bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics in patients with adult-onset idiopathic peripheral pulmonary artery stenosis
Authors: Tamura Y , Tamura Y , Takemura R , Shigeta A , Hosokawa K , Taniguchi Y , Inami T , Adachi S , Tsujita I , Nakanishi N , Sato K , Sakamoto J , Tanabe N , Sugimura K 
Published: November 2023

Abstract

Background
Peripheral pulmonary artery stenosis (PPS) refers to the obstruction of the pulmonary artery from the pulmonary artery trunk to the peripheral arteries. Although pediatric PPS is well described, the clinical characteristics of adult-onset idiopathic PPS have not been established.

Purpose
To establish the disease profile of adult-onset PPS, we characterized the clinical background, laboratory and imaging findings, treatment, and prognosis.

Methods
The nationwide survey in Japan, supported by the government, retrospectively collected clinical data on patients with idiopathic PPS from multiple centers. This cohort comprised individuals aged 15 years and above who had pulmonary arterial stenosis confirmed through pulmonary angiography, indeed patients with chronic thromboembolic pulmonary hypertension or Takayasu arteritis were excluded. Patient backgrounds, imaging findings, treatment profiles, right heart catheterization findings, and long-term prognosis were collected. A comparison was made between the data obtained from prior-treatment and post-treatment right heart catheterization.

Results
Forty-five patients (median age at diagnosis: 38 years [Q1–Q3:28–56]; 29 males [64.4%]) with idiopathic PPS were enrolled from 21 centers. The median period between diagnosis of PPS and the final follow-up was 60 months [Q1–Q3: 24–114 months]. Eight patients (17.8%) were associated with moyamoya disease. Pulmonary angiography was performed in all patients for a definite diagnosis, and stenosis of segmental and peripheral pulmonary arteries was observed in 41 (91.1%) and 36 patients (80.0%), respectively. Thirty-six patients (80.0%) received treatment with pulmonary arterial hypertension (PAH)-specific drugs, 23 patients (51.1%) received combination therapy, and 25 patients (55.6%) received transcatheter pulmonary angioplasty. Right heart catheterization data showed improvements in both the mean pulmonary artery pressure (46 vs. 41 mmHg; p&lt;0.001) and pulmonary vascular resistance (738 vs. 506 dyn.s.cm-5; p&lt;0.001) from baseline to the final follow-up. The 3-, 5-, and 10-year survival rates of patients with idiopathic PPS were 97.6% (95% confidence interval [CI]:83.9–99.7), 89.7% [95% CI:69.9–96.6), and 68.6% (95% CI:43.9–84.2), respectively.

Conclusion
In this study, the patients with adult-onset idiopathic PPS presented with segmental and peripheral pulmonary artery stenosis. Although patients had severe pulmonary hypertension at baseline, they showed a favorable treatment response to the PAH-specific drugs combined with transcatheter pulmonary angioplasty.
Circulating biomarkers associated with aortic diameter in male and female thoracic aortic disease patients: a cross-sectional study
Authors: Meccanici F , Thijssen C G E , Dekker S , Bons L R , Gokalp A L , De Rijke Y B , Takkenberg J J M , Mokhles M M , Bekkers J A , Boersma E , Bouwens E , Van Den Bosch A E , Van Kimmenade R R J , Roos-Hesselink J W 
Published: November 2023

Abstract

Background
As thoracic aortic disease (TAD) is generally asymptomatic, biomarkers are needed to provide insight into early progression.

Purpose
We aimed to examine the association between circulating blood biomarkers and the maximal thoracic aortic diameter (TADmax).

Methods
In this cross-sectional study, consecutive adult patients with a thoracic aortic diameter ≥ 40 mm and/or genetically proven hereditary TAD (HTAD) visiting our specialized outpatient clinic between 2017-2020, were prospectively included. Venous blood sampling and computed tomography angiography and/or transthoracic echocardiography of the aorta were performed. Linear regression analyses were performed and estimates were presented as mean difference in TADmax in mm per doubling of standardized biomarker level.

