bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of pulmonary embolism among patients presenting to emergency department for hemoptysis
Authors: Vanni S , Gori L , Coppa A , Nazerian P , Giannasi G , Ruggiano G , De Curtis E , Baldini A , Pepe G , Magazzini S
Published: October 2022

Background

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

Objectives

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

Methods

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

Results

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

Conclusions

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

Funding Acknowledgement

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

Background

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

Methods

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

Results

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

Conclusions

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

Funding Acknowledgement

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

Background

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

Purpose

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

Methods

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

Results

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

Conclusion

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

Funding Acknowledgement

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

Introduction

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

Purpose

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

Methods

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

Results

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

Conclusions

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

Funding Acknowledgement

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

Background

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

Purpose

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

Methods

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

Results

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

Conclusion

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

Funding Acknowledgement

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

Introduction

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

Purpose

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

Methods

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

Results

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

Conclusion

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

Funding Acknowledgement

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

Background

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

Purpose

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

Methods

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

Results

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

Conclusion

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

Funding Acknowledgement

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

Background

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

Methods

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

Results

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

Conclusion

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

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Swedish state under the agreement concerning research and education of doctors [grant number ALFGBG-427301]; the Swedish Society for Physicians, the Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, Sweden, and the Swedish Heart and Lung Foundation [grant number 2015-0438]; the Swedish Research Council [grant numbers 2013-5187 (SIMSAM), 2013-4236]; and the Swedish Council for Health, Working Life and Welfare (FORTE) [grant numbers 2013-0325]
Celiprolol to prevent arterial events in patients with vascular Ehlers-Danlos and neither symptomatic nor silent arterial event. A retrospective cohort study from the French national reference center
Authors: Mazzella J M , Oehmichen B , Billon C , Nicolas S , Lahlou-Laforet K , Frank M , Jeunemaitre X , Mirault T
Published: October 2022

Background

Vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder, leading to mainly arterial complications, caused by COL3A1 pathogenic variations. Ong et al. (Lancet 2010) showed that the introduction of celiprolol significantly reduced arterial events in a predominantly symptomatic population on arterial level. We reported the benefit of full dose of Celiprolol in longitudinal study to prevent arterial events in Frank et al. (JACC 2019). To our knowledge, there is no data regarding the benefit of celiprolol in patients without any arterial event.

Purpose

The aim of this study was to assess the occurrence of arterial events during follow-up in vEDS patients without arterial event.

Methods

All patients – probands and relatives – with a pathogenic variation in COL3A1 diagnosed at the Referral Centre for Rare Vascular Diseases since 2001 and at least one arterial tree assessment were included. We then focused on vEDS patients without any arterial event. We retrospectively analyzed the duration of follow-up, the occurrence of arterial events during follow-up, and the introduction and dose of celiprolol, especially at the time of occurrence of an arterial event.

Results

Among the 230 patients included, 144 (63%) had at least one symptomatic arterial event, 44 (19%) had only silent arterial event and 67 (29%) had no arterial event at the first arterial tree assessment event. Patients with no arterial event were significantly younger at this visit compared with the two other groups with a median age of 23 vs. 38 and 39 years (silent and symptomatic) (p<0.05). Patients with no arterial event were more frequently relatives (73%) than probands (27%) (p<10–3). Celiprolol was introduced in 48 (72%) of the 67 patients with no arterial event after positive genetic diagnosis disclosure or during one of the outpatient visit. During follow-up, 22 patients had a first arterial event at a median age of 29 years: 16 (33%) were receiving celiprolol and 6 (32%) were not. But the median follow-up duration was 4 years for the 48 treated patients vs. 2 years for the 19 untreated patients (p=0.03).

Conclusions

Genetic testing of the relatives of probands with vEDS remains of utmost importance as one quarter presented with symptomatic arterial event and one fifth had silent arterial event at initial arterial tree assessment. For patients with no arterial event, those without celiprolol have a similar incidence of arterial events than those with celiprolol, however their follow-up duration was twice shorter suggesting a higher incidence rate or arterial event in the absence of celiprolol.

