bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary arterial hypertension in families with hereditary hemorrhagic telangiectasia: a 13-year follow-up study
Authors: Zhou Y.-P , Jiang X , Zhang Y.-X , Sun K , Lian T.-Y , Wu T , Hua L , Xu X.-Q , Jing Z.-C
Published: November 2020

Background

Pulmonary arterial hypertension (PAH) can occur in families with hereditary hemorrhagic telangiectasia (HHT), but it has not been well-characterized.

Purpose

This study sought to characterize the genetic defects, clinical and hemodynamic features, and outcomes of PAH patients in HHT families.

Methods

All HHT families with at least one case of PAH investigated in our center from January 2006 to December 2018 were enrolled in the study. We did whole-exome sequencing (WES) or whole-genome sequencing (WGS) to every proband and available family members. The clinical data, hemodynamic features and outcomes of PAH patients were reviewed.

Results

A total of 64 PAH patients in 57 families were enrolled. Only 7 (12.3%) families had more than one case of PAH. Activin-receptor-like kinase 1 (ALK-1) mutation and Endoglin (ENG) mutation were confirmed in 49 (86.0%) and 3 (5.3%) families and other 5 (8.8%) had no known mutation associated with HHT or PAH. The median age when PAH diagnosis was 22 [9–33] years and female was dominant (70.3%). Most patients (84.4%) had signs of HHT and anemia was recorded in 14 (21.9%) patients. Remarkably, these patients showed severely compromised hemodynamics with elevated mean pulmonary artery pressure (62 [51, 77] mm Hg) and pulmonary vascular resistance index (17.0 [11.2, 22.8] Wood units*m2). Also, impaired exercise capacity was recorded at diagnosis with decreased six-minute walking distance (410 [342–485] meters) and over half (54.7%) were in WHO functional class III or IV. The 1-, 3-, 5- and 10-year transplantation-free survival for the overall PAH patients was 95.0%, 75.9%, 67.1% and 36.4%, respectively. Anemia (HR: 4.24 [1.32–13.65], p=0.016) and CI <2.5 l/min/m2 (HR: 4.39 [1.20–16.09], p=0.026) were independent risk factors for mortality.

Conclusions

PAH in HHT families is a devastating condition characterized by a young age at PAH diagnosis, poor clinical status and outcomes mainly underlying ALK-1 mutation, which emphasizes the importance to pay attention to this group of patients.

Transplantation-free survival

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): The Beijing Natural Science Foundation (7181009), the National Key Research and Development Program of China (2016YFC0901502)
A novel causative gene variant, TNFRSF13B p.Gly76Ser, in patients with pulmonary arterial hypertension
Authors: Shinya Y , Hiraide T , Kataoka M , Momoi M , Goto S , Katsumata Y , Endo J , Sano M , Kosaki K , Fukuda K
Published: November 2020

Background

Pulmonary artery hypertension (PAH) is a poor prognostic disease. Some causative genes were reported as the PAH-associated genes. However, the pathogenetic variants in PAH-associated genes have not been identified in majority of patients with idiopathic PAH.

Purpose

Our aim was to investigate the new causative gene variants associated with PAH.

Methods

We performed whole-exome sequencing in 272 patients with idiopathic/heritable PAH. Structural analysis simulation was performed to define how the candidate gene variant affected the structure of protein.

Results

We identified the heterozygous substitution change of c.226G>A (p.Gly76Ser, rs146436713) in tumor necrotic factor receptor superfamily 13B gene (TNFRSF13B) (NM_012452.2) in 6 (2.2%) patients with idiopathic/heritable PAH, although the allele frequency of this rare variant is 0% in Integrative Japanese Genome Variation Database (control population database). Two of the six cases were blood relatives, although they did not have the known causative gene variants of PAH. One of these two relatives died of right heart failure despite the combination medical therapy, and her pathological anatomy demonstrated intimal thickening and medial hypertrophy in the pulmonary arteries, formation of plexiform lesions (Heath-Edwards classification grade V). Time-lapse images from structural analysis simulation showed the instability of N-terminal in the protein, which regulates the vascular inflammation, synthesized from TNFRSF13B p.Gly76Ser variant (Figure), suggesting that p.Gly76Ser variant may be involved in the development of PAH via aberrant inflammation in pulmonary vessels.

Conclusions

TNFRSF13B p.Gly76Ser variant is a candidate of causative gene variant for PAH.