Results
In total 158 patients were included (median age 61 [50.3-68.8] years, 37.3% female). HTAD diagnosis was confirmed in 36/158 (22.7%) patients. TADmax was 43.9 ± 5.2 mm in males versus 41.9 ± 5.1 in females, p=0.030. In unadjusted analysis, significant associations with TADmax were found for interleukin-6 (IL-6) (1.15 (95%CI 0.33-1.96), p=0.006), growth-differentiation factor-15 (GDF-15) (1.01 (95%CI 0.18-1.84), p=0.018), microfibrillar-associated protein 4 (MFAP4) (-0.88 (95%CI -1.71—0.05), p=0.039) and triiodothyronine (T3) (-2.00 (95%CI -3.01—0.99), p&lt;0.001). The association fherer MFAP4 was stronger in females (p=0.020) and for homocysteine an inverse association was observed when compared to males (p=0.008). When adjusted for age, sex, hyperlipidaemia and HTAD, total cholesterol (1.10 (95%CI 0.27-1.93), p=0.010) and T3 (-1.20 (95%CI -2.14—0.25), p=0.014) were significantly associated with TADmax.

Conclusions
Circulating biomarkers indicative of inflammation, lipid metabolism and thyroid function, might be associated with thoracic aortic disease severity. Possible distinct biomarker patterns for males and females warrant further investigation.Figure 1Table 1
Worse glycemic control is associated with an impaired arterial energy transfer pattern in elderly with diabetes
Authors: Tas A , Broyd C J , Kara I , Umman S , Sezer M 
Published: November 2023

Abstract

Background
Worse glycaemic control is known to exacerbate endothelial insult, increasing macro- and microvascular complication risks in diabetes. Impaired intracranial haemodynamics have been frequently reported in patients with diabetes alongside with malperfusion causing structural abnormalities, and poor cognitive and cortical functionality (1-2).Assessment of the alterations in energy transfer characteristics derived from hemodynamic signals may provide novel mechanistic information about how worse glycaemic control may affect cerebrovascular perfusion. Wave reflection index(WRI) is a previously proposed measure of arterial energy transfer efficiency which reflects distal impedance mismatch(3-4).

Purpose
We aim to interrogate potential relationship between a worse glycaemic control and a less efficient arterial energy transfer, which could enhance our understanding of the cerebrovascular-cortical functional coupling on a mechanistic basis in elderly with diabetes.

Methods
Left middle cerebral artery wave intensity (WI) was computed with arterial blood pressure and flow velocity (transcranial Doppler) signal as previously described (WI = (dP/dt)*(dU/dt)) (Figure 1). Standard statistical tests were used to interrogate the relationship between glycated haemoglobin levels (HbA1c) and WI parameters.

Results
In 36 patients with diabetes mellitus type-2 (DM2) (mean age = 65.7 ± 8.8 years), backward compression wave intensity (BCWI) and wave reflection ratio (WRI= BCWI/FCWI) were significantly correlated with HbA1c levels before (rBCWI: 0.409 pBCWI:0.013; rWRI:0.345 pWRI:0.040) and after (rBCWI: 0.410 pBCWI:0.018, rWRI:0.351 pWRI:0.045) adjusting for age, sex and mean arterial pressure (Figure 2).

Conclusion(s)
In elderly patient with DM2, higher HbA1c values indicating worse glycaemic control are significantly correlated with altered cerebrovascular energy transfer characteristics as assessed by MCA wave intensity analysis. Continuous relationship between worse glycaemic control and higher wave reflection index (a measure of less efficient energy transfer in arterial system and distal impedance mismatch) may imply that the use of energy transfer related indices alongside with conventional hemodynamic indices may help providing a more comprehensive pathophysiological understanding about how cardiovascular risk factors interfere with perfusion.Computation of Wave IntensityMain Results
Comorbidity burden assessed by the charlson comorbidity index and its influence on prognosis of patients with pulmonary embolism
Authors: Keller K , Schmitt V , Espinola-Klein C , Munzel T , Konstantinides S , Hobohm L 
Published: November 2023

