bluuebunny/crossref_metadata_2025 huggingface dataset:
Recruitment of CCR5-positive T cells in pulmonary vascular lesions in idiopathic- and connective tissue disease associated- pulmonary arterial hypertension
Authors: Ohta-Ogo K , Ishibashi-Ueda H , Ogo T , Ikeda Y , Inagaki T , Matsumoto M , Amemiya K , Nakaoka Y , Hatakeyama K
Published: October 2024

Background

C-C chemokine receptor type 5 (CCR5) is a chemokine receptor predominantly expressed on leukocytes including T cells, macrophages, and dendritic cells, and is involved in the process by which T cells are attracted to specific tissues and organs. Although CCR5 has been shown to be expressed on macrophages and pulmonary artery smooth muscle cells in lung samples from human idiopathic pulmonary arterial hypertension (PAH) and some animal models, its expression on T cells in human PAH lungs has not been investigated.

Purpose

To investigate the immunohistochemical expression of CCR5 on T cells infiltrating in pulmonary vascular lesions of human PAH tissues, particularly from patients with idiopathic PAH and PAH associated with connective tissue disease (CTD-PAH), where inflammation has been implicated in the pathogenesis.

Methods

Subjects included 25 postmortem cases of idiopathic PAH (14 cases, a mean age of 34 ± 10 years, 8 female cases) and CTD-PAH (11 cases, 48 ± 13 years, all female). We performed immunohistochemistry using antibodies against CCR5 and CD3 (for T cells) on formalin-fixed paraffin-embedded sections. To semi-quantify, we selected the three small muscular pulmonary arteries (80-150 µm in external diameter) with the strongest CCR5-positive cell infiltration in each case, counted the number of positive cells, and the average were shown as the number of cells per vessel.

Results

In all cases, regardless of whether IPAH or CTD-PAH, a subset of infiltrating inflammatory cells into or accumulating around vessels was CCR5-positive. Specifically, CCR5-positive inflammatory cells were found in remodelled pulmonary arteries, such as plexiform lesions and constrictive lesions with intimal thickening and/or medial hypertrophy, as well as perivascular space. The average number of CCR5-positive cells per small muscular pulmonary artery was 8.1/vessel. Where pulmonary venous occlusive lesions were seen, CCR5-positive cells were also present in and around them. The majority of CCR5-positive inflammatory cells appeared to be T cells, based on morphology and CD3 immunopositivity in the serial sections.

Conclusion(s)

Activated T cells showing CCR5 immunopositivity were recruited to remodelled pulmonary vascular lesions in both idiopathic PAH and CTD-PAH. This implicates CCR5-positive T cells as a common key player and that CCR5 signalling is involved in the pathogenesis of PAH in concert with other inflammatory cells, vascular endothelial cells, and pulmonary artery smooth muscle cells.
Epidemiology of acute pulmonary embolism in children and adolescents from nationwide US hospital data, 2016 and 2019
Authors: Wolf S , Valerio L , Kucher N , Konstantinides S , Klok F A , Cannegieter S C , Barco S
Published: October 2024

Background

Data on the epidemiological burden and comorbidities associated with pulmonary embolism (PE) in children and adolescents is sparse.

Purpose

We aimed to describe the burden of acute PE in children by estimating indicators of incidence and mortality as well as the prevalence of key comorbidities in hospitalized children with (vs. without) PE.

Material and methods

We did a patient-level analysis of the United States Kids' Inpatient Database (KID), including patients aged 0 to 19,cumulatively for the years 2016 and 2019. PE was defined by the ICD-10 Code I26. We calculated annualized, nationwide, age-sex-specific incidence rate, mortality rate, case mortality rate, and proportionate mortality rate. Additionally, we studied the prevalence of 120 clinically selected disorders in children with vs. without acute PE.

Results

Acute PE was recorded in 5,738 cases (58.6% female). A total of 244 (4.3%) patients were aged 0, 214 (3.7%) aged 1-4, 206 (3.6%) aged 5-9, 677 (11.8%) aged 10-14, and 4,392 (76.5%) aged 15-19 years. The incidence rate of PE shows a J-shape curve increasing with increasing age. Proportional mortality rate paralleled the incidence rate peaking at 9.5 (95% CI: 7.3-12.3) deaths per 1,000 deaths for girls and 5.0 (4.0-6.2) deaths per 1,000 deaths for boys aged 15-19 years. In contrast, case mortality rate decreased from 33% (95% CI: 24.8-42.4) among girls and 15.9% (95% CI: 10.8-23) among boys in the first year of age to 2.1% (95% CI: 1.6-2.7) among girls and 4.5% (95% CI: 3.6-5.6) among boys aged 15-19. Table 1 presents key age-sex stratified epidemiologic indicators. The highest absolute prevalence difference (APD) between those with vs. without PE was found for venous thrombosis (APD: 31.8%, 95% CI: 30.6-33), followed by metabolic disorders (APD: 15.2%, 95% CI: 14-16.5) and obesity (APD: 14.7%, 95% CI: 13.7-15.8). Figure 1 presents an overview of the APD of clinically selected disorders in patients with vs. without PE.

Conclusion

This comprehensive overview shows that the burden of PE among children and adolescents is considerable, but with considerable variation across age classes and co-occurrence with different specific comorbidities.Table 1.Figure 1.
Diagnosis of chronic thromboembolic pulmonary disease from an intensive pulmonary embolism treatment center
Authors: Sato M , Ikeda N , Hayashi F , Niikura H , Iijima R , Hara H , Nakamura M
Published: October 2024

Background

The diagnosis of Chronic Thromboembolic Pulmonary Disease (CTEPD) following an episode of acute pulmonary embolism (PE) has exhibited inconsistencies across different healthcare institutions, and the issue of underdiagnosis remains unresolved.