Structural analysis of proteins

Funding Acknowledgement

Type of funding source: None
Usefulness of Suita score to predict deaths from aortic aneurysm rupture and aortic dissection in general population
Authors: Otaki Y , Watanabe T.W , Konta T.K , Watanabe M.W , Asahi K.A , Yamagata K.Y , Fujimoto S.F , Tsuruya K.T , Narita I.N , Kasahara M.K , Shibagaki Y.S , Iseki K.I , Moriyama T.M , Kondo M.K , Watanabe T.W
Published: November 2020

Background

Deaths from aortic aneurysm rupture and aortic dissection are the major causes of sudden death in Japan. Suita score developed in Japan, as well as Framingham risk score, is reportedly associated with ischemic heart disease. However, it remains undetermined whether Suita score is associated with aortic aneurysm rupture and aortic dissection deaths in general population.

Purpose

To examine whether Suita score could predict aortic aneurysm rupture and aortic dissection deaths in general population.

Methods and results

We used a database of 534,414 subjects (age 40–75 years) who participated in the annual “Specific Health Check and Guidance in Japan” check-up between 2008 and 2013. The univariate and multivariate Cox proportional hazard regression analyses demonstrated that Suita score was associated with both deaths from aortic aneurysm rupture and aortic dissection after adjustment for confounding risk factors. The C indices in Suita score for aortic aneurysm rupture deaths, aortic dissection deaths and ischemic heart disease deaths were 0.8295, 0.6689, and 0.7039, respectively. The C indices in Suita score to predict aortic aneurysm rupture deaths and aortic dissection deaths were significantly greater than those in Framingham risk score.

Conclusion

Suita score was superior to Framingham risk score and a feasible marker for aortic aneurysm rupture and aortic dissection deaths in general population, indicating that it could serve as an identification of high-risk subjects for aortic aneurysmal rupture and aortic dissection as well as ischemic heart disease.

Funding Acknowledgement

Type of funding source: None
Evaluation of left ventricular diastolic function in Marfan syndrome using speckle-tracking echocardiography
Authors: Garcia-Izquierdo Jaen E , Mingo Santos S , Cia Mendioroz X , Monivas Palomero V , Moreno Casado S , Navarro Rico S , Borrego Hernandez A , Torres Sanabria M , Martin Lopez C.E , Mitroi C , Gonzalez Mirelis J , Cavero Gibanel M.A , Segovia Cubero J , Forteza Gil A
Published: November 2020

Background/Introduction

Previous studies using conventional echocardiographic measurements have reported subclinical left diastolic dysfunction in patients with Marfan syndrome (MFS). Certain speckle-tracking echocardiography (STE) derived parameters have shown good correlation with invasive measurements of LV relaxation.

Purpose

To evaluate diastolic function in Marfan patients using STE-derived parameters along with traditional diastolic measurements and compare them with healthy controls.

Methods

We consecutively included 127 MFS patients with normal LV ejection fraction and no previous cardiovascular surgery or significant valvular regurgitation. We also studied 38 healthy controls (age and sex-matched). We performed LV and LA strain analysis using 2D STE (QLAB 10, Philips). Echocardiographic parameters recommended to assess diastolic function (according to ASE/EACVI 2016 guidelines) were also considered.

Results

Reported use of BB/ARB was 28/39% in MFS patients. According to current guidelines, all participants had normal diastolic function. MFS patients showed lower TDI e' velocities (septal and lateral) and higher average E/e' ratio compared to controls, but still within normal range. Regarding STE-derived measurements, LVGLS, EDLSR and PALS were significantly reduced in MFS. E/EDLSR ratio was higher among MFS patients, reflecting impaired LV relaxation. Interestingly, E/LVGLS was not different between both groups.

Conclusion

STE-derived parameters showed impaired LV relaxation in MFS patients compared to controls. Our results suggest that STE derived parameters can be markers of early diastolic dysfunction and provide a better insight into Marfan-related cardiomyopathy.

STE derived parameters

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Programa de Actividades de I+D de la Comunidad de Madrid
Ascending aorta: descending thoracic aorta ratio as an additional metric to early individually oriented diagnoses of abnormalities. A non-contrast enhanced cardiac CT study
Authors: Sosnowski M , Czekaj A , Brzoska J , Chromik K , Mlynarski R , Tendera M , Wojakowski W
Published: November 2020

Background

Coronary artery calcium (CAC) detection is the established indication for a non-contrast enhanced cardiac computed tomography (NCE-CCT). Other information, beyond CAC, can be derived from the NCE-CCT. Amongst them, data regarding thoracic aorta and its abnormalities might be of interest.