Funding Acknowledgement

Type of funding sources: None.
Course of ankle-brachial-index 12 months after intravascular lithotripsy in calcified peripheral lesions
Authors: Aftanski P , Thieme M , Schulze P C , Klein F , Moebius-Winkler S , Kretzschmar D
Published: October 2022

Background

Intravascular lithotripsy (IVL) is a relatively novel treatment option for calcified lesions in peripheral artery disease. Little is known about the mid to long-term functional status of the patients and target lesion revascularization rate (TLR) after IVL only procedure.

Purpose

To evaluate the course of ankle-brachial-index (ABI) and to assess the rate of revascularization 1 year after intravascular lithotripsy performed on calcified peripheral lesions.

Methods

Between December 2018 and January 2021 IVL was performed on 61 limbs of 51 patients presenting with Rutherford classes 2–5. Ankle-brachial-index (ABI) was documented before the procedure as well as 1 day, 6 months and 1 year after the procedure within a single center real-life registry. Further endpoint was revascularization with PTA or peripheral bypass surgery. The vast majority of cases were done as IVL only procedure (58%) All procedures were done in upper leg/pelvic stenosis.

Results

ABI measurement after 12 months was done in 42 of 51 patients (82%). Three pts were missed due to media sclerosis. Due to loss of follow-up, ABI after 6 months could not be performed on 4/61 patients (7,8%) and 12-month-ABI in another 8/51 cases (15,6%). Initial baseline ABI of 0.6±0.26 before the procedure increased to 0.8±0.25 (p<0.0001) one day afterward. After 6 months, the ABI of 0.8±0.27 (n=49; p<0.0001) was still significantly improved compared to baseline. After 1 year, ABI with 0.7±0.22 was still improved, however not significantly different from baseline (Figure 1). Target lesion revascularization was needed in 7 patients (13%), 4 with subsequent IVL, 3 with PTA and 2 with peripheral bypass surgery.

Conclusions

In our large single center registry, IVL performed mainly as a stand-alone procedure was safe and effective even after a mid-term follow up. TLR was necessary in 13%, which is lower than in previous published IVL data (20,7% as in DISRUPT-PAD-II) [1]. ABI after 12 months improved but did maintain statistical significance, compared with other procedure like scoring balloon [2].

Funding Acknowledgement

Type of funding sources: None.
The additive predictive value of arterial stiffness for outcome to endothelial glycocalyx and SCORE in middle age individuals: 6 years follow-up
Authors: Ikonomidis I , Thymis J , Koliou G A , Simitsis P , Katsanos S , Pavlidis G , Kousathana F , Kostelli G , Katogiannis K , Kountouri A , Triantafyllidi H , Parissis J , Lekakis J , Filippatos G
Published: October 2022

Background/Aim

Arterial stiffness is involved in the clinical course of atherogenesis. We have previously shown that PBR, a marker of glycocalyx integrity is predictor of cardiovascular events in patients without established cardiovascular disease. The purpose of this study was to investigate whether altered arterial properties of the vessels confers predictively and additively to estimation of cardiovascular risk.

Methods

Pulse wave velocity carotid-femoral (PWVc-f), the gold standard method to assess arterial stiffness, was measured non-invasively by Complior device. Increased PWV(c-f), especially above 10 m/s, indicates increased arterial stiffness. We measured baseline PWV(c-f) in 600 apparently healthy subjects (47.61±13.84 years old, 50.1% males), without established cardiovascular disease. We prospectively monitored the occurrence of major cardiovascular events (MACE-death, myocardial infarction, stroke and heart failure hospitalization) during a 6-year follow-up period using electronic records and clinic visits.

Results

Fifty-seven MACEs were documented during follow-up. In univariate analysis, subjects with increased PWV were found to exert greater risk for MACEs (hazard ratio (HR): 1.09, 95% CI: 1.02–1.17, p=0.01). In all subjects, PWV predicted higher risk for MACEs in a model including PBR, sex, age, hyperlipidemia, diabetes, hypertension, current smoking, family history of coronary artery disease and treatment with ACEi/ARBs or lipid lowering agents (HR: 1.12; 95% CI: 1.04–1.17, p=0.029,net reclassification improvement (NRI): 23%; C-statistic: from 0.644 to 0.697). However, only in participants older than 50 years old, PWV was an independent and additive predictor of outcome when added in a model including PBR, SCORE, those risk factors not included in SCORE (diabetes, family history of CAD) and medication (HR: 1.09; 95% CI: 1.02–1.13, NRI: 23.8%, C-statistic increase from 0.703 to 0.762, p<0.01).