Purpose

The aim of this study is to ascertain the incidence of CTEPD following an episode of acute PE through a follow-up conducted at a specialized PE outpatient clinic located within a PE expert center.

Methods and Results

In this retrospective study, a cohort of 106 consecutive patients (mean age: 63.7±17.5 years, female: 51.9%) diagnosed with acute PE between March 2015 and August 2020 at our hospital were included. Patients who were capable of visiting the hospital received follow-up care at an outpatient clinic specializing in PE. The diagnosis of CTEPD was established in cases where patients, regardless of the presence of pulmonary hypertension, exhibited chronic-phase dyspnea and demonstrated perfusion defects on lung perfusion scintigraphy. Furthermore, individuals with a mean pulmonary arterial pressure ≥25 mmHg and a pulmonary capillary wedge pressure ≤15 mmHg, as determined by right heart catheterization, were diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH). During the follow-up period (median duration: 27.5 months), 23 patients were diagnosed with CTEPD, and 10 patients were diagnosed with CTEPH. The cumulative incidence rates of CTEPD and CTEPH were as follows: 20.8% and 10.8% at 1 year, 26.9% and 12.7% at 2 years, respectively; and 28.9% at 3 years for CTEPD. Signs of RV dysfunction on CT or Echocardiography may have contributed to the detection of CTEPH and were discussed with respect to parameters indicating RVdisfunction.

Conclusions

In present study, the cumulative incidence of CTEPD and CTEPH is notably elevated. This results suggest that active surveillance after acute PE follow-up practices may have contributed to an enhanced rate of diagnosis or that chronic PE or CTEPH may have been included at the time of PE diagnosis.Cumulative Incidence of CTEPDCumulative Incidence of CTEPH
TAPSE/sPAP by echocardiography to detect elevated pulmonary vascular resistance> 4 WU in postcapillary pulmonary hypertension patients: insights from the French PH HF registry
Authors: Bauer F , Berthelot E , Eicher J C , Trochu J N , Habib G , Isnard R , Lamblin N
Published: October 2024

Background

Post-capillary pulmonary hypertension (pcPH) lacks effective treatment options. Patients with a PVR > 4 WU, known as combined pcPH (cpcPH), may benefit from investigational drugs like sotatercept. Identifying cpcPH patients suitable for vasodilation therapy in echocardiography labs is critical.

Purpose

To pinpoint an echocardiographic parameter capable of detecting cpcPH patients with a PVR above 4WU, addressing a common challenge in clinical practice.

Methods

In this study, 225 participants from the French PH-HF registry, all diagnosed with heart failure and a preserved ejection fraction, were examined. These patients underwent right heart catheterization and got ultrasound examinations within a 24-hour timeframe. The pulmonary vascular resistance were calculated using previously established methods, and data from standard echocardiography, including assessments of diastolic function, were gathered.

Results

69 patients exhibited a pulmonary vascular resistance (PVR) greater than 4 WU, while 156 patients had a PVR ≤ 4 WU. Age averaged 69±12 years. Mean pulmonary artery pressure, wedge pressure, cardiac output, and pulmonary vascular resistance were 39±9 mm Hg, 22±4 mm Hg, 5.1±1.7 l/min, and 3.5±2.0 WU, respectively. Comparative analysis between patients with PVR ≤ 4 WU and those with PVR > 4 WU revealed similar ejection fraction (EF), left atrial volume index, and E/A ratio by echocardiography (p=0.97, p=0.69, p=0.43, respectively). However, patients with PVR > 4 WU showed elevated E/e’ (p=0.008), higher systolic pulmonary artery pressure (sPAP, p=0.001), but reduced myocardial S and e’ tissue Doppler velocities (p=0.001) and tricuspid annular plane systolic excursion (TAPSE) (p=10^-5). Notably, the relationship between TAPSE/sPAP and PVR > 4 was curvilinear and strong (p=0.001, FIG 1). Using ROC curve analysis, patients with TAPSE/sPAP < 0.38 mm/mmHg were identified to have PVR > 4 WU with a sensitivity and specificity of 68%.

Conclusion

Within the scope of postcapillary pulmonary hypertension, right ventricular arterial coupling is a simple ultrasound parameter potentially effective in identifying individuals exhbiting PVR > 4 WU with a good sensitivityFigure 1:PRV and coupling plotFigure 2:RV coupling ROC
Effects of beta blockers on outcome in patients with PAH with and without comorbid conditions: a Multicenter Prospective Cohort Study (BNP-PL)
Authors: Waligora M , Kurzyna M , Mularek-Kubzdela T , Skoczylas I , Chrzanowski L , Blaszczak P , Jaguszewski M , Kusmierczyk B , Ptaszynska-Kopczynska K , Grzesk G , Mizia-Stec K , Doboszynska A , Peregud-Pogorzelska M , Lewicka E , Kopec G
Published: October 2024

Background

The current guidelines do not recommend the use of beta-blockers (BB) in patients with pulmonary arterial hypertension (PAH) unless necessitated by comorbidities. However, the evidence regarding the role of BB in PAH is contradictory. This study investigates the effects of BB on clinical outcomes in patients newly diagnosed with PAH, stratified by the presence of cardiovascular comorbidities that justify their use.

