHg after balloon pulmonary angioplasty
Authors: Miyagi A , Shimokawahara H , Sugiyama Y , Suetomi T , Ogawa A , Matsubara H 
Published: October 2022

Abstract

Background
Balloon pulmonary angioplasty (BPA) improves hemodynamics and exercise capacity in inoperable patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, some symptoms, such as dyspnea on exertion, had remained in more than half of the patients even after BPA could decrease mean pulmonary artery pressure (PAP) &lt;25 mmHg in a Japanese multicenter registry. In addition, previous report indicated that impaired exercise capacity was observed in about half of the patients with CTEPH who achieved mean PAP &lt;25 mmHg at rest after BPA. Lowering mean PAP alone would not be sufficient as a treatment goal of BPA to eliminate residual symptoms in the patients.

Purpose
The purpose of this study was to elucidate the determinants of residual symptom in patients who had achieved mean PAP &lt;25 mmHg after BPA.

Methods
Among 310 CTEPH patients who received BPA in our center, 217 patients (70.0%) could achieve mean PAP &lt;25mmHg at six months after the final BPA were enrolled in this study. The patients were divided into two groups based on the necessity of additional BPA due to residual symptoms; additional BPA group and non-additional BPA group. Clinical parameters including resting hemodynamics at 6 months follow up were retrospectively investigated between the two groups.

Results
Additional BPA had been underwent in 67 patients (30.9%). No significant differences in mean PAP were identified between the additional and non-additional BPA groups (20.4±2.5 mmHg vs. 19.7±2.7 mmHg, p=0.106). In additional BPA group, cardiac index (CI), heart rate (HR) and percutaneous oxygen saturation (SpO2) was lower than non-additional BPA group, and pulmonary vascular resistance (PVR) was higher than non-additional BPA group (CI, 2.51±0.41 L/min/m2 vs. 2.72±0.56 L/min/m2, p=0.016, HR, 62.9±9.7 bpm vs. 67.8±10.8 bpm, p=0.003, SpO2, 94.3±3.7% vs. 95.9±3.5%, p&lt;0.001, PVR, 3.67±1.18 W.U. vs. 3.11±1.09 W.U. p=0.001). In a multivariate analysis, CI, SpO2 and PVR were associated with residual symptoms requiring additional treatment in patients with mean PAP &lt;25mmHg after BPA (95% confidence interval: CI; 0.221–0.900, SpO2; 0.825–0.976, PVR; 1.000–1.785).

Conclusion
Low CI and SpO2 and High PVR were determinants for residual symptoms in CTEPH patients who could achieve mean PAP &lt;25 mmHg after BPA. To eliminate the residual symptoms, treatment goals of BPA in inoperable CTEPH patients should be increasing CI and SpO2 and lowering PVR in addition to normalizing mean PAP.

Funding Acknowledgement
Type of funding sources: None.
Evaluation of acute chest pain – is it possible to associate cardiovascular risk scores (TIMI, HEART, GRACE) and the presence of obstructive plaque on coronary computed tomography angiography?
Authors: Souto M J S , Aguiar M G , Toledo L N , Gueiral H D , Guiguer I C , Morales P A S , Pinto I M F , Gun C , Paladino F A T 
Published: October 2022

Abstract

Introduction
Coronary artery disease (CAD) answers for almost 43.2% of cardiovascular deaths worldwide. In the United States, more than 8 million patients present to the emergency department each year with acute chest pain. Although, as few as 10% will be diagnosed with acute coronary syndrome. Cardiovascular risk scores are frequently used as tools to evaluate the chance of coronary disease, despite the fact that they were initially validated as prognostic schemes to categorize a patient's risk of death and ischemic events. The association of these scores and the presence of obstructive atherosclerotic plaques is scarce.

Purpose
To associate the presence of obstructive atherosclerotic plaque on coronary computed tomography angiography (CCTA) and cardiovascular risk scores, in the evaluation of patients who present with acute chest pain to the emergency department in a tertiary referral center in cardiovascular disease.

Methods
This is an observational and retrospective study that evaluated patients presenting to the emergency department with acute chest pain and were referred to CCTA. Exclusion criteria were ischemic EKG signs, positive troponin or history of coronary revascularization. CCTA images were reviewed by trained observers who performed a per-segment analysis to assess coronary artery stenosis, with complex cases classified by consensus. Atherosclerotic plaque was categorized as obstructive if luminal cross-sectional area stenosis was &gt;50% in ≥1 major epicardial artery.

Results
Overall, 350 patients were recruited (52.6±11.9 years, 50% women) in whom 20.6% (72 patients) had significant atherosclerotic plaque. Male gender (OR: 1.87; 95% CI: 1.08–3.26), age &gt;52 years (OR: 2.85; 95% CI: 1.6–5.07), diabetes (OR: 2.17; 95% CI: 1.12–4.2) and typical angina (OR: 2.17; 95% CI: 1.12–4.2) were the only clinical characteristics independently associated with the presence of obstructive plaque. More then 90% of patients with significant coronary stenosis were classified as low risk by GRACE and TIMI scores. HEART score was &lt;4 in 23.6% of patients with obstructive plaque.

Conclusion
In patients who present to the emergency department in a tertiary referral hospital with acute chest pain, the initial evaluation based on clinical characteristics and cardiovascular risk scores was not sufficient to exclude safely the presence of coronary artery disease. Therefore, in such patients, CCTA could help to identify those with occult CAD and to target preventative treatments, thereby improving clinical outcomes.