Conclusion

Arterial stiffness is an independent and additive predictor to endothelial glycocalyx and SCORE for adverse outcome at 6 years follow-up in individuals over 50 years old.

Funding Acknowledgement

Type of funding sources: None.
Rehospitalizations, repeated aortic surgery, and death in initial survivors of surgery for Stanford type A aortic dissection and the significance of age – a nationwide registry-based cohort study
Authors: Gundlund A , Koeber L , Hoefsten D E , Vester-Andersen M , Pedersen M W , Torp-Pedersen C , Kragholm K , Soegaard P , Fosboel E L
Published: October 2022

Background

All patients with type A aortic dissections, regardless of age, are recommended urgent aortic surgery. However, studies exploring long term outcomes in survivors are sparse, and especially, the significance of age on long-term outcomes remain unclear.

Purpose

We described and compared incidences across age groups of post-discharge readmission, repeated aortic surgery, and death in patients who survived surgery and hospitalization for type A aortic dissection.

Methods

Using data from Danish nationwide registries, we identified patients hospitalized with Stanford type A aortic dissections from 2006–2018. Survivors of hospitalization and surgery on the ascending aorta and/or aortic arch comprised the study population (Figure 1). Using cumulative incidence plots taking death into account as a competing risk and Cox regression analysis, we described long-term outcomes (rehospitalizations, repeated aortic surgery, and death) and compared different age groups. The diagnosis of type A aortic dissection in the registries used, was validated from 191 clinical records to have a positive predictive value of 94.8%.

Results

Of 606 initial survivors of surgery and hospitalization with type A aortic dissection, 236 (38.9%) were <60 years old (group I), 194 (32.0%) were 60–69 years old (group II), and 176 (29.1%) were >69 years old (group III). Figure 2 shows cumulative incidences of outcomes according to age. During the first year, 62.5% were re-hospitalized (median number of days hospitalized was 2 days (IQR 1–8 days) and 1.4% underwent repeated aortic surgery with no significant differences across age groups (P=0.68 and P=0.39, respectively). Further, 5.9% died (group I: 3.0%, group II: 8.3%, group III: 7.4%, P=0.04). After 10 years of follow up, 8.0% had undergone repeated aortic surgery (group I: 11.5%, group II: 8.5%, group III: 1.6%, P=0.04) and 10.2% (group I), 17.0% (group II), and 22.2% (group III) had died (P=0.01). In adjusted analyses, no age differences were found in one-year outcomes, while age >69 years (group III) compared with age <60 years (group I) was associated with a lower rate of repeated aortic surgery (hazard ratio 0.17, 95% confidence interval 0.04–0.78) and a higher rate of all-cause mortality (hazard ratio 2.44, 95% confidence interval 1.37–4.34) in the 10-years analysis.

Conclusion

Among survivors of type A aortic dissections, rehospitalizations the first year after discharge were common among all age groups, but survival was high. Repeated aortic surgery was rare, and significantly more common among younger than older patients. Evaluations of quality of life in survivors of type A aortic dissections are needed.

Funding Acknowledgement

Type of funding sources: None.
Impact of poor below-the-knee run-off on stent failure of femoro-popliteal arteries in healthy swine model
Authors: Nakamura N , Torii S , Aihara K , Kato T , Ikari Y , Nakazawa G
Published: October 2022

Background

Poor below-the-knee (BTK) run-off is reported to be one of the predictors of stent failure after endovascular treatment to femoro-popliteal arteries (1), however, the mechanism of stent failure has never been characterized before. The aim of the current study was to evaluate impact of poor BTK run-off on stent failure in healthy swine femoro-popliteal (FP) lesions, and to compare the outcome of a bare-metal stent (BMS) and two drug-eluting stents (DES) in the arteries with poor BTK run-off.

