bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reversibility and outcome of fenestrated surgical closure in adult patients with congenital left-to-right shunts and pulmonary hypertension: a result of cohard-ph registry
Authors: Anggrahini D W , Haidar S , Hartopo A B , Dinarti L K 
Published: November 2023

Abstract

Background
Uncorrected congenital heart disease in the adults often come with a complication of pulmonary hypertension (PH) , resulting in high mortality and low quality of life due to right heart failure and arrythmias. Shunt closure in those patients has been shown to reduce such complications. However, in patients who develop PH, total shunt closure posseses risk that increase mortality. ESC guidelines recommend avoidance of ASD closure and careful evaluation of VSD and PDA closure in those with PVRI&gt;5 WU. Nevertheless, some Asian countries reported good outcome in LtoR shunt closure in patients with PVRI&gt;5.
Congenital Heart Disease in Adults and Pulmonary Hypertension (COHARD-PH) Registry is a single tertiary center registry in Indonesia. The data showed that among congenital LtoR shunts, PAH occurred in 66.9% patients and Eisenmenger Syndrome in 18.7%. In this study we aim to evaluate the outcome and the PH reversibility of adult patients underwent fenestrated closure in this registry.

Methods
Patients with intracardiac shunts who underwent surgical closure with atrial septal fenestration on January 2019-July 2022 were recruited and the follow-up data was obtained within 6 months after surgery.

Results
Thirty-eight patients underwent surgical fenestrated closure were identified. Age was ranging between 19-70 (mean 39) years-old and 81.6% were female. Thirty patients (30%) were ASD, 7 (18.4%) were VSD, and 1 patient (2.6%) was incomplete AVSD. All patients underwent 4-5 mm atrial septal fenestration despite the repair of their anatomical lesion. Hemodynamic measurement before surgery showed that the average Qp/Qs was 3.2; mPAP 51±17 mmHg and the mean pulmonary vascular resistance index (PVRI) was 7.2±4.4 WU before surgery. We performed acute vasoreactivity test (AVT) to 21 patients and showed positive result, while the rest of the patients did not have AVT due to PVRI of 4 WU or less.
Short and mid-term follow up reveal a mean SICU length of stay was 2.5 days and mean total hospital stay was 9 days. Three patients died during their hospital stay after discharged from the SICU due to post operative sepsis. On 6 month follow up, the remaining 35 subjects have no remaining symptoms. The reversibility of PH was assesed by echocardiography and showed that mean TVG was reduced from 78 to 36 (by 54%). None of these patients showed signs of heart failure or pulmonary hypertension on follow up.

Conclusion
Atrial septal fenestration in patients with adult congenital left to right shunt undergoing surgical closure might be considered in selected patients with pulmonary hypertension including those with positive acute vasoreactivity test. Further study with larger subjects is warranted to evaluate the current guidelines.
Total pulmonary resistance as assessed by non-invasive pressure-flow plots is related to exercise capacity in Fontan patients
Authors: Cieplucha A , Troost E , Budts W , De Meester P , Bekhuis Y , Rosseel T , Van Puyvelde J , Van De Bruaene A 
Published: November 2023

Abstract

Background
In Fontan patients, the slope of invasively measured pulmonary artery pressures plotted against cardiac output (CO) during exercise has prognostic significance. We propose a methodology using exercise echocardiography combined with cardiopulmonary exercise testing and simultaneous peripheral venous pressure measurements (CPET-echo-PVP) to calculate PVP/CO slopes as a non-invasive alternative.

Purposes
This study aimed at assessing (1) PVP/CO slopes and (2) their relationship with peak oxygen consumption in Fontan patients.