Aims

We aimed at examination whether mutual proportion of ascending aorta and descending thoracic aorta diameters (AAD:DAD ratio) could be diagnostically relevant.

Methods

This retrospective study included 4372 patients out of 5905 subjects undergoing NC-CCT during the last decade, in whom the thoracic aorta and pulmonary artery trunk were within common limits (AAD≤40mm, DAD<30mm, PAD<30mm). 213 persons without CVD risk factors and CAC=0 were qualified into control group (1), and 4159 patients with CVD risk factor(s) ≥1 into examined group (2) of. The range of AAD/PAD ratio normality was referenced from the group 1. In addition body mass index and CAC score were accounted for.

Results

The AAD/PAD ratio in control group was 1.35±0.22 with the normal range between 1.12 and 1.57. The 90th percentile values for AAD have been established. In patients with CAC=0, amongst those with normal BMI the increased AAD:DAD ratio (>1.57), indicating high AAD, was found in 18 /43 cases with AAD>90 percentile (41.2%) and in 21/498 with normal AAD (4.2%). The respective proportions in overweight patients were 23/86 (26.7%) and 12/694 (1.7%), and in obese patients 13/67 (19.4%) and 5/397 (1.3%). In patients with CAC>0, and normal BMI the increased AAD:DAD ratio was found in 10/38 cases with AAD>90% (26.3%) and in 14/458 with normal ascending aorta size (3.1%). Proportions in overweight patients were 23/92 (25.0%) and 15/859 (1.75%), while in obese patients were 17/107 (15.9%) and 13/579 (2.2%), resp. Normal AAD:PAD ratio in patients with established AAD increase (>90 percentile), irrespective of BMI, might suggest accompanying increase in PAD. Lower AAD:PAD ratio indicated a relative increase of the DAD. Mean values of AAD and DAD in relation to BMI and CAC categories along with their ratio are presented in table 1.

Conclusions

Evaluation of thoracic aorta in NC-CCT enhanced diagnostic scope of NCE-CCT. The AAD/DAD ratio, being independent of age, gender and body constitution, does not require adjustment, should be considered as additional metric for early diagnoses of thoracic aorta abnormalities well before absolute values reach the arbitrary cut-off levels.

Table 1

Funding Acknowledgement

Type of funding source: None
'Aorta code' implementation and preliminary results of a multidisciplinary protocol for patients with acute aortic syndrome
Authors: Ferrera Duran C , Vilacosta I , Perez-Villacastin J , Busca P , Carrero A , Martin Martinez A , Martin Sanchez F.J , Dominguez Garcia M.J , Martinez I , Cobiella J , Viana Tejedor A , Cortes Martinez A , Serrano J , Bas Villalobos M , Maroto-Castellanos L
Published: November 2020

Background

Expediting life-saving care for patients with acute aortic syndrome (AAS) through multi-disciplinary code protocols is a potential method to improve outcomes. Other code protocols for cardiovascular emergencies, such as ST-elevation myocardial infarction and stroke have shown excellent results.

Aim

To examine the implementation and preliminary results of a code protocol “Aorta Code” for patients with AAS in a healthcare framework of a 4-hospital network in our city by reviewing the number of patients detected, patient's transference time, aortic surgery and patient's outcome during a trial period of 10 months (April 2019-January 2020). A comparison with a previous 2-year period with standard of care management of AAS was performed.

Methods

“Aorta Code” uses a specific diagnostic algorithm to improve detection of patients with AAS at the emergency room, facilitates their quick transfer to the referral hospital by activating a paging system, and places acute cardiovascular care unit, operating room and surgeons specialized in aortic pathology on standby.

Results

Compared to a previous 2-year period (2017–2018) (group I), the current implementation of “Aorta Code” in a period of 10 months (group II) in our 4-hospital network involving the healthcare of 1.100000 inhabitants resulted in the detection of more patients with AAS (group-I: n=18 patients (0.8 patients/month), group-II: n=19 patients (1.9 patients/month); p=0.013). AAS detection in secondary hospitals importantly increased (33.3% vs 63.8%, p=0.07). The “Aorta Code” achieved a significant decrease in patient's transference time to referral hospital (group-I: median 259 min (IQR 150–1911), group-II: median 129 min (IQR 95.5–167.25); p=0.035). There was a marked reduction in the number of surgeons involved in the “Aorta Code” (group-I= 7 cardiac, 6 vascular, group-II= 2 cardiac, 2 vascular). Thirty-day mortality was lower in group-II in the whole AAS cohort (group-I= 22.2%, group-II= 12.5%; p=0.660) and in type A AAS (28.6% vs 18.2%, p=0.661). Misdiagnosis rate (false-calls): 11 patients (7 of them with non-acute aortic disease).