Method

Fluoropolymer-coated paclitaxel-eluting stents (FP-PES, Eluvia) and BMS were implanted in bilateral femoral arteries of 6 healthy swine following coil embolization in both tibial arteries to induce poor BTK run-off. FP-PES and polymer-free paclitaxel-coated stents (PF-PCS, Zilver-PTX) were also implanted in 6 swine with the same fashion. Angiography with an optical coherence tomography (OCT) at one month followed by histological analysis was performed for each lesion.

Result

Angiography demonstrated that in-stent restenosis was observed exclusively in BMS, and percent stenosis was significantly less in FP-PES compared with BMS (FP-PES vs. BMS, median [interquartile range (IQR)], 17.8% [16.6–28.7] vs. 79.3% [64.2–87.2], respectively, p=0.03). FP-PES also demonstrated significantly less percent stenosis compared with PF-PCS (FP-PES vs. PF-PCS, 8.9% [4.7–44.7] vs. 31.2% [23.3–51.2], respectively, p=0.03). Histopathological evaluation demonstrated that organizing and/or organized fibrin thrombus was the main feature of the restenotic lesions, suggesting a risk of thrombus attachment in the FP lesions with poor BTK run-off. Biologic drug effect such as medial smooth muscle cell (SMC) loss score was significantly greater in FP-PES compared with BMS (4.0 [3.3–4.0] vs. 2.0 [1.0–3.0], respectively, p<0.01), whereas, similar between FP-PES and PF-PCS (4.0 [3.0–4.0] vs. 4.0 [3.0–4.0], respectively, p=0.88).

Conclusion

Thrombus attachment would be the main causes of restenosis in FP lesions with poor BTK runoff. The results of the current study suggest that not only paclitaxel drug effect, but also anti-thrombotic effect of fluoropolymer might be needed to prevent stent failure.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): This study is supported by Boston Scientific.
Income-based differences in outpatient care of peripheral artery diseases in Germany
Authors: Messiha D , Petrikhovich O , Lortz J , Mahabadi A A , Hering R , Schulz M , Rassaf T , Rammos C
Published: October 2022

Background

Peripheral artery disease (PAD) is a major manifestation of atherosclerosis and a risk factor for morbidity and mortality. Guideline-recommended therapy and specialized outpatient care are essential for optimal treatment. Income-based inequalities in diagnosis and treatment of cardiovascular diseases are present, while differences for PAD are scarse. Knowledge of the treatment structures in the outpatient setting are essential to identify and solve income-based inequalities in this high-risk population.

Purpose

Aim of the study was to identify income-based inequalities in outpatient treatment care and pharmacotherapy in PAD patients.

Methods

We analyzed income-based differences in PAD prevalence, pharmacotherapy (statins, antiplatelets) and treatment by specialized outpatient care (angiology, vascular surgery, cardiology) in all statutorily insured patients with PAD presenting to outpatient care facilities in Germany between 2009 and 2018. The study is based on ambulatory claims data of the panel doctors' services according to §295 SGB V and drug prescription data according to §300 SGB V. Diagnosis of PAD was defined upon medical diagnoses of PAD ICD I70.2-9. Statistical analysis was performed with chi-squared test for trend and two-way Anova.

Results

Overall, 17,633,970 patients were included in the study. Prevalence of PAD was higher in low-income states. This income-driven gap widened between 2009 (2.3% vs 1.7%) and 2018 (4.4% vs 2.8%). Angiology outpatient care density was higher in low-income states, whereas vascular surgery and cardiology outpatient care density was higher in high-income states (p<0.05). While overall specialised outpatient care was underutilized, patients in low-income states were more likely to present to angiologists, while patients in high-income states more frequently presented to vascular surgeons. Patients with more progressed PAD stages were less likely to present to a specialist and to receive guideline recommended medical therapy, irrespective of the income-structure.

Pharmacotherapy also showed income-based differences. While overall prescription rates of statins and antiplatelet drugs were low, patients in low-income states had higher prescription rates than patients in high-income states. The income-driven gap decreased between 2009 and 2016 (statins: 2009 60% vs 48%; 2016 68% vs 65%; antiplatelets: 2009 50% vs 39%; 2016 53% vs 51%).