Methods

We analyzed data from 806 patients newly diagnosed with PAH, who were prospectively enrolled from March 1, 2018, to August 31, 2023, in the multicentre registry, Database of Pulmonary Hypertension in the Polish population (BNP-PL). The primary endpoints were all-cause mortality and a composite of hospitalization due to right heart exacerbation, syncope, or death. The follow-up period for these patients extended until August 31, 2023. Comorbidities in the study group that indicated the need for BB therapy included hypertension, significant arrhythmia, and coronary artery disease. In the Cox regression analysis, the association between BB use and the predefined endpoints was adjusted for age, baseline European Society of Cardiology risk score, and upfront therapy.

Results

Among the 806 patients, BBs were administered to 469 (58.2%) at the time of PAH diagnosis. In the entire cohort, BB therapy was linked to increased all-cause mortality (29.6% vs 21.4%; p=0.005, Fig 1.A) and a higher incidence of the composite endpoint (34.1% vs 22.6%; p<0.0001, Fig 1.B). The Number Needed to Harm (NNH) for BB treatment, regarding mortality and the composite endpoint, were 12.1 and 8.7, respectively. In patients without comorbidities, BB use significantly raised the risk of both all-cause mortality (Hazard Ratio [HR] 1.81, 95% Confidence Interval [CI]: 1.01-3.15) and the composite endpoint (HR 1.85, 95% CI 1.09-3.14), after adjustments for age, baseline three-strata PAH mortality risk, and upfront therapy. However, in patients with at least one comorbidity, BB therapy showed a neutral effect on both outcomes. Across the whole group, the use of nonselective BB was associated with a higher risk of the composite endpoint (HR 1.78, 95% CI 1.13-2.82, p=0.01) compared to selective β1 agents, although this did not extend to all-cause mortality (HR 1.34, 95% CI 0.79-2.25, p=0.28).

Conclusion

BBs, particularly nonselective, pose significant risks in patients with PAH who lack comorbidities that justify their use.
Comparison of ultrasound-assisted thrombolysis and mechanical thrombectomy in patients with intermediate-high-risk pulmonary embolism
Authors: Pinsdorf D , Knuschke R , Petrikhovich O , Messiha D , Janosi A , Rassaf T , Rammos C
Published: October 2024

Background

Pulmonary embolism (PE) can cause right heart failure and is associated with a high mortality. Early risk stratification is critical for individualized management. In patients with intermediate-high-risk PE, guidelines recommend to consider a percutaneous catheter-directed treatment (CDT). While different techniques are available, comparisons between treatments regarding right heart function and outcome are still scarce.

Purpose

To compare changes in right heart function as well as outcome in patients with intermediate-high-risk PE after catheter-directed treatment with ultrasound-assisted thrombolysis as compared to mechanical thrombectomy.

Methods

This is a retrospective, single-center study in intermediate-high-risk PE. According to the ESC guidelines, all patients had PESI class III-V, RV dysfunction and elevated cardiac troponin levels, but were hemodynamically stable. PE was confirmed by CT angiography. All patients underwent a catheter-directed treatment. One group received an ultrasound-assisted thrombolysis (USAT), while the other had a large-bore mechanical thrombectomy (MT). Right heart function (RV-Diameter, RV-/LV-Ratio, TAPSE) assessed via transthoracic echocardiography before and after CDT as well as interventional characteristics and postinterventional hospital stay were compared.

Results

From June 2022 to January 2024, 27 patients (43% female; aged 62 ± 14 years) were diagnosed with pulmonary embolism with intermediate-high-risk and underwent a catheter-directed treatment. Most patients (89%) had bilateral pulmonary embolisms. 15 patients (55%) received an ultrasound-assisted thrombolysis. 12 patients (45%) had a mechanical thrombectomy via a large-bore aspiration system. The mean procedural time was 41 ± 19 minutes for USAT and 106 ± 33 minutes for MT (p < 0.001). Right ventricular / left ventricular ratio reduction was -0.48 ± 0.25 in the USAT group (p < 0.001) and -0.34 ± 0.14 in the MT group (p < 0.001) (between group difference p = 0.2). TAPSE increased by 8 mm ± 4.4 mm in the USAT group (p < 0.001) and by 8.7mm ± 3.8 mm in the MT group (p < 0.001) (between group difference p = 0.7). The median postinterventional hospital stay was 7 days for the USAT patients and 7 days for the MT patients (between group difference p = 1).

Conclusions

In patients with intermediate-high-risk PE both ultrasound-assisted thrombolysis and large-bore mechanical thrombectomy lead to an improved right heart function with both interventions leading to a similar length of postprocedural hospital stay. Further randomized data have to discriminate differential impact of novel tools for the treatment of intermediate risk PE.
Evaluation of naples prognostic score to predict long-term mortality in patients with pulmonary embolism
Authors: Pay L , Cetin T , Keskin K , Dereli Ş , Tezen O , Yumurtas A , Kolak Z , Eren S , Saylik F , Cinar T , Hayiroglu M
Published: October 2024

Background/Introduction

APE mortality rates are still not satisfactory despite new diagnosis and treatment methods (1). Thus, risk classification is crucial due to the wide range of clinical presentations. Several risk stratifications have been developed such as simplified Pulmonary Embolism Severity Index (sPESI) (2). Nonetheless, there remains a need for an optimal indicator that can be conveniently measured with a high degree of precision to predict clinical outcomes. Naples prognostic score (NPS) is a newly defined index that is developed to determine the prognosis of cancer patients and reflects the inflammatory and nutritional status of the patients (3).

Purpose

The aim of our study was to determine the long-term prognostic value of NPS in APE patients.

Methods

Two hundred ninety-three patients diagnosed with APE between November 2016 and February 2022 were included in the study. NPS consists of 4 parameters: serum albumin, total cholesterol (TC) concentration, neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR). Naples scores of all patients were calculated and the patients were divided into 2 groups according to their NPS and their long-term mortality was compared. The primary endpoint of the study was long-term mortality.