Material and Methods
Consecutive adult Fontan patients seen in the outpatient clinic at UZ Leuven, Belgium were included in the study. All patients underwent CPET-echo-PVP (peripheral intravenous line connected to the pressure transducer zeroed at the mid-axillary level). Bloodwork was performed, including N-terminal prohormone of brain natriuretic peptide (NTproBNP). The PVP/CO slope was calculated as a linear approximation using linear regression analysis from pressure-flow plots for each patient. Univariable regression analysis was performed to identify potential determinants of PVP/CO slope.

Results
In total 20 patients (mean age 30.5±10.4 (range 20-60), 11[55%] females, dominant left ventricle in 15 [75%]) were included. NT-proBNP was 297±235 pg/mL. Patients performed staged exercise test achieving workload of 102±30 Watts with a peak oxygen consumption (peakVO2) of 19.2±3.8 mL/kg/min. During exercise cardiac output (CO), heart rate (HR) and PVP all increased (mean difference: 4.1±2.2L/min, 57±26bpm, 10.4±5.9mmHg, respectively). Stroke volume index (SVind) increased from baseline to peak exercise in 9 (45%) (mean difference -2.6±12.0mL/m2). The average PVP/CO slope was 2.21±1.53mmHg/L*min, with the value exceeding 3mmHg/L*min in 5 (25%) patients. PeakVO2, peak Workload during exercise, NTproBNP, New York Heart Association (NYHA) class, and rest-to-peak change in tissue-Doppler e’ (delta e’) of the lateral wall of dominant ventricle were significantly related to the PVP/CO slope (all p&lt;0.05).

Conclusions
CPET-echo with PVP is a reliable method to identify determinants of exercise limitation in Fontan patients. The PVP/CO slope, which reflects total pulmonary resistance, is indeed related to peak oxygen consumption, heart rate reserve and diastolic function. Since it reflects hydraulic load to the systemic venous system it may be an important target in Fontan patients.
Alternations of N6-methyladenosine RNA methylation landscape in pulmonary arterial hypertension
Authors: Song J , Feng Y , Li J , Tang M , Liu Q 
Published: November 2023

Abstract

Background
N6-methyladenosine (m6A) methylation is the most prevalent and abundant RNA modifications in eukaryotes. Deregulation of m6A changes by m6A-specific enzymes can affect the stability and function of transcripts. However, the relevance of m6A mRNA and m6A-specific enzymes in pulmonary arterial hypertension (PAH) have not been extensively explored.

Objectives
This study aimed to analyze m6A methylation transcriptomic profiling in the pulmonary arteries of PAH rats, and to find potential m6A regulators corelated with PAH epi-transcriptomic changes.

Methods
MeRIP-seq and RNA-seq were applied to identify differences in m6A methylation and gene expression in pulmonary artery tissues from control and monocrotaline PAH rats. The expression of a m6A regulator in pulmonary arteries was further analyzed by western blot, flow cytometry, immunohistochemical staining and immunofluorescence. The proliferation and apoptosis assays were further performed in primary rat pulmonary artery smooth muscle cells (PASMCs).

Results
Twenty-seven differentially expressed genes with hypermethylated or hypomethylated m6A modifications were identified. These differentially expressed genes were mainly linked to the extracellular matrix and structure, MAPK and PI3K-Akt signaling pathways. Furthermore, we firstly detected a m6A reader leucine rich pentatricopeptide repeat containing (LRPPRC) with downregulated expression in PAH rats. PASMCs with a siRNA knockdown of the LRPPRC promoted proliferation and apoptotic resistance.

Conclusion
This study showed that altered m6A transcriptome-wide landscape and relevant regulatory mechanisms of the PAH pulmonary artery tissues in rats, which might provide a new and potential target for therapeutic interventions in PAH.LRPPRC functional studies in PASMCs
S wave resolution in standard electrocardiography aVL lead in 48 hours from admission of severe acute pulmonary embolism is associated to favorable outcome in various subgroups of patients
Authors: Obradovic S , Dzudovic B , Matijasevic J , Salinger S 
Published: November 2023

Abstract

Background
An electrocardiography record does not serve for the diagnosis of pulmonary embolism. Still, it can indirectly, accurately, and without delay display acute right ventricle overload which represents the main feature of the severe disease. The aim of this study is to investigate the association of a single ECG sign change, the resolution of S wave in aVL lead with the outcome of severe PE patients.

