bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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&lt;0.05). Patients with no arterial event were more frequently relatives (73%) than probands (27%) (p&lt;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

Abstract

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&lt;0.0001) one day afterward. After 6 months, the ABI of 0.8±0.27 (n=49; p&lt;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

Abstract

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&lt;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

Abstract

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 &lt;60 years old (group I), 194 (32.0%) were 60–69 years old (group II), and 176 (29.1%) were &gt;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 &gt;69 years (group III) compared with age &lt;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

Abstract

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&lt;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

Abstract

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&lt;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

Abstract

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&lt;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

Abstract

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&lt;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

Abstract

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&lt;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.