Abstract

Background
Pulmonary embolism (PE) is an acute cardiovascular syndrome and can be associated with high morbidity and mortality. Short-term outcomes of PE are closely related to right ventricular dysfunction (RVD) and the patient’s haemodynamic status as well as age and comorbidity profile. According to the current ESC guidelines for management of acute PE patients, initial risk stratification is based on clinical symptoms and signs, whereby haemodynamic instability indicates a high-risk status with substantial increase of the risk for early death. However, the vast majority of PE patients are haemodynamically stable at presentation; they require further risk stratification with clinical, imaging, and laboratory indicators of PE severity as well as the patient’s comorbidity profile and other aggravating conditions. The pulmonary embolism severity index (PESI) and the simplified pulmonary embolism severity index (sPESI) are implemented for risk stratification in the ESC guidelines. However, other tools may be more suitable for characterizing the comorbidity profile of PE patients. One established approach to evaluate the comorbidity profile is the Charlson Comorbidity Index.

Purpose
The objective of the present study is to investigate the impact of the comorbid profile on prognosis of patients with acute PE in a large nationwide inpatient sample.

Methods
We used the German nationwide inpatient sample to analyse the Charlson Comorbidity Index score of all hospitalised patients with PE in Germany 2005-2020 (source: RDC of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2005-2020, own calculations). The patients were categorized in the very-low severity (Charlson Comorbidity Index 0 points, mild severity (Charlson Comorbidity Index 1-2 points), moderate severity (Charlson Comorbidity Index 3-4 points) and severe severity (Charlson Comorbidity Index &gt;4 points) and severity classes were compared.

Results
Overall, 1,373,145 hospitalizations of patients with acute PE (53.0% females, 55.9% aged ≥70years) were recorded in Germany between 2005 and 2020; they were stratified by the Charlson Comorbidity Index class. Among these, 100,156 (7.3%) were categorized as very-low, 221,545; (16.1%) as mild, 394,965 (28.8%) as moderate, and 656,479 (47.8%) as patients with a severe comorbidity burden. In-hospital case-fatality increased with the current Charlson Comorbidity Index class: 3.6% in very-low, 6.5% in mild, 12.1% in moderate and 22.1% in the severe Charlson Comorbidity Index class (P&lt;0.001). The Charlson Comorbidity Index class was associated with increased in-hospital case-fatality (OR 2.014 [95%CI 2.000-2.027], P&lt;0.001).

Conclusion
The results of our study may help to better understand and measure the association between an aggravated comorbidity profile and increased in-hospital case-fatality in patients with acute PE.
Dual pathway inhibitor therapy switched from dual antiplatelet therapy reduces risk of recurrent in-stent occlusion after endovascular therapy for femoropopliteal in-stent occlusion
Authors: Nakao S , Iida O , Asai M , Masuda M , Okamoto S , Ishihara T , Nanto K , Tsujimura T , Matsuda Y , Hata Y , Uematsu H , Toyoshima T , Higashino N , Kusuda M , Mano T 
Published: November 2023

Abstract

Background
Femoropopliteal (FP) in-stent occlusion (ISO), which increases the risk of repetition of reintervention and worsens the limb prognosis, is substantially encountered in clinical setting.1,2 Although previous study demonstrated that dual pathway inhibitor therapy (DPIT) reduced major adverse cardiovascular and limb events, whether this would be effective as anti-thrombotic therapy after endovascular therapy (EVT) for FP-ISO.3

Purpose
To investigate whether DPIT reduces a risk of recurrent ISO after EVT for FP-ISO.