Methods
Data from this investigation are gained from the Regional PE Registry (REPER) with prospectively variable definition and collection. Among 1814 patients with acute PE, 212 intermediate-high and high-risk PE patients had recorded S wave in aVL and if there was a resolution of this sign in the 48 hours from the admission to the hospital. Of the 145 (68.4%) were treated with thrombolytic therapy. Association between S wave in aVL resolution and all-cause hospital mortality in various subgroups of patients was estimated with Cox regression and Kaplan-Meier’s (KM) curves.

Results
S wave resolution in aVL in 48 h was recorded in 135 (63.7%) patients. Patients treated with thrombolysis had a higher frequency of S wave resolution compared to those treated with anticoagulant therapy only (76.3% vs 54.5%, p=0.01). The in-hospital mortality rate was significantly lower in patients with S wave resolution regardless of the patient sex (1.4% vs 25.8%, p&lt;0.001 in men, and 6.1% vs 34.8% in women) age (1.1% vs 31.0%, p&lt;0.01 in patients&lt;70 y, and 9.1% vs 31.4%, p&lt;0.01 in patients≥70y), thrombolytic therapy (2.9% vs 26.2%, p&lt;0.01 in patients treated with thrombolysis, and 6.2% vs 37.1%, p&lt;0.01 in patients who did not), duration of symptoms (3.0% vs 44%, p&lt;0.01 in patients with symptoms less than 24 hours, and 4.4% vs 25%, p&lt;0.01 in patients who had symptoms more than 24 hours before admission) and risk (3.2% vs 18%, p&lt;0.01 in intermediate-high risk PE, and 4.9% vs 55.6%, p&lt;0.01 in high-risk PE). KM Log Rank p for hospital survival regarding S wave aVL resolution was 0.003 for patients who did not treated with thrombolysis, and &lt;0.001 in patients treated with thrombolysis (figure 1 and 2).

Conclusion
S wave resolution in aVL in the 48 h of acute intermediate-high and high-risk PE patients is an excellent sign of improvement of right ventricle function, and it is associated with better outcomes whenever patients are treated or not with thrombolysis, or if they belong to high-risk or intermediate-high risk subgroup.KM S wave resolution and NO thrombolysisKM S wave resolution and thrombolysis
Epidemiology and management of patients with pulmonary arterial hypertension associated with congenital heart disease: data from the hellenic pulmonary hypertension registry (HOPE)
Authors: Arvanitaki A , Farmakis I , Demerouti E , Anthi A , Naka A , Brili S , Gourgiotis P , Papadopoulos G , Apostolopoulou S , Stamatopoulou V , Frogoudaki A , Frantzeskaki F , Karyofyllis P , Manginas A , Giannakoulas G 
Published: November 2023

Abstract

Background
Pulmonary arterial hypertension (PAH) is a common complication among adult patients with congenital heart disease (CHD). Since clinical trials on PAH-CHD are scarce, registry data are required to shed light on the epidemiology and management of this subgroup.

Purpose
To present "real-world" data about the epidemiology, management and long-term course of PAH-CHD from the Hellenic Pulmonary Hypertension Registry (HOPE).

Methods
The HOPE registry was launched in early 2015 and enrols patients from all pulmonary hypertension subgroups in Greece. This analysis focuses on PAH-CHD.