Results

The long-term mortality was observed in 38 patients out of 293 patients in the mean follow-up of 24 (16-42) months. In the low-Naples risk group (group 1), there were 215 patients, while the high-Naples risk group (group 2) had 78 patients. Multivariate analysis showed that NPS as a categorical parameter (HR: 3.458, 95%CI:1.734-6.896, p<0.001), NPS as a numerical parameter, (HR:1.651, 95%CI:1.217-2.241, p=0.001) and simplified pulmonary embolism severity index (sPESI) (HR:1.887, 95%CI:1.223-2.911), p=0.004) score were independent predictors of long-term mortality. The receiver operating characteristic curve analysis showed that the model 2 with NPS as continuous had higher discriminative ability than the baseline model for detecting patients with mortality (Area under curve (AUC) values = 0.791 vs. 0.723, respectively, p=0.04) (Figure 1A). The long-term predictive capability of NPS was non-inferior than the sPESI score (Figure 1B).

Conclusions

The current study highlights that NPS, which reflects systemic inflammation and nutritional status may have potential to predict long-term mortality in APE patients. To our knowledge, this is the first study to show the relationship between long-term mortality and NPS in APE patients.
Right ventricular dysfunction parameters at echocardiography in patients with acute pulmonary embolism: meta-analysis of individual participant data
Authors: Cimini L A , Pruszczyk P , Jimenez D , Weekes A , Zuin M , Vanni S , Ciurzynski M , Kostrubiec M , Khemasuwan D , Yuriditsky Y , Bahloul M , Rajagopal S , Pieralli F , Monreal M , Becattini C
Published: October 2024

Background & Aim

Echocardiography has a crucial role for decision making on management of patient with acute pulmonary embolism (PE) according to current international guidelines. However, the definition of right ventricle dysfunction (RVD) at echocardiography requires standardization. We performed an Individual patient data meta-analysis (IPDMA) to assess the role of individual parameters of RVD and of combinations of parameters for the prediction of short-term all-cause mortality and PE-related death.

Methods

A systematic search was run to identify clinical studies reporting on RVD at echocardiography and on short-term clinical outcome in patients with acute PE. Individual patient data from the original studies were pooled to perform a meta-analysis (IPDMA). The study outcomes were short-term death defined as death occurring within 30 days from PE diagnosis and PE-related death. Multiple imputation was used for the management of missing data. The odds ratio for all cause and PE related mortality were calculated using generalized linear mixed effects model.

Results

Individual data from 9,233 patients with acute PE from 16 studies were pooled in a unique database. All cause short-term mortality occurred in 9% of patients (95% CI 0.06-0.13, I2 93%). The IPDMA was feasible for the following parameters: tricuspid anulus systolic excursion (TAPSE), estimated pulmonary artery pressure (PAP) >30mmHg, right to left ventricle diameter ratio (RV/LV)>1, hypokinesia, paradoxical septal motion, RV diameter>30 mm and McConnel sign. All these parameters, except for PAP>30mmHg and RV diameter>30 mm, were predictors of short-term all cause death in the overall population and in hemodynamically patients (table). All the assessed RV findings, except for the McConnell’s sign, were predictors of PE-related death (Table). The presence of one RVD parameter only was not associated with increased risk of all cause death (OR 1.22, 95% CI 0.97-1-54), while the presence of two parameters or ≥ three parameters were (OR 1.63, 95% CI 1.24-2.15; OR 2.07 95% CI 1.59-2.69, respectively).

Conclusion

In patients with acute PE, the majority of RVD parameter at echocardiography are predictors of short-term death and of PE-related death. The higher the number of RVD parameters the worst the prognosis. These results claim for standardization in RVD definition to guide decision making for patient management.
A novel dynamic risk score to predict venous thromboembolism (VTE) recurrences after 3 months of anticoagulation in patients with incident VTE and without active cancer
Authors: Cohen A , Choudhuri S , Khan I , Pollock K , Bober-Irizar M , Galias Z , Irizar A , Bober M
Published: October 2024

Background

Predicting the risk of recurrent venous thromboembolism (rVTE) during and following anticoagulation is complex. Current models lack the ability to adapt to changing patient conditions over time and fail to account for the direct impact of anticoagulation in real-world clinical settings.

Purpose

To develop a dynamic risk prediction model for rVTE to help clinicians decide on the duration of anticoagulant therapy in conjunction with a model for bleeding (also submitted to the conference).

Methods

UK Clinical Practice Research Datalink data (2001-2020) was used to generate a retrospective cohort with first VTE who had received 3 months of anticoagulation. Patient episodes of rVTE were evaluated. Covariates were collected at baseline and subsequently as time-varying data to capture changes post-VTE. Hazards with 95% confidence intervals (CI) were estimated and covariates included in a Fine & Gray model used as predictors of rVTE. An additive (logarithmic) scoring scheme was developed from subdistribution hazard ratios, discrimination (expressed by the C-statistic) estimated from 10-fold cross-validation.

Results

51,465 patients with a first VTE were included; 4041 rVTE were identified in 200,698 person-years of observation. Incidence rates for rVTE were 2.01 per 100 person-years. Nineteen independent predictors of rVTE (recorded before or after the VTE diagnosis) were included in the model, 13 associated with increased risk and 6 with decreased risk, Table 1. Patients recognised as lower-risk, medium and higher-risk (10.5%, 37% and 52.5% of the population, respectively, at 90 days after first VTE, assuming no anticoagulation treatment) had an annualised rVTE incidence rate of 2.20, 3.84, and 7.44 per 100 person-years. The C-statistic for rVTE was 0.65 (95%CI, 0.64-0.66). The points scored can be added or subtracted to predict risk (Table 2).