Conclusion

“Aorta Code” facilitates detecting patients with AAS at the emergency room, speeds them to the referral hospital center, allows patients to be treated by surgeons specialized in aortic surgery and improves patient's outcome. Further prospective studies examining the utility of “Aorta Code” are warranted.

Funding Acknowledgement

Type of funding source: None
Clinical importance and configuration of collateral vessel systems in patients with Takayasu arteritis or with thymoma visualized by three-dimensional volume rendering computed tomographic angiography
Authors: Funabashi N , Kobayashi Y
Published: November 2020

Background

Collateral vessels form after gradual blood vessel occlusion. We speculate that in Takayasu arteritis (TA) and thymoma patients, before planning surgical procedures, a complex artery/venous system should be examined using three dimensional (3D) volume rendering computed tomographic (CT) angiography.

Purpose

To seek the clinical importance and actual complex configuration of collateral vessel systems in patients with TA or with thymoma using 3D volume rendering CT angiography with special acquisition method.

Methods

We performed 3D CT angiography in patients with Takayasu arteritis (TA) with occluded arteries (N=6) or thymoma (N=2) with occluded superior-vena-cava (SVC), respectively. For CT angiography in thymoma patients, diluted (1/4) iodinated-contrast was injected in right and left medial cubital-veins simultaneously, and images acquired 10 seconds after contrast-injection.

Results

Occluded and collateral-arteries (TA group) and occluded SVC and collateral-veins (thymoma group) were successfully visualized (Figures a-h). Collateral-arteries form from the inferior mesenteric artery (Figure a) or de novo arteries from the abdominal aorta (Figure b) after superior mesenteric artery occlusion (Figure c, d). In patients with thymoma, an SVC thymoma disrupts venous return in the neck and upper extremities; a complex venous system forms on the abdominal surface (Figure e-h).

Conclusion

In TA and thymoma patients, before planning surgical procedures, a complex artery/venous system should be examined using 3D volume rendering CT angiography. For CT in thymoma, diluted (1/4) iodinated contrast should be injected in both medial cubital veins, and images should be acquired 10 seconds after contrast-injection.

3D volume rendering CT angiography

Funding Acknowledgement

Type of funding source: None
Development of a three-dimensional prognostic score for patients with symptomatic peripheral artery disease: PAD3D score
Authors: Dopheide J.F , Adam L , Gahl B , Papac L , Kaspar M , Baumgartner I , Drexel H
Published: November 2020

Background

Peripheral artery disease (PAD) is a high-risk condition for cardiovascular Events, but no individual prognosis assessment exists.

Objectives

We aimed to establish an individual, clinically useful risk score based on the combined predictive value for mortality of (i) age, (ii) severity of PAD, and (iii) extent of atherosclerosis (PAD3D).

Methods

1310 patients with symptomatic PAD underwent follow-up for a mean of 50±26 months. We randomly subdivided the cohort into test and validation cohort. All-cause and cardiovascular mortality were prospectively analysed for the t PAD3D score and in combination with classical risk factors (PADRF).

Results

For test and validation cohort (n=655), all-cause and cardiovascular mortality was precisely predicted (both p<0.001) by the PAD3D score (Fig. 1 A+B). The additional inclusion of classical risk factors did not increase discrimination (Fig 1 C+D) compared to PAD3D score, as AU-ROCs were similar for both scores at 12 and 24 months (Fig. 2). Thus, the addition of classical risk factors did not further improve the prognostic value. The PAD3D score provides a risk gradient of a 4.5-fold increase in all-cause and cardiovascular mortality.

Conclusions

We established a score for precise prediction of all-cause and cardiovascular mortality. The PAD3D score promises to allow for personalized goals in risk intervention.

All-cause and cardiovascular mortality

Funding Acknowledgement

Type of funding source: None
Meta-analysis comparing impact of age, sex and renal function on the efficacy and safety of new oral anticoagulants vs. vitamin K antagonists for the treatment of acute venous thromboembolisms
Authors: She J , Zhuo B.Z
Published: November 2020

Background

New direct oral anticoagulants (NOACs), as a preferable treatment option for acute venous thromboembolism (VTE) have been recommended with practical advantages as compared to Vitamin K antagonists (VKAs) in clinical practice.