Results
In total, 85 PAH-CHD patients of whom 50 women (59%) have been enrolled from 8 centers between 2015 and 2022. A follow-up visit was available in 39 patients (45.8%). Median age at first visit was 37 (24, 60) years. About three quarters of patients had a pre-tricuspid (n=32, 37.6%) or a post-tricuspid shunt (n=30, 35.2%), with a quarter of patients having a complex CHD (n=21, 24.7%). Eisenmenger physiology was present in 31 patients (36.4%). The most common comorbidities at baseline were obesity (n=14, 16%), thyroid disease (n=12, 14%) and atrial fibrillation (n=12, 14%). About two thirds of patients were mildly symptomatic at baseline (NYHA I/II, n=55, 64.7%) and remained so at follow-up (n=25/39, 63.7%) with a median time of last available visit at follow-up of 1484 days (4.1 years). According to the three strata ESC risk stratification score, half of patients were at intermediate risk at baseline, while more than half of patients were at low risk for 1-year mortality at follow up (Figure 1A). More than half of patients received PAH monotherapy at baseline (n=46, 54%), with one fifth not receiving any PAH-targeted therapy (n=18, 21.2%). At 4.1 years, half of patients were on combination therapy (n=20/39, 51.3%) (Figure 1B). During a median follow up time of 2547 days (7 years), 17 deaths were reported (0.01 deaths/ patient year) (Figure 2A). 1-, 3- and 5- year survival rates were 96.4% (92.4%-100%), 88.9% (82.3%-96%), and 88.9% (82.3%-96%), respectively. Survival was better among low-risk patients at baseline, compared to moderate and high-risk ones (Figure 2B).

Conclusion
In this national cohort of ACHD PAH there was a tendency towards combination therapy at follow-up which might be the cause for reduced mortality risk. The three strata ESC risk stratification score may be a useful tool to risk assess these patients for long-term survival.Risk stratification and pharmacotherapyOveral and risk-estimated mortality
Pulmonary hypertension associated with left heart disease among hospitalized patients: analysis of the Nationwide Inpatient Sample
Authors: Farmakis I , Hobohm L , Christodoulou K C , Keller K , Schmidt K H , Valerio L , Konstantinides S , Giannakoulas G 
Published: November 2023

Abstract

Background
Pulmonary hypertension associated with left heart disease (PH-LHD) is the most prevalent PH class, however its prevalence ranges significantly across studies.

Purpose
To investigate the prevalence and prognostic influence of PH-LHD in a large nationwide sample.

Methods
Using the US Nationwide Inpatient Sample we calculated the prevalence of secondary PH across heart failure (HF) subtypes, cardiomyopathies, aortic, and mitral valve disease in hospitalized patients in 2018. In this context, we used logistic regression to assess the impact of PH on LHD, as well as to find significant contributors to in-hospital mortality in the PH-LHD population.

Results
Among 6,270,625 hospitalizations of patients with LHD, 801,535 were diagnosed with PH-LHD (12.8%). Prevalence of PH-LHD was 17.2% in HF with preserved ejection fraction (HFpEF) and 11.8% in HF with reduced ejection fraction (HFrEF). It was 16.8% in dilated cardiomyopathy, 12.6% in hypertrophic cardiomyopathy, 18.7% in mitral regurgitation, 28.5% in mitral stenosis, 13.5% in aortic stenosis, and 13.9% in aortic regurgitation hospitalizations (Figure 1). PH was associated with increased in-hospital mortality (reported odds ratios [OR] with corresponding 95% confidence intervals [CI]) in HFpEF (1.23; 1.17-1.28), hypertrophic cardiomyopathy (1.42; 1.06-1.89), mitral regurgitation (1.17; 1.07-1.28), and aortic stenosis (1.14; 1.04-1.26), but not in HFrEF (1.04; 0.99-1.10), or dilated cardiomyopathy (1.13; 0.99-1.29). Among patients with PH-LHD, significant predictors of all-cause in-hospital mortality included age, atrial fibrillation/flutter, cancer, and acute cardiac (acute right HF, myocardial infarction, ventricular arrhythmia), or extra-cardiac (stroke, sepsis, pneumonia, acute renal failure, venous thromboembolism) diagnoses (Figure 2).