Conclusion

Our results demonstrate that income-based differences in pharmacotherapy and specialized outpatient care of PAD patients are evident in Germany. While overall outpatient treatment by vascular specialists and guideline recommended medical therapy with antiplatelets and statins are low, German low-income states have higher PAD prevalence, a higher angiology than vascular surgery density and higher prescription rates of guideline recommended pharmacotherapy.

Funding Acknowledgement

Type of funding sources: None.
Evaluation of symptomatic peripheral artery disease with media sclerosis using shear wave elastography of the lower limb muscle
Authors: Maslarska M , Piepenburg S , Kaier K , Freund G , Bode C , Hehrlein C
Published: October 2022

Background

Symptomatic peripheral artery disease (PAD) is challenging to diagnose in the presence of media sclerosis with incompressible arteries since standard ankle-brachial index (ABI) cannot be applied. Shear wave elastography (SWE) provides a novel ultrasound technique to measure muscle stiffness and to visualize muscle deficits at rest and during contraction. Furthermore, reduced muscle stiffness correlates with a possible hypoperfusion in the affected area. It is fast, non-invasive and associated with peripheral muscle weakness in chronic heart failure patients.

Purpose

SWE presents an important diagnostic tool for patients with PAD and concomitant media sclerosis. In this prospective observation study we evaluated the alterations of muscle stiffness (measured in kPa) at rest and during controlled activity.

Methods

Fifteen patients with peripheral artery disease and media sclerosis were included in this pilot study. Thirteen patients were symptomatic in different stages of PAD as a result of significant arterial stenosis/occlusions of the lower legs as assessed by oscillography and duplex sonography. ABI was invalid due to media sclerosis in all 15 patients. The examination was performed at rest and during contraction depicted by active dorsal flexion of the foot on both sides. The medial gastrocnemius muscle was used as a region of interest.

Results

Mean SWE measurements of medial gastrocnemius muscles showed significant muscle weakness at maximum exercise (103.4±25.9 kPa on the asymptomatic vs. 62.5±21.9 kPa in the symptomatic lower leg (p<0.001). Oscillography confirmed the SWE results by a decreased signal on the clinically symptomatic side.

Conclusion

SWE is suitable to detect muscle weakness during exercise in the symptomatic leg of mediasclerotic PAD patients. Since ABI measurements are usually invalid these patients with media sclerosis, shear wave elastography of lower limb muscles may contribute for a non-invasive diagnosis of symptomatic PAD. Larger randomized clinical trials are necessary to confirm our results.

Funding Acknowledgement

Type of funding sources: None.
The impact of statin treatment intensity after endovascular revascularization for lower extremity peripheral artery disease
Authors: Kim G S , Kim B K , Seo J K , Kim B O , Byun Y S
Published: October 2022

Purpose

There are few Asian studies on the clinical impact of statin intensity on clinical outcomes in patients with peripheral artery disease (PAD). This study investigated the clinical impact of statin intensity in patients with PAD after endovascular revascularization.

Material and methods

From April 2009 to June 2019, 376 patients with lower extremity PAD treated with endovascular revascularization were enrolled. They were classified into three groups according to statin intensity: no-statin, low-to-moderate intensity (LMI), and high-intensity (HI) groups. The primary outcomes were major adverse cardiovascular events (MACE) and major adverse limb events (MALE).

Results

During the 40-month follow-up, MACE occurred less in the HI and LMI groups than the no-statin group (11.4% vs. 16.0% vs. 39%, p<0.001). In the adjusted Cox models, the HI group had the lowest MACE (hazard ratio [HR]: 0.347; 95% confidence interval [CI] 0.144–0.834; p=0.018) and MALE (HR: 0.344; 95% CI 0.120–0.989, p=0.048), while the LMI group had fewer MACE (HR: 0.319; 95% CI 0.169–0.604, p=0.048) than the no-statin group. HI therapy was associated with better outcomes in terms of MALE (HR: 0.377; 95% CI: 0.208–0.684; p=0.001) and repeat revascularization (HR: 0.449; 95% CI: 0.243–0.830; p=0.011) than the LMI group after the inverse probability treatment weighting analysis.