Purpose

In our study, we performed a meta-analysis to determine the efficacy and safety of NOACs vs. VKAs in patients with different age, sex and renal function for the treatment of VTE.

Methods

Electronic databases (accessed October 2019) were systematically searched to identify RCTs evaluating apixaban, dabigatran, edoxaban, and rivaroxaban versus VKAs for the treatment of acute venous thromboembolism.

Results

NOACs was associated with a borderline higher efficacy in female (OR 0.79, 95% CI 0.62–1.02), and a significantly higher efficacy in patients with age more than 75 (OR 0.51, 95% CI 0.32–0.80) and creatinine clearance less than 50 mL/min (OR 0.57, 95% CI 0.32–0.99). NOACs also show advantage in terms of major or clinically relevant non-major bleeding in male (OR 0.72, 95% CI 0.60–0.86), and patients with creatinine clearance more than 50 mL/min (OR 0.75, 95% CI 0.67–0.84).

Conclusions

NOACs have exhibited clinical preference among patients with acute VTE as compared to VKA with significantly decreased thrombosis events and lower bleeding complications, especially in patients with age more than 75 and creatinine clearance less than 50 mL/min.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): This study was supported by the National Natural Science Foundation of China (81800390) and the Natural Science Foundation of Shaanxi province (2018KW067).
Effects of PCSK9 inhibitor on adverse limb outcomes in patients with critical limb ischemia
Authors: Sato Y , Uzui H , Aiki Y , Aoyama D , Yamaguchi J , Nodera M , Shiomi Y , Hasegawa K , Ikeda H , Tama N , Fukuoka Y , Morishita T , Ishida K , Miyazaki S , Tada H
Published: November 2020

Background

The proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9-I), evolocumab, reduced the risk of cardiovascular event in patients with peripheral artery disease in FOURIER trial. However, the effects of evolocumab on favorable limb outcomes in patients with critical limb ischemia (CLI) is still unclear.

Purpose

The aim of this study was to evaluate the impacts of evolocumab on favorable limb outcomes and lipid profile in patients with CLI.

Methods

This was a single center, prospective observational study. A total of 39 patients with CLI were enrolled between November 2016 to May 2019. The subjects were divided into 2 groups based on evolocumab administration: evolocumab-treated group: E group (mean 69.4±11.7 years, n=14) and evolocumab non-treated group: Non-E group (mean 74.0±8.8 years, n=25). Baseline characteristics were assessed at admission. Lipid profile was evaluated at admission, 1, 3, 6, 12 and 18 months. The primary outcome was defined 18-month amputation-free survival (AFS). The secondary outcomes were defined 18-month overall survival (OS) and wound-free limb salvage. Mean follow-up period was 18±11 months.

Results

The patients in E group had greater reduction in levels of LDL cholesterol and non-HDL cholesterol than those in Non-E group over time. The reduction in MDA-LDL level was maintained at 1, 3, 6, 12 months, respectively. The 18-month AFS rate in the E-group was significantly higher than those in the Non-E group (log-rank p=0.02). The patients receiving evolocumab had a lower hazard regarding AFS (hazard ratio, 0.12; 95% confidence interval, 0.02–0.94; P=0.043) and a higher proportion of wound-free limb salvage at 12 months (E group [92%] vs Non-E group [57%], P=0.034) and 18 months (92% vs 52%, P=0.03). Otherwise, evolocumab administration was not associated with 18-month OS (log-rank p=0.053).

Conclusions

Evolocumab administration may be associated with the favorable outcome of 18-month AFS in the patients with CLI. Additionally, long-term administration of evolocumab over 12 months may improve wound-free limb salvage.

Effects of evolocumab on limb outcomes

Funding Acknowledgement

Type of funding source: None
Sodium-glucose cotransporter-2 inhibitors and their combination with glucagon like peptide-1 receptor agonists improve endothelial glycocalyx and arterial stiffness in type-2 diabetes
Authors: Ikonomidis I , Pavlidis G , Thymis J , Birba D , Kalogeris A , Kousathana F , Kountouri A , Balampanis K , Parissis J , Andreadou I , Katogiannis K , Dimitriadis G , Bamias A , Iliodromitis E , Lambadiari V
Published: November 2020

Background/Introduction

Type-2 diabetes mellitus (T2DM) is associated with endothelial and arterial dysfunction.

Purpose

We investigated the effects of insulin, glucagon like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i)and their combination on endothelial and arterial function of T2DM patients.