Methods
We retrospectively studied 117 limbs (chronic limb-threatening ischemia: 52%, chronic total occlusion: 74%) in 110 symptomatic patients with lower extremity arterial disease (male: 55%, diabetes mellitus: 49%) due to FP-ISO between August 2012 and October 2021. We compared the clinical outcomes of patients who were switched from dual antiplatelet therapy (DAPT) to DPIT with those who continued DAPT (DPIT group: 25 limbs in 25 patients, DAPT group: 92 limbs in 85 patients) after FP-ISO revascularization. The outcome measures were recurrent ISO and bleeding complications defined as the bleeding academic research criteria (BARC) and the International Society on Thrombosis and Haemostasis (ISTH). Cox proportional hazards regression models were used to identify prognostic factor of recurrent ISO.

Results
The 1-year cumulative incidence of recurrent ISO was significantly lower in DPIT group. (24.0±9.4% vs. 54.1±5.8%, p=0.037, Figure 1). The 1-year cumulative incidence of bleeding complications were similar between two groups (BRAC 3 or 5 bleeding: 4.2% vs. 2.4%, p=0.63), ISTH major bleeding: 12.6% vs. 11.4%, p=0.86) (Figure 2). Multivariate analysis revealed that DPIT group (hazard ratio [HR]: 0.34, 95% confidential interval [CI] 0.13-0.86, P=0.004) significantly associated with a reduced risk of recurrent ISO, whereas higher age (HR: 1.05, 95%CI 1.01-1.09, P=0.006) and poor BTK run-off (HR: 4.77, 95%CI 1.76-12.91, P=0.002) were significantly associated with an increased risk.

Conclusion
Switching from DAPT to DPIT after EVT for FP-ISO reduced the risk of recurrent ISO without increasing the risk of bleeding, while higher age and poor BTK run-off increased the risk of recurrent ISO.Figure 1Figure 2
Trimethyllysine, trimethylamine N-oxide, and long-term risk of stroke: the western norway coronary angiography cohort
Authors: Bjornestad E O , Nygaard O , Svingen G F T , Pedersen E R , Sulo G , Ueland P M , Orn S , Svenningsson M M , Laaksonen R , Dhar I 
Published: November 2023

Abstract

Background
Trimethyllysine (TML) is a precursor of the gut-microbiota derived metabolite trimethylamine N-oxide (TMAO), and both biomarkers are associated with adverse cardiovascular outcomes. Whether circulating levels of TML or TMAO predict long-term risk of stroke is uncertain.

Purpose
To examine prospective associations of plasma TML and TMAO with long-term risk of total and ischemic stroke.

Methods
By Cox regression analyses, risk-associations were examined among 4132 patients undergoing elective coronary angiography for suspected stable coronary heart disease. Endpoints were obtained from the Cardiovascular Disease in Norway project.

Results
Median levels of TML and TMAO were 0.67 and 5.7 µmol/L, respectively. Median age was 62 years and 28.1% of the participants were female. During a median follow up of 7.4 years, 240 (5.8%) patients experienced a stroke, of which 193 were ischemic strokes. After multivariable adjustments for cardiovascular risk factors, the hazard ratios (95% confidence intervals) per 1 standard deviation increase in log-transformed plasma TML were 1.05 (0.92-1.19, p=0.49) for total stroke and 0.99 (0.86-1.15, p=0.92) for ischemic stroke. Corresponding risk estimates were 0.99 (0.86-1.13, p=0.83) and 0.95 (0.82-1.12, p=0.55) per 1 standard deviation increase in log-transformed plasma TMAO.

Conclusion
In this large prospective cohort of patients with suspected coronary heart disease, neither plasma TML nor plasma TMAO predicted long-term (∼7 years) risk of stroke.
A cluster of blood-based protein biomarkers associated with decreased cerebral blood flow relates to future cardiovascular events in patients with cardiovascular disease
Authors: Overmars M , Kuipers S , Van Es B , De Bresser J H J M , Hoefer I E , Bron E , Van Solinge W W , Kappelle L J , Van Osch M J P , Teunissen C , Biessels G J , Haitjema S 
Published: November 2023

Abstract

Introduction
Biological processes underlying decreased cerebral blood flow (CBF) in patients with cardiovascular disease (CVD) are largely unknown. We hypothesized that identification of protein clusters associated with lower CBF in patients with CVD may explain underlying processes.