Conclusion
In a nationwide analysis of hospitalized patients due to LHD the prevalence of PH was lower than previously reported indicating reduced recognition of this disease in real world clinical practice. The diagnosis of PH-LHD was associated with worse fatality rates across most forms of LHD. The findings should be further explored in future prospective studies.Figure 1Figure 2
Right heart failure as a source of B-lines at lung ultrasound: prevalence and functional correlates
Authors: D'alto M , Di Maio M , Liccardo B , Argiento P , Romeo E , Del Giudice C , Renon F , Vergara A , Di Vilio A , Caiazza E , Gargani L , Bossone E , Golino P , Picano E , Naeije R 
Published: November 2023

Abstract

Background
Lung ultrasound is part of the standard transthoracic examination and B-lines provide an index of extravascular lung water allowing to measure pulmonary congestion in left heart failure. However, pulmonary congestion can also appear as a consequence of right heart failure and it has been assumed that depends on the increase in central venous pressure increasing the resistance to lymphatic drainage. Aim of this study was to assess the prevalence of lung B-lines in a clinical model of pure right heart failure due to idiopathic pulmonary arterial hypertension (PAH) and its correlation with haemodynamic parameters.

Methods
All patients referred for suspicion of pulmonary hypertension in a single tertiary centre from January 2020 to December 2022 underwent a complete diagnostic work-up including echocardiography, lung ultrasound and right heart catheterization. The diagnosis of PAH was made following the current international recommendations. Pulmonary congestion was identified by lung ultrasound B-lines using an 8-site scan.

Results
The study enrolled 102 patients with PAH. Patients’ characteristics are shown in Table 1. The median lung B-lines were 3 [IQR: 1-5]. Results of univariate and multivariate analysis of B-lines predictors are shown in Table 1. Right atrial pressure (RAP), tricuspid annular plane excursion (TAPSE)/ Systolic pulmonary pressure (sPAP) ratio and pro hormone brain natriuretic peptide (proBNP) were independent predictors of B lines.

Conclusion
RAP, TAPSE/sPAP and proBNP were independent predictors of B lines in PAH patients according to the pathophysiological hypothesis that B-lines depends on the increase in central venous pressure increasing the resistance to lymphatic drainage.Table 1
Initial anticoagulation therapy with direct oral anticoagulants in patients with intermediate-high-risk pulmonary embolism: from the COMMAND VTE Registry-2
Authors: Shigeno R , Kim K , Chatani R , Kaneda K , Nishimoto Y , Ikeda N , Kobayashi Y , Ikeda S , Takase T , Tsuji S , Oi M , Takada T , Otsui K , Yamashita Y , Furukawa Y 
Published: November 2023

Abstract

Background
Patients with intermediate-high-risk pulmonary embolism (PE) who have both right ventricular dysfunction and elevated cardiac biomarkers are at a high risk of early hemodynamic decompensation and circulatory collapse, and it might be reasonable to treat these patients with parenteral anticoagulation therapy before switching to oral anticoagulation therapy. Recently, initial direct oral anticoagulants (DOACs) therapy in patients with PE have been shown to be non-inferior compared with initial parenteral anticoagulation therapy followed by vitamin K antagonist, which might be also a potential alternative for patients with intermediate-high-risk PE. However, the effectiveness and safety of initial DOACs therapy in this patient population have not been well investigated.

Methods
The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic venous thromboembolism (VTE) patients among 31 Japanese medical centers in the DOAC era between January 2015 and August 2020. The current study population consisted of 515 patients with intermediate-high-risk PE who were normotensive and right ventricular dysfunction on echocardiography or computed tomography, accompanied by elevated troponin levels (troponin I &gt;0.028 ng/mL or troponin T &gt;0.014 ng/mL) or N-terminal pro-B-type natriuretic peptide (NT-proBNP)/B-type natriuretic peptide (BNP) levels (NT-proBNP ≥600 pg/mL or BNP ≥100 pg/mL). The patients were divided into 2 groups; patients with initial DOACs therapy (N=107) and those with initial parenteral anticoagulation therapy (N=408).