Methods

A hundred-sixty T2DM patients (age: 58±10 years) were randomized to insulin (n=40), liraglutide (n=40), empagliflozin (n=40) or their combination (GLP-1RA+SGLT-2i) (n=40)as add-on to metformin. We measured at baseline, 4 and 12 months post-treatment: a) perfused boundary region (PBR) of the sublingual arterial microvessels (ranged from 5 to 25μm) using Sideview Darkfield imaging. Increased PBR indicates reduced glucocalyx thickness, b) pulse wave velocity (PWV-Complior), central systolic blood pressure (cSBP) and augmentation index (AI) of the aortic pulse wave.

Results

Twelve months post-treatment, all patients improved PBR, PWV and AI (p<0.05). GLP-1RA, SGLT-2i and their combination showed a greater reduction of PBR, PWV and cSBP than insulin, despite a similar HbA1c reduction (p<0.05). SGLT-2i or combined therapy with GLP-1RA and SGLT-2i showed a greater decrease of PWV (−10.1% and −13% vs. −3.6% and −8.6%) and cSBP (−3% and −5.5% vs. −0.8% and −1.5%)than insulin or GLP-1RA (p<0.05 for all comparisons). GLP-1RA or GLP-1RA+SGLT-2i provided a greater decrease of AI (−42.7% and −48.6% vs. +6.2% vs. −3.8%) compared with insulin or SGLT-2i (Table). The dual therapy showed the greatest effect on measured markers in patients with LVEF <55% (p<0.05).

Conclusions

Twelve-month treatment with SGLT-2i and its combination with GLP-1RA, showed a greater improvement on arterial elastic properties than GLP1RA or insulin treatment in T2DM. The combined therapy as second line was superior to either insulin, or GLP-1RA and SGLT-2i separately.

Funding Acknowledgement

Type of funding source: None
Endovascular treatment of peripheral artery disease is associated with improved central hemodynamics and ventricular function
Authors: Messiha D , Halfmann L , Azizy O , Steinmetz M , Rassaf T , Rammos C
Published: November 2020

Background

Peripheral artery disease (PAD) is a major manifestation of atherosclerosis and a risk factor for morbidity and mortality. PAD itself is associated with increased arterial stiffness with impact on cardiac functions. Previous studies have demonstrated that augmentation index (AIx) and central blood pressure (CBP) correlate with increased cardiovascular mortality. This mechanism has been described as arterio-ventricular (AV) coupling with altered ventricular afterload and a depressed ventricular function, measured by global longitudinal strain (GLS). The impact of PAD-related endovascular treatment on arterial stiffness, central hemodynamics and potential impact on AV coupling has not been elucidated until now.

Purpose

Aim of the study was to investigate, if endovascular treatment of PAD improves cardiac function via enhanced central hemodynamics and AV coupling.

Methods

To this aim 77 patients with known symptomatic PAD who underwent interventions in the iliac and femoropopliteal arteries were included in a cross-sectional study. AIx, CBP and GLS were determined using dedicated waveform analysis and echocardiography before and after endovascular treatment.

Results

Mean age was 65.1±10.4 years with 66.2% male patients. Symptoms were classified by Fontaine classification (stage IIb 80.7%, stage III 5.8% and stage IV 13.5%). Iliac vessel intervention was performed in 16 and femoropopliteal intervention in 61 cases. A stentless approach was feasible in 55 patients with DCB treatment and atherectomy.

After endovascular treatment, peripheral perfusion was enhanced (ABI 0.45±0.6 vs 0.81±0.5, p<0.0001). Moreover, central hemodynamics were improved (AIX 33.7±3% vs 27.9±2%, p=0.0008; AP 17.8±2 mmHg vs 14.0±2 mmHg, p=0.0004; central PP 52.4±6 mmHg vs 46.4±6 mmHg, p=0.0001). Impressively, left ventricular function was also significantly improved (GLS −15.7±2.3% vs −17.1±2.8%, p=0.005) with an improvement in AV coupling (PWV/GLS ratio −0.58m/sec% vs −0.56m/sec%, p<0.01).

Conclusion

Our results demonstrate that endovascular treatment of the peripheral vessels is associated with an improvement of central hemodynamics and left ventricular function via enhanced AV coupling. These prognostic relevant markers of cardiovascular disease could point to an overall potential mortality benefit through PAD treatment. Further investigation of the underlying mechanisms of AV coupling in the setting of endovascular treatment of PAD with impact on cardiovascular mortality is needed in this high-risk population.