Funding Acknowledgement
Type of funding sources: None.
The prognostic value of vasoresponse to nitric oxide in patients with chronic thromboembolic pulmonary hypertension
Authors: Uphus J , Hu J R , Huang S , Panzenboeck A , Sadushi-Kolici R , Shafran I , Skoro-Sajer N , Gerges C , Brittain E , Lang I M 
Published: October 2022

Abstract

Background
Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by pulmonary artery obstructions due to organized chronic thrombotic material in major pulmonary arteries. In addition, about half of the patients suffer from a small vessel pulmonary arteriopathy that is a strong predictor of outcomes. Currently available treatment of CTEPH includes interventional strategies such as pulmonary endarterectomy (PEA) and balloon pulmonary angioplasty (BPA), and non-interventional strategies with PH-specific medications. A simple way of assessing small vessel disease is the degree of vasodilation (“vasoresponse”) in response to inhaled nitric oxide (iNO). In idiopathic pulmonary arterial hypertension vasoresponse serves as the best marker for good prognosis and treatment selection. In CTEPH, the prognostic value of vasoresponse remains unclear.

Purpose
We investigated the prognostic value of three definitions of vasoresponse to nitric oxide in patients with CTEPH.

Methods
We studied 325 CTEPH patients who underwent baseline diagnostic right heart catheterization (RHC) with 40ppm iNO testing at a general hospital (AKH) between 1995 and 2019. Cox regression models, adjusting for covariates including age, sex, comorbidities, and markers for disease severity at baseline, such as proBNP, GFR, NYHA functional class, were used to determine the risk of death or lung transplantation with respect to vasoresponse. We analysed three currently used definitions of vasoresponse to nitric oxide – the classical definition (CD) as a 10mmHg reduction in mPAP to a level below 40mmHg; an absolute definition (AD) as a 10mmHg reduction in mPAP regardless of resulting mPAP; and the percent definition (PD) as a 10% reduction in mPAP regardless of resulting mPAP.

Results
Patients had a median age of 62 (interquartile range [IQR]: 50, 71) at time of baseline right heart catheterization and 50% were female. During a median observation time of 5 years (IQR: 2.2, 9.0), the combined endpoint of death or lung transplantation occurred in 88 cases (27%). In the cox regression model PD vasoresponders, showed improved survival when undergoing PEA (p=0.0019). In PD vasoresponsive patients who were not given PEA surgery (n=66), PH medication therapy was associated with improved survival (p=0.0053), whereas BPA had no association with survival (p=0.58). In PD non-vasoresponsive patients who were not given PEA surgery (n=107) BPA improved survival (p&lt;0.0001), whereas PH medication therapy did not improve survival (p=0.08).

Conclusion
The PD vasoresponse to iNO carries valuable prognostic information about freedom from death or lung transplantation in patients with CTEPH. In patients who are not eligible for PEA, PD vasoresponse can improve optimal therapy selection.

Funding Acknowledgement
Type of funding sources: None.
Body size in adolescence and future risk of Aortic disease: a nationwide cohort study of Swedish men
Authors: Nielsen S N , Djekic D D , Robertson J R , Adiels M A , Aberg N D , Jeppsson A J , Aberg M A , Lindgren M 
Published: October 2022

Abstract

Background
To improve cardiovascular disease prevention, knowledge of early key risk factors for aortic disease (AD), especially those that are modifiable such as overweight and obesity, is essential. Therefore, we aimed to determine whether measures of body size, including body mass index (BMI), body surface area (BSA) and body height in adolescent men is associated to AD later in life.

Methods
Register-based cohort study of conscripts (n=1,575,909; mean age at baseline, 18.3 years) who enlisted during 1968–2005 in Sweden. Follow-up was done through linkage to the nationwide Swedish inpatient- and cause of death registries. Risk of AD (hospitalization for Aortic aneurysm or aortic dissection) during follow-up (5–48 years) was calculated with cox proportional hazard models.

Results
During follow-up there were 8185 cases of AD. Incidence rates (per 100000 person years) increased with increasing body size measures; BSA 14.19 (95% CI, 13.6–14.8) for Q1 vs 19.36 (18.6–20.2) for Q4; BMI 15.89 (15.2–16.6) for Q1 vs. 16.89 (16.2–17.6) for Q4; and body height 13.45 (95% CI, 12.9–14.1) for Q1 vs 19.93 (95% CI, 19.1–20.8) for Q4. Compared to the lowest, the highest quartile of BSA and body height was associated with increased risk of AD (adjusted HR (aHR) 1.95 (95% confidence interval 1.83–2.08) and 1.72 (1.62–1.83) respectively). For BMI, the corresponding aHR was 1.40 (1.31–1.49, Figure 1).

Conclusion
Large body size in early adulthood is associated with risk for aortic disease later in life. The pathophysiological mechanisms remain uncertain and warrants further investigation.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Swedish state under the agreement concerning research and education of doctors [grant number ALFGBG-427301]; the Swedish Society for Physicians, the Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, Sweden, and the Swedish Heart and Lung Foundation [grant number 2015-0438]; the Swedish Research Council [grant numbers 2013-5187 (SIMSAM), 2013-4236]; and the Swedish Council for Health, Working Life and Welfare (FORTE) [grant numbers 2013-0325]