Results
Most of baseline characteristics were comparable between the 2 groups. The 1-year cumulative incidence of bleeding events was significantly lower in patients with initial DOACs therapy than in those with initial parenteral anticoagulation therapy (6.5% vs. 15.3%, P=0.007) (Figure 1A), whereas the 1-year cumulative incidence of VTE recurrence was comparable between the 2 groups (2.2% vs. 2.2%, P=0.62) (Figure 1B). The 1-year incidence of all-cause mortality was numerically lower in patients with initial DOACs therapy than in those with initial parenteral anticoagulation therapy without statistically significant difference (4.5% vs. 13.5%, P=0.06) (Figure 1C).

Conclusions
Initial DOACs therapy in patients with intermediate-high-risk PE showed no signal of worse outcomes compared with initial parenteral anticoagulation therapy, which could be a potential initial anticoagulation strategy in this patient population.Figure 1
Chronic thromboembolic disease is associated with exercise-induced pulmonary hypertension and functional right ventricle deterioration
Authors: Madonna R , Morganti R , Badagliacca R , Biondi F , Alberti M , Vizza C D , De Caterina R 
Published: November 2023

Abstract

Background and Aim
Chronic thromboembolic pulmonary disease (CTED) is a progressive disease caused by a wall-adherent, fibrotic thrombus in the pulmonary circulation persisting despite oral anticoagulation and despite vascular remodeling of the small arteries. Despite normal pulmonary hemodynamics at rest, exercise intolerance and dyspnea have been reported. Drivers and risk factors, as well as the clinical impact of CTED, are not yet adequately characterized. We evaluated clinical factors predictive of the development of postthrombotic pulmonary disease in a cohort of patients with a history of acute pulmonary embolism on oral anticoagulant therapy. We also evaluated its impact on functional capacity, pulmonary haemodinamics at rest and after exercise and right ventricle morphology and function.

Methods
We compared 33 consecutive patients with a history of acute pulmonary embolism and normal pulmonary vascular imaging (group 1, n=16) or persistent defects on perfusion scan (positive P scan) despite therapeutic anticoagulation for 4 months (group 2, n=17), for the following parameters: 1. Thrombotic load (extension of pulmonary thromboembolism on CT angiography) and Pulmonary Embolism Severity Index (PESI) score at the time of admission to the Intensive Care Unit (ICU); 2. Presence of thrombophilia (factor V Leiden, prothrombin variant, lupus anticoagulant); 3. Cardiovascular risk factors; 4. Anthropometric and demographic parameters; 5. Anticoagulation treatment in ICU and at discharge. The two groups of patients were also compared for the World Health Organization functional class (WHO-FC), NT-proBNP, cardiopulmonary exercise test (CPET) and echocardiographic parameters at rest and after exercise (ESE), at 4 and after 24 months.

Results
Compared with group 1, patients with persisting perfusion defects (group 2) featured higher thrombotic load (p=0.004) and PESI score (p=0.02) at the time of ICU admission. At 4 months, group 2 developed exercise-induced pulmonary hypertension (Ex-PH) at CPET (p&lt;0.001) and ESE (p&lt;0.001). At the 24 months follow-up group 2 showed higher NT-proBNP (p&lt;0.001) and WHO-FC (p&lt;0.001), systolic (p&lt;0.001) and diastolic (p=0.037) right ventricular (RV) dysfunction and worse echo indices of RV-Arterial Coupling (TAPSE/PAPs (p&lt;0.001)), despite maintaining a low or intermediate echocardiographic probability of PH (Table 1).

Conclusions
Despite the low and intermediate echocardiographic probability of PH, patients with persistent positive P scan had reduced functional capacity, and developed ExPH and RV functional deterioration.