Conclusions

Our dynamic risk score effectively identifies patients at risk of rVTE three months post their initial VTE diagnosis. It allows for continuous monitoring of risk, and modelling of treatment impact, providing clinicians with a pragmatic tool to help determine treatment duration, and adapt their strategies in response to evolving patient conditions.Table 1:Predictors for VTE recurrenceTable 2:VTE recurrence risk score
Mini nutritional assessment is a predictor of mortality and morbidity in patients with pulmonary arterial hypertension
Authors: Wieteska-Milek M , Szmit S , Florczyk M , Betkier-Lipinska K , Kusmierczyk-Droszcz B , Zielinski P , Krzesinski P , Hoffman P , Kurzyna M
Published: October 2024

Background

Malnutrition has been demonstrated as a predictor for unfavorable clinical outcomes in chronic heart failure, and may affect patients with pulmonary arterial hypertension (PAH). The Mini Nutritional Assessment (MNA) is a reliable indicator for nutritional status assessment, but its relationship with mortality risk and hospitalization in PAH patients has not yet been investigated.

Purpose

The study aimed to determine whether the MNA has prognostic value in stable patients with PAH.

Methods

A prospective multicenter study was performed. All patients completed the MNA at study entry in outpatient clinic or during planned hospitalization. The primary endpoint was all-cause mortality. Secondary end-point was the composite end-point of all cause death or PAH-related hospitalizations. Patients with malnutrition (MNA ≤17 points) or at risk of malnutrition (MNA 18-23,5 points) were considered as having abnormal nutritional status for statistical analysis.

Results

182 PAH patients were included to the study (mean age 60 ± 17 years; 73% females; 57% idiopathic PAH). Abnormal nutritional status was identified in 68 (37%) patients. Median and the range of follow up period was 23 months and 0–32 months, respectively. 34 (18.7%) patients died, 53 (29.1%) were hospitalized due to PH, and 57 (31.3%) achieved the composite secondary end-point.

Kaplan-Meier survival curves revealed significant differences in overall survival between patients with abnormal MNA and normal MNA, p <0.0001, and significant differences in composite risk of death and PAH-related hospitalization, p=0.02.

In the multivariate Cox regression analysis including age, sex, and main risk factors (COMPERA 2.0 score, TAPSE/PASP, right atrial pressure, cardiac index, mix oxygen saturation), abnormal MNA remained significantly associated with all-cause mortality (HR 2.86 [95%CI: 1.29–6.38], p=0.01) and the composite end-point HR 2.39 [95% CI: 1.05–5.42], p=0.04) in PAH patients.

Conclusions

Using MNA as a routine screening tool allowed the detection of abnormal nutritional status in more than one third of PAH patients. Nutritional status assessed by the MNA was an independent predictor of all-cause death and the composite end-point of all-cause death and PAH-related hospitalization in patients with PAH.
Improved prognosis prediction of idiopathic pulmonary arterial hypertension using targeted plasma proteomics in disease management
Authors: Yang Y , Shu S R , Sun B , Wang P Z , Zeng Q X , Wang C S , Xiong C M
Published: October 2024

Background

Idiopathic pulmonary arterial hypertension (IPAH), a special subgroup of PAH with unclear etiology, is characterized by rapid progression and poor prognosis underscoring the need for optimization of IPAH management and the accurate prediction of prognosis. However, it is disappointing that specific plasma biomarkers for IPAH management and prognosis are lacking in clinical practice. Up to date, the plasma biomarkers used for assessment of IPAH severity and prognosis are relied solely on indicators such as N-terminal prohormone of brain natriuretic peptide, or brain natriuretic peptide, which could reflect cardiac function but fail to promptly response to the dynamic change of disease condition due to the complexity of IPAH pathogenesis.

Purpose

We evaluated the prognostic value of plasma proteins in addition to current clinical predictors for prognosis prediction of IPAH.

Methods

Olink Immune-Response panel was used to measure 92 plasma proteins in a prospective IPAH cohort with 169 patients and a mean follow-up period of 2.4 ± 0.9 years. Six machine learning methods were used to construct predictive models, including plasma proteins-based Olink models, clinical parameters-based clinical models, and integrative models.

Results

A total of 18 proteins showed differential expression between patients with or without adverse clinical outcomes. Three proteins (STC1, CXADR, and IL6) were strongly correlated with clinical indicators of IPAH severity and their concentrations showed upward trends along with increased risk stratification. Elevated levels of STC1, CXADR, and IL6 are all associated with an increased risk of adverse clinical events, indicated by survival analysis, restricted cubic splines, and multivariable Cox regression analysis (STC1 HR=3.474, 95%CI: 1.129-10.692, P=0.030; CXADR: HR=1.602, 95%CI: 1.074-2.387, P=0.021; IL6: HR=1.883, 95%CI: 1.376-2.576, P<0.001). The inclusion of these three proteins into the predictive model could significantly increase the predictive power on the basis of the clinical model (AUC: 0.746 vs 0.626).

Conclusions

High levels of STC1, CXADR, and IL6 in plasma were associated with severe clinical phenotype and increased risk of adverse clinical events in patients with IPAH. These plasma proteins could significantly improve the prognostic performance of pre-existing clinical models, facilitating the clinical management of IPAH patients.The predictive efficient of models
Genome wide association studies on three-dimensional aortic geometric indices measured with magnetic resonance imaging
Authors: Beeche C , Dib M J , Azzo J D , Maynard H , Salman O , Witschey W , Chirinos J
Published: October 2024

Introduction

To date, three-dimensional properties of the aorta have not been comprehensively quantified in a population level dataset, nor has there been a genome-wide association study (GWAS) to identify significant single nucleotide polymorphisms (SNPs) associated with geometric properties of the aorta.