Methods
In 428 participants (74% cardiovascular diseases; 26% reference participants) from the Heart-Brain Connection Study, CBF was measured with MRI in normal-appearing grey matter with pseudo-continuous arterial spin labeling. We assessed the relation between 92 plasma proteins from the Olink® cardiovascular III panel and CBF using cluster-based analyses and generated a Biomarker Compound Score (BCS). The BCS was related to cardiovascular risk and observed cardiovascular events within 2-year follow-up.

Results
Thirteen proteins were associated with CBF (ρSpearman range: -0.10 to -0.19, pFDR-corrected &lt;0.05), and formed one cluster. The cluster primarily reflected extracellular matrix organization processes. The BCS was higher in patients with CVD compared to reference participants (pFDR-corrected &lt;0.05) and was associated with cardiovascular risk (p &lt;0.001) and cardiovascular events (OR 2.05, p &lt;0.01).

Conclusions
We identified a cluster of plasma biomarkers related to CBF, which is related to future cardiovascular events in patients with CVD. The cluster primarily reflected extracellular matrix organization processes, which represent potential targets to preserve CBF in patients with CVD.
Discordance between quantitative coronary angiography and fractional flow reserve or intravascular ultrasound: a substudy of the FLAVOUR trial
Authors: Lee J H , Jeon H S , Lee J W , Youn Y J , Ahn S G , Kang J H , Koo B K 
Published: November 2023

Abstract

Background
Discrepancies between quantitative coronary angiography (QCA) and fractional flow reserve (FFR) or intravascular ultrasound (IVUS) are often observed in coronary lesions with intermediate stenosis.

Objectives
We investigated the impact of physiology- or intracoronary imaging-directed revascularization strategies on clinical outcomes in patients with discordant coronary lesions between QCA and FFR or IVUS.

Methods
This study was a post hoc analysis of the FLAVOUR study, an investigator-initiated, prospective, randomized, open-label, multinational trial performed at 18 sites in Korea and China. In the FLAVOUR study, 200 patients with ≥60% diameter stenosis (DS) deferred percutaneous coronary intervention (PCI) according to FFR &gt; 0.8 (n=141) or a minimal lumen area &gt; 3 mm2 or 3-4 mm2 with a plaque burden &lt;70% on IVUS whereas 351 patients with &lt;60% DS performed PCI according to positive FFR (n=118) or positive IVUS (n=233) results. The primary outcome was a patient-oriented composite outcome (POCO), a composite of death, myocardial infarction, or revascularization.

Results
The incidence of discordance was 28.1% in the FFR group and 32.4% in the IVUS group. At 24 months, among patients with ≥60% DS, the incidence of POCO was similar between FFR-guided and IVUS-guided deferral strategies (4.4% vs. 3.4%, p=0.757). Among patients with &lt;60% DS, FFR-directed or IVUS-directed PCI did not differ in the POCO incidence (5.2% vs. 2.6%, p=0.207). However, FFR-guided PCI showed a higher incidence of periprocedural myocardial infarction than IVUS-guided PCI in &lt;60% DS lesions (2.6% vs. 0.0%, p=0.014).

Conclusions
In patients with discordant intermediate stenosis between QCA and FFR or IVUS, physiology- and imaging-directed revascularization strategies are comparable concerning POCO at 24 months.
Predictors of optical coherence tomography-defined calcified nodules in patients with acute coronary syndrome: a substudy from TACTICS registry
Authors: Sugiyama T , Kakuta T , Hada M , Hoshino M , Yonetsu T , Kimura S , Mizukami T , Yamamoto M H , Kondo S , Wakabayashi K , Suwa S , Kobayashi N , Higuma T , Mori H , Shinke T 
Published: November 2023

Abstract

Background
We investigated the clinical predictors of optical coherence tomography (OCT)-defined calcified nodules (CN) in patients with acute coronary syndrome in a prospective multicenter registry.