Funding Acknowledgement

Type of funding source: None
Clinical usefulness of Lipoprotein(a) for the prevalence and severity of peripheral artery disease among patients with acute coronary syndrome
Authors: Okubo R , Aikawa H , Matsumoto S , Noike R , Yabe T , Nakanishi R , Amano H , Toda M , Ikeda T
Published: November 2020

Background

Lipoprotein(a) [LP(a)] is known to be a robust lipid marker associated with cardiovascular events. Though coronary artery disease and peripheral artery disease (PAD) are often coexist, little is known about the relationship between LP(a) and PAD among patients with acute coronary syndrome (ACS).

Purpose

The purpose of this study is to examine if LP(a) is of predictive value for PAD among ACS patients in Japanese population.

Methods

Of consecutive 238 ACS patient who received successful primary PCI, a total of 175 patients were enrolled in the current study. We excluded the patients who received hemodialysis (n=10), required multidisciplinary treatment (n=36) and incomplete data (n=17). PAD was diagnosed as ankle brachial index <0.9. Multiple lipid biomarkers [LP(a), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), malondialdehyde-modified LDL (MDA-LDL), docosahexaenoic acid and arachidonic acid] were compared between patients with PAD (n=21) and without PAD (n=154). Further, multivariable logistic regression models were used to assess if LP(a) was associated with PAD. In addition, serum LP(a) level were compared between 3 groups according to pattern of PAD [none (n=154), unilateral (n=10) and bilateral PAD (n=11), respectively].

Results

Compared to patients without PAD, those with PAD were older (74.4 vs. 65.4 years, p=0.003), and had a higher prevalence of chronic kidney disease (CKD) (61.9% vs. 20.1%, p<0.001), diabetes mellitus (DM) (66.7% vs. 27.3%, p<0.001). Serum LP(a) level was significantly higher in patients with PAD (36.4 vs. 18.5 mg/dl, p<0.001), whereas LDL-C and MDA-LDL were significantly lower in PAD (92.0 vs. 109.5 mg/dl, p=0.015 and 98.6 vs. 119.5 mg/dl, p=0.046, respectively). After adjusting for LDL-C and MDA-LDL, LP(a) >30 mg/dl was independently associated with a presence of PAD (OR 5.67, 95% CI 2.09–15.4, p=0.0006). When adjusting for CKD and DM in a different model, LP(a) >30 mg/dl was similarly associated with PAD (OR 4.98, 95% CI 1.66–14.9, p=0.004). Serum LP(a) levels were significantly higher in bilateral PAD group compared to none PAD group (Figure).

Conclusion

LP(a) was a useful lipid biomarker for the prevalence and severity of PAD among patients with ACS in Japanese population.

Funding Acknowledgement

Type of funding source: None
Assessment of internal carotid artery stenosis and results of carotid stenting by angiography compared with intravascular ultrasound
Authors: Stechovsky C , Hajek P , Roland R , Horvath M , Veselka J
Published: November 2020

Background/Introduction

Intravascular imaging is commonly used in coronary interventions and improves outcomes. On the contrary, it is almost unrecognized for the guidance of carotid stenting (CAS).

Purpose

The aim of this study was to compare quantitative angiography (QA) and intravascular ultrasound (IVUS) in the assessment of the severity of carotid stenosis and residual stenosis in patients undergoing CAS and to provide reference values for IVUS measurements of the internal carotid artery (ICA) in the European population.

Methods

IVUS imaging was performed during 151 CAS procedures in 140 patients from April 2013 to December 2019. In total 162 self-expanding stents of different design were implanted (66% closed-cell, 22% open-cell, 8% hybrid, 4% double layer micromesh stents). IVUS was used to measure distal reference diameter and area of ICA, minimal luminal diameter (MLD) and minimal luminal area (MLA) before and after CAS. IVUS and QA were used to measure relative stenosis area (stenosis) at baseline and relative residual stenosis area (residual stenosis) after CAS. Relative stenosis area was calculated as [1 − (MLA / distal reference area)] x 100.

Results

Mean (±SD) distal reference diameter of ICA was 4.5±0.8 mm. MLD increased from 1.9±0.4 mm to 3.6±0.6 mm after CAS (p<0.001). MLA increased from 3.9±1.7 mm2 to 12.0±3.4 mm2 after CAS (p<0.001). Stenosis measured by QA and IVUS was 84±9% and 76±13% respectively (p=0.01). There was a moderate correlation (Pearson's correlation coefficient r=0.575; p=0.01) between QA and IVUS measurement of ICA stenosis severity. Residual stenosis measured by QA and IVUS was 12±10% and 40±16% (p<0.001) respectively with only weak correlation (r=0.433; p<0.001) between the two methods.