Methods

We segmented the thoracic aorta of 48,045 subjects in the UK Biobank using a U-Net convolutional neural network. We then computed geometric measurements (centerline length, arch height, arch width, arch height-width ratio, curvature, and mean, minimum and maximum diameter) across six subsegments of the aorta. Centerline length was allometrically indexed to body height. Using generalized linear models, we performed GWAS on each geometric phenotype adjusted for the following covariates: (1) age, (2) sex, and (3) ten genetic principal components. SNPs with a minor allele frequency < 0.05 were excluded. We performed LD-based clumping with an r2 threshold of 0.001 to identify significant loci and used LDSC to compute the genetic heritability of each geometric phenotype.

Results

After performing LD clumping, we identified 457 significant(P<5e-8) SNPs across 36 aortic geometric parameters. GWAS-based heritability analyses showed a mean heritability of 13.8 (9.9) % across all aortic geometric parameters, with all intercepts being close to 1, suggesting minimal genomic inflation. Maximum aorta diameter exhibited the highest observed heritability of 34.5 (3.0) %. Allometric centerline length showed a heritability of 13.6 (1.5) %. Similarly, arch height and width showed heritability of 14.6 (1.5) %, and 13.64 (1.5) % respectively. Aortic curvature showed limited heritability at 8.54 (1.2) %, with arch curvature being further reduced to 7.6 (1.20) %.

Conclusion

To our knowledge, this was the first study that investigated the genetic architecture of aortic centerline length, aortic curvature, and aortic tortuosity. These results suggest that aortic remodeling associated with aging and pathological conditions has important genetic contributions. SNPs associated with aortic geometry may identify therapeutic targets to prevent aortic remodeling, which should be the focus of future work.significant_snpsheritability
Efficacy of beta blockers in patients with thoracic aortic aneurysm: meta-analysis of randomized controlled trials
Authors: Tanriverdi L H , Barrett A , Kalyanasundaram A , Zafar M A , Ziganshin B A , Elefteriades J A
Published: October 2024

Studies investigating the efficacy of β-blocker agents on patients with thoracic aortic aneurysm have produced heterogeneous and conflicting results. This study was aimed to assess protective effects of β-blockers in terms of aortic events (dissection, rupture) and mortality in patients with thoracic aortic aneurysm. A systematic literature search was performed through Ovid MEDLINE, EMBASE, Web of Science, Pubmed and The Cochrane Central Register of Controlled Trials (Cochrane CENTRAL), all from inception to May 10, 2022. Randomized controlled trials exploring the efficacy of β-blocker agents in patients with thoracic aortic aneurysm were considered for inclusion with no population restriction. Two independent reviewers performed the literature search. Two reviewers independently extracted all available prespecified relevant data in accordance with the International Prospective Register of Systematic Reviews protocol. Summary effect measures of the primary outcomes were obtained by pooling the data with an inverse variance–weighted random-effects model. The overall risk of bias assessment was conducted by using the Cochrane Risk of Bias 2 tool A sensitivity analysis was performed regarding whether the conclusions reached might differ substantially if a single study was omitted. The primary outcome was aortic events (aortic dissection/rupture). Secondary outcomes were death (all-cause mortality) and aortic dissection. Two independent reviewers identified 4 RCTs presented in 5 reports from 1494 unique studies screened. Three trials involving 129 eligible participants compared β blockers (propranolol and celiprolol) with no treatment. One trial involving 32 eligible participants compared β blocker (atenolol) with placebo. This systematic review and meta-analysis included 161 patients with thoracic aortic aneurysm (mean age, 27.6 years; 80 [49.7%] male, mean follow-up 6.7 years). The pooled risk ratio in the β-blocker arm for aortic events was 0.74 [95% CI (0.20; 2.71), I2: 0%, p=0.64] when comparing to the placebo or no treatment in patients with thoracic aortic aneurysm. The pooled risk ratio for death (all-cause mortality) and aortic dissection in the β-blocker arm were 0.45 [95% CI (0.10; 1.98), I2: 0%, p=0.29] and 0.58 [95% CI (0.15; 2.24), I2: 0%, p=0.43], respectively. The risk of aortic dissection, rupture, or death were essentially identical, regardless of treatment group and subgroup analysis. A sensitivity analysis revealed that none of the studies significantly influenced the pooled risk estimate to any great extent. We found no evidence of benefit from β-blocker treatment. More robust data regarding β-blocker use in patients with thoracic aortic aneurysms from randomized controlled trials are needed to establish evidence based recommendations and to determine whether current evidence comes from absense of evidence or evidence of absense.Forest plot for death (all-cause)
Impact of comorbid coronary artery disease on short and medium-term outcomes after carotid artery stenting
Authors: Resende B L , Carlos T , Fernandes R , Costa G , Batista G , Rocha L , Grine M , Simoes M , Silva A L , Guimaraes J , Santos T , Monteiro E , Lopes V , Gameiro J , Goncalves L
Published: October 2024

Background

Current recommendations acknowledge carotid artery disease as a clinical criteria for very high cardiovascular risk and carotid artery stenting (CAS) as one of the main therapeutic options for carotid artery stenosis. Carotid artery disease is often present in patients with coronary artery disease (CAD), presumably enhancing the cardiovascular risk of these patients. In this study, we aimed to appraise the prevalence and prognostic effects of comorbid CAD diagnosis in patients with significant carotid artery disease undergoing CAS.