Methods
We investigated 695 patients enrolled in TACTICS registry who underwent OCT assessment of the culprit lesion during primary percutaneous coronary intervention. OCT-CN was defined as eruptive calcific nodules into the lumen with disruption of the fibrous cap and an underlying calcified plate. Patient characteristics were compared between patients with and without OCT-CN.

Results
OCT-CN was detected in 28 patients (4.0%). Patients with OCT-CN were older (75.0 ± 11.3 vs. 65.7 ± 12.7 years, p &lt; 0.001) and had a higher prevalence of diabetes mellitus (50.0% vs. 29.4%, p = 0.034), hemodialysis (21.4% vs. 1.6%, p &lt; 0.001) and heart failure (Killip 3/4, 21.4% vs. 5.7%, p = 0.003) than patients without OCT-CN. The angiographic SYNTAX score was higher in patients with OCT-CN than those without (median, 15 [interquartile range, 11, 25] vs. 11 [7, 19], p = 0.003). Multivariable analysis demonstrated that age (odds ratio [OR], 1.072; 95% confidence interval [CI], 1.033–1.116; p &lt; 0.001), Killip class 3/4 (OR, 4.466; 95% CI, 1.472–11.943; p = 0.004) and hemodialysis (OR, 16.571; 95% CI, 4.946–52.863; p &lt; 0.001) were significantly associated with the presence of OCT-CN. In non-dialysis patients (n=678), age (OR, 1.081; 95% CI, 1.035–1.135; p &lt; 0.001), Killip class 3/4 (OR, 4.414; 95% CI, 1.327–12.709; p = 0.009) and diabetes mellitus (OR, 3.046; 95% CI, 1.251–7.594; p = 0.014) were significantly associated with the presence of OCT-CN.

Conclusions
TACTICS registry demonstrated the clinical predictors of OCT-CN, which may be associated with worse prognosis.
The effect of ventricular microvascular dysfunction on cardiomyocyte excitation-contraction coupling and mitochondria
Authors: Boegner M , Huettemeister J , Weiss J , Schallopp L , Falk V , Schoenrath F , Just I A , Stawowy P , Hohendanner F 
Published: November 2023

Abstract

Introduction
Microvascular dysfunction is a hallmark feature of cardiac allograft vasculopathy in HTx patients and associated with heart failure and coronary artery disease. On a cellular level, impaired mitochondrial respiration has been associated with the disease, however the exact mechanisms remain elusive.

Objective
The aim of this study was to determine the effect of microvascular dysfunction on functional and structural properties of cardiomyocytes isolated from ventricular biopsies of HTx patients.

Methods
We functionally assessed coronary artery microvasculature using guidewire based coronary flow reserve(CFR)/microvasculatory resistance (IMR) measurements (Abbott) in 13 post-HTx patients with angiographically normal coronary arteries or normal FFR. Ventricular (RV septum) myocardial biopsies were obtained for in-vitro measurements and single ventricular cardiomyocytes were isolated using enzymatic digestion. Cells were electrically stimulated (1 Hz) and subcellular Ca2+ signalling during excitation-contraction coupling was measured using confocal imaging (Fluo-4 AM). In a subset of cardiomyocytes mitochondrial density was quantified upon staining with Mitotracker Red FM (otsu thresholding).

Results
Microvascular dysfunction (MVD) measured by IMR was present in 6 of 13 patients with a mean IMR of 56±11 and 13±3 in MVD and CTRL, respectively. CFR did not differ between MVD and CTRL. Ca2+ transients during excitation-contraction coupling in isolated ventricular cardiomyocytes from a subset of patients showed unaltered amplitudes (1.2±0.01 vs. 1.3±0.05; a.u. F/F0). In addition, Ca2+ release (i.e. time to peak Ca2+) and Ca2+ removal (i.e. tau) were not significantly different between MVD and CTRL. However, mitochondrial density was significantly increased in MVD vs. CTRL, indicating subcellular changes associated with MVD.

Conclusion
In-vivo ventricular microvascular dysfunction is associated with preserved excitation-contraction coupling in-vitro, potentially owing to compensatory changes on the mitochondrial level.