Conclusions

HI and LMI statin use is associated with a significant reduction of MACE than no statin use. Regarding MALE, HI statin use was associated with better outcomes than no statin or LMI statin use.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2019R1G1A1100442).
Elevated Lipoprotein(a) levels increase Major Adverse Limb Event
Authors: Guedon A , De Freminville J B , Mirault T , Mohamedi N , Rance B , Fournier N , Paul J L , Messas E , Goudot G
Published: October 2022

Background

High lipoprotein(a) levels are involved in the development of cardiovascular events, as particularly in myocardial infarction, stroke, and peripheral artery disease. Studies assessing prognostic values of lipoprotein(a) levels on the lower limbs are lacking.

Purpose

The aim of our study was to look after a relationship between the lipoprotein(a) level and the incidence of major adverse limb events (MALE) defined as major amputation, peripheral artery endovascular revascularization or peripheral artery bypass.

Methods

We included 16,513 patients with lipoprotein(a) measurements from our clinical information system. Normal lipoprotein(a) level was under 50 mg/dL and we defined: high lipoprotein(a) level as a lipoprotein(a) level between 50 mg/dL and 134 mg/dL and very high lipoprotein(a) level as a lipoprotein(a) levels over 134 mg/dL, i.e the 95th percentile in this cohort. Accelerated Failure Time models were used to assess the relationship between the lipoprotein(a) level and the incidence of MALE retrieved from the patient's electronic record during a median (interquartile range) follow-up of 3.74 (1.07; 7.30) years after the lipoprotein(a) measurement. MALE was defined as the occurrence of one of the following during follow-up: aortofemoral bypass surgery, limb bypass surgery, percutaneous transluminal angioplasty revascularization of the iliac, or infrainguinal arteries; or major amputation above the forefoot. Secondary outcomes included individual components of the primary

Results

Median lipoprotein(a) level was 24 mg/dL (10; 60), with 70.3%; 24.7%; and 5.0% within normal; high and very high lipoprotein(a) level respectively. The 1-year MALE incidence was 2.2% [95% CI: 1.96; 2.51]; 2.60% [95% CI: 2.09; 3.10] and 4.54% [95% CI: 3.08; 5.98] among the normal, high and very high lipoprotein(a) level patients respectively. High and very high lipoprotein(a) levels were independently associated with an increased risk of MALE (adjusted Accelerated Failure Time Exponential Estimate) 0.43 [95% CI: 0.24; 0.78], p=0.01 and 0.17 [95% CI: 0.07; 0.40], p<0.001, respectively.

Conclusion

In this large cohort of unselected real-world hospital inpatients, higher lipoprotein(a) levels were independently associated with an increased risk of MALE. Though, lipoprotein(a) measurement shall be taken into account not only to refine the cardiovascular risk but also the lower limb risk of revascularization or amputation.

Funding Acknowledgement

Type of funding sources: None.
Ischemic stroke in France: are younger women at higher risk than men?
Authors: Alami O , Alami M
Published: October 2022

Introduction

Recent studies suggested that younger women were more likely to suffer from an ischemic stroke than men of the same age.

Purpose

Our aim is to confirm whether younger women in France are more exposed to ischemic strokes.

Methods

We compared male and female one-year hospitalization numbers for ischemic stroke in different age groups in France. We also used the French population data by sex and similar age group. Chi-square Tests of Homogeneity were used to assess statistical significance of the differences among men and women hospitalization numbers for each age group.

Results

Women in the age group 15–24 y-o experienced more ischemic strokes than men (151 hospitalizations for women vs 113 for men; p=0,0088). In the 25–34 y-o group, no differences were found between men and women (385 hospitalizations for men vs 370 for women; p=0,3497). In the 35–44 y-o group, women experienced less ischemic strokes than men (906 hospitalizations for women vs 1200 for men; p<0,0001). Women older than 85 y-o also had significantly more hospitalizations than men (15143 vs 6950; p=0,0073). All the other age groups showed a significative male predominance.

Conclusion

Younger women (15–24 y-o) are at higher risk of ischemic strokes than men of the same age in France. As far as ischemic stroke incidence is rising among young adults in France, an urgent awareness should be raised and further studies should focus on the possible etiologies.

Funding Acknowledgement

Type of funding sources: None.