Methods

We conducted a single-center retrospective analysis including consecutive patients that underwent CAS, between January 2007 and August 2023. Our main objective was to analyze the association of comorbid CAD in patients undergoing CAS, regarding 30-day major adverse cardiovascular events (MACE), 30-day global mortality, 1-year global mortality and major periprocedural complications. On a second perspective, we strived to identify if there was any modifiable factor that influenced worse outcomes in these populations, addressed by a Chi-Square Test. Data was collected by the medical team in our Centre, over the years of follow-up.

Results

A total of 380 patients were enrolled in this study, with a mean age of 72.1±8.3 years and no major differences concerning demographic characteristics. Based on the presence of previous CAD diagnosis, there was no statistical significance in 30-days MACE (p=0.442), 30-days global mortality (p=0.161), 1-year mortality (p=0.658) or periprocedural complications (p=0.062). Despite these results, there was a statistically significant difference in individuals with CAD and comorbid hypertension in 30-days CV death (p=0.002), 30-days global mortality (p=0.007) and 1-year global mortality (p=0.036).

Conclusions

Comorbid CAD in patients undergoing CAS due to carotid stenosis does not seem to be significantly associated with medium-term adverse events. Nevertheless, the results of this casuistry support the importance of rigorous blood pressure control in patients with significant carotid artery disease.Baseline CharacteristicsStudy outcomes
Sex differences in aortic prognosis in Marfan patients, a retrospective longitudinal study from the REPAG registry
Authors: Teixido Tura G , Domingo D , Garcia Orta R , Calvo F , Valera F , Larranaga J M , Martinez D , Badia C , Sanchez R , Sabate A , Palomino J , Limeres J , Moreno E , Forteza A , Cabrera F
Published: October 2024

Introduction

Previous studies(1-4) have suggested a more favourable aortic outcome among women with Marfan syndrome (MFS), although the precise underlying mechanism remains not completely understood. In this retrospective longitudinal study, we aim to evaluate sex differences in aortic events in a large cohort of Marfan patients seen in 11 tertiary centres in Spain.

Methods

Patients with diagnosis of Marfan syndrome (MFS) were included. Data on aortic events (AE) including elective aortic surgeries, acute aortic syndrome or death were incorporated. Survival free of the combined endpoint of death or first aortic event (elective aortic surgery or acute aortic syndrome) was compared between male and female by the Kaplan-Meier curves, log-rank test and subsequent Cox regression analysis.

Results

A total of 442 patients with MFS where included, 48.2% female and 56.2% index cases. Although systemic score and proband proportion was not different between both sexes, the diagnosis was earlier in males (p=0.01) (Table). Furthermore, among adult patients, males exhibited greater height, weight, and body surface area (BSA). Absolute aortic root diameter at baseline was greater in males, but not BSA-indexed diameters or z-scores.

Combined endpoint of death or aortic event was observed in 192 patients (120 male, 72 female, p=<0.00001). Female sex had better survival free of the combined endpoint in a multivariable Cox analysis (HR 0.41 95% CI=0.30–0.55) with a mean survival free of the combined endpoint of 41.3yrs in male and 61.4 years in females (p<0.0001) (Figure).Although a higher proportion of elective aortic interventions as first event was observed in males (66.7% vs 52.8%), the proportion of type A dissections was similar between both sexes (26.7 vs 26.4%) with increased frequency of type B dissections in females as first aortic event (4.2 vs 15.3%) (p=0.026)

Conclusions

Male patients with MFS present higher aortic root diameters but similar BSA-indexed and zscores than females. Survival free of first aortic event or death is reduced in male with MFS, with greater frequency of elective aortic intervention. Although this last is driven by absolute aortic diameter, no increase on type A dissection was observed in women. These findings might suggest a potentially less aggressive manifestation of proximal aortic disease in women with MFS.Table:Comparison male and female Marfan
Comparison of long-term prognosis between coronary artery disease and peripheral artery disease in haemodialysis and non-dialysis patients
Authors: Kumada Y , Kawai N , Ishida N , Nakamura Y , Takahashi H , Izawa H , Murohara T , Ishii H
Published: October 2024

Background

Patients on hemodialysis (HD) have been consistently recognized as a population with a high risk for cardiovascular diseases. However, it has not been clear which vascular disease had more impact on clinical prognosis. The aim of this study was to compare coronary artery disease (CAD) and peripheral artery disease (PAD) among HD and non-HD patients undergoing coronary artery bypass graft (CABG) and lower extremity bypass (LEB) surgery.

Methods

A total of consecutive 1,867 patients who initially and successfully underwent cardiovascular bypass surgery (242 CABG and 620 LEB in HD patients, 604 CABG and 401 LEB in non-HD patients) were enrolled in this study. They were followed up for up to 10-year. The primary endpoint was all-cause mortality.

Results

Cumulative mortality rates for 10-year were 15.6%, 21.8%, 38.7% and 58.9% after CABG in non-HD patients, LEB in non-HD patients, CABG in HD patients and LEB in HD patients, respectively (Figure). HD patients consistently had higher risk of mortality after cardiovascular bypass surgery compared to non-HD patients [adjusted hazard ratio (aHR) 3.04, 95% confidence interval (CI) 2.21-4.36, p<0.0001]. Similar results were observed after CABG and LEB in both, respectively (aHR 2.50, 95%CI 1.75-3.61, p<0.0001 for CABG and aHR 3.07, 95%CI 3.07, 95%CI 2.21-4.36, p<0.0001). Also, patients with LED tended to have higher risk of mortality compared to those with CABG (aHR 1.25, 95%CI 1.0.99-1.57, p=0.057) in entire cohort. However, the risk of mortality was significantly higher after LED than CABG in HD patients (aHR 1.34, 95%CI 1.02-1.81, p=0.042) but not in non-HD patients (aHR 1.00, 95%CI 0.67-1.49), p=0.98). In addition, HD patients with LEB had markedly higher risk of mortality compared to non-HD patients with CABG (aHR 3.50, 95%CI 2.62-4.74, p<0.0001).

Conclusion

Long-term prognosis was consistently poorer after cardiovascular surgery regardless of CABG or LEB in HD patients than in non-HD patients. The risk of mortality was also significantly higher after LEB than CABG in HD patients but not non-HD patients, and HD patients with LEB was considered to have the highest mortality risk in the study. Thus, PAD might be at more advanced atherosclerotic status than CAD in this high-risk population.
Remnant cholesterol, not LDL cholesterol, explains peripheral artery disease risk conferred by apolipoprotein B: a cohort study
Authors: Wadstrom B N , Pedersen K M , Wulff A B , Nordestgaard B G
Published: October 2024

Background

Elevated apolipoprotein B (apoB)-containing lipoproteins (=remnants + low-density lipoproteins [LDL]) are a major risk factor for atherosclerotic cardiovascular disease, including peripheral artery disease (PAD) and myocardial infarction. We tested the hypothesis that remnants and LDL both explain part of the increased risk of PAD conferred by elevated apoB-containing lipoproteins. For comparison, we also studied risk of chronic limb-threatening ischemia and myocardial infarction.

Methods

ApoB, remnant cholesterol, and LDL cholesterol were measured in 93,461 individuals without statin use at baseline from the Copenhagen General Population Study (2003-2015). During up to 15 years of follow-up, 1,207 had PAD, 552 had chronic limb threatening ischemia, and 2,022 had myocardial infarction in the national Danish Patient Registry. Remnant and LDL cholesterol were calculated from a standard-lipid profile. Remnant and LDL particle counts were additionally measured with nuclear magnetic resonance spectroscopy in 25,347 of the individuals. Results were replicated in 302,167 individuals without statin use from the UK Biobank (2004-2010).

Results

In the Copenhagen General Population Study, multivariable adjusted hazard ratios for risk of PAD per 1 mmol/L (39 mg/dL) increment in remnant and LDL cholesterol were 1.9 (95% confidence interval: 1.5-2.4) and 1.1 (1.0-1.2), respectively; corresponding results in the UK Biobank were 1.7 (1.4-2.1) and 0.9 (0.9-1.0), respectively. In the association from elevated apoB to increased risk of PAD, remnant and LDL cholesterol explained 73% (32-100%) and 8% (0-46%), respectively; corresponding results were 63% (30-100%) and 0% (0-33%) for risk of chronic limb-threatening ischemia, and 41% (27-55%) and 54% (38-70%) for risk of myocardial infarction; results for remnant and LDL particle counts corroborated these findings.

Conclusions

PAD risk conferred by elevated apoB-containing lipoproteins was explained mainly by elevated remnants, while myocardial infarction risk was explained by both elevated remnants and LDL.
Safety and efficacy of low-dose versus high-dose paclitaxel-coated balloons in patients with femoropopliteal lesions: an updated and meta-analysis
Authors: Desouki M A R , Mansour A M , Ali M A , Husain M A , Elnady M I , Mohamed A E , Abdelaziz A , Abdelazeem B , Suppah M , Mohamed A A , Lavie C , Slipczuk L
Published: October 2024

Introduction

Drug-coated balloons (DCBs) have reduced restenosis and reintervention of femoropopliteal lesions compared to uncoated percutaneous transluminal angioplasty (PTA). However, limited data are available on different dosages of the DCBs.

Purpose

We aimed to give a comprehensive analysis in this regard and update the current evidence.

Methods

We searched Scopus, Cochrane, PubMed, and WOS from inception till February 2024 to include all randomized controlled trials (RCTs) that addressed different dosages of DCBs in femoropopliteal lesions. The primary endpoint was all-cause death, primary patency, and amputation at six months, while the secondary outcomes were all-cause death, primary patency, and amputation at 12 months. Dichotomous data were pooled using Odds Ratio (OR) and 95% Confidence Interval (CI) in a random-effect model.

Results

A total of 21 studies, including 4081 patients in the analysis. Low-dose DCB was associated with high rates of primary patency compared to the standard dose at both 6 and 12 months of follow-up with the following values (OR: 2.46, 95% CI: 1.48 to 4.08, and 1.93, 95% CI: 1.5 to 2.49, receptively). Also, low-dose DCB reduced the incidence of clinically driven target lesion revascularization (CD-TLR) compared to the standard dose at 12 months (OR: 0.45, 95% CI: 0.31 to 0.65). Regarding high-dose DCB, higher primary patency rates were observed when compared to standard doses at 6 and 12 months (OR: 1.89, 95% CI: 1.19 to 2.99, and 5.47, 95% CI: 4.31 to 6.95, respectively). Moreover, high-dose DCB reduced the incidence of CD-TLR at 6 and 12 months of follow-up (OR: 0.33, 95% CI: 0.18 to 0.63, and 0.63, 95% CI: 0.48 to 0.84, respectively).

Conclusion

Low-dose DCBs were associated with higher primary patency without significant differences in all-cause mortality or amputation. On the other hand, high-dose DCBs were associated with a higher incidence of amputation without significant differences in other studied outcomes.Low dose Paclitaxel coated balloon vs CoHigh dose Paclitaxel coated balloon vs C