Conclusion

Angiography slightly overestimates stenosis of internal carotid artery and substantially underestimates residual stenosis after CAS compared to IVUS. Angiography alone is inaccurate in the assessment of ICA stenosis and results of carotid stenting.

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): University Hospital Motol
Are there mortality differences between men and women in all types of intracranial hemorrhages: subarachnoid, intraparenchymal and subdural? An analysis of the Spanish population
Authors: Fernandez De Bobadilla Osorio J , Rey-Blas J.R , Gonzalez-Aguado N , Fuentes B , Masedo P , Iniesta A , Pena-Conde L , Rivero B , Severo A , Juarez V , Lopez De Sa E , Poveda D , Arbas E , Tebar D , Lopez-Sendon J.L
Published: November 2020

Objectives

There are 3 types of intracranial hemorrhage (ICH): 1) subarachnoid hemorrhage (SAH), CIE10:I60; 2) intraparenchymal hemorrhage (IPH), I61 and 3) subdural hemorrhage (SDH) I62. Epidemiological data on this field are scarce in Mediterranean countries. Our goal was to determine whether the relationship of ICH mortality with gender and age was different for the 3 types of HIC.

Methods

Data were retrospectively obtained from the Spanish National Institute of Statistics. Deaths/100.000 population of SAH, IPH and SDH were assessed for the entire Spanish population since 2008 to 2017 (n=46,527,039). Year 2017 was the last available for analysis. Incidence was analyzed for men and women and for age strata (<1 years of age, 2–10, 11–20, 21–30, 31–40, 41–50, 51–60, 61–70, 71–80; >80).

Results

In order to fit in the abstract space, only data of 2017 are presented, although years 2008 to 2017 were also analyzed and results were similar. Mortality/100,000 of IPH stayed very low under 40 years of age and then grew exponentially in both, men and women, and was significantly higher for men for all age strata. Mortality of SDH was much lower but behaved in a similar way: exponential growth since 40s and lower incidence in women. SAH behaved differently: it started to be significant since 20 years of age and there were no gender differences.

Conclusion

Mortality of intraparenchymal and subdural hemorrhage increases exponentially since 40 years of age and is lower in women. On the contrary, mortality of subarachnoid hemorrhage increases earlier and there are no gender differences.

Death/100.000 intracranial hemorrhage

Funding Acknowledgement

Type of funding source: None
Endovascular treatment in acute ischemic stroke: collaboration between neurologists and cardiologists in a single center
Authors: Petrov I , Klissurski M , Stankov Z , Tasheva I , Polomski P
Published: November 2020

Background

Several randomized trials have indicated a benefit from endovascular therapy in acute ischemic stroke (AIS) patients. In some centers, interventional cardiologists with previous large carotid stenting experience can play significant role for this treatment.

Objectives

We present retrospective analysis of prospectively collected data of endovascular treatment of stroke (EVTS) performed by interventional cardiologists in collaboration with neurologists in 46 patients in single center.

Methods

Between 2014 and 2017 46 consecutive AIS patients underwent EVT, men 69.7% (7 with posterior circulation stroke and 5 with wake-up stroke), with mean age 64.6±13 years and average National Institutes of Health Stroke Scale (NIHSS) score of 12.2±5 at presentation. During the same period of time 20 patients, 16 men, at mean age 69.4±12, and NIHSS score 11.8±7 received IVT. In the EVT group two methods were applied:

Method 1, Supraselective intra-arterial thrombolysis (IAT) alone or IAT plus balloon angioplasty (PBA);

Method 2, Aspiration with Penumbra aspiration system (PAS) or Combination of PAS plus low dose IAT.

Results

The mean symptoms onset-to-treatment (needle) time (ONT) in the EVT group was 221.7±121.5 minutes, and 185.5±34.9 in the IVT group (p=0.19T). Conscious sedation and local anesthesia was used in 84.7% of the patients (40), general anesthesia in 15.2%; preprocedural MRI was performed in 58.7% and CT in 71.7% of the patients. In the EVT group successful reperfusion (TICI 2b-3 flow) was achieved in 35 (76.1%) patients: in 73.9% with Method 1 and in 86.7% with Method 2 (p=0.44). Poor or no recanalization (TICI 0–1-2a) was observed in 26.1%. Twenty six of 46 patients (56.5%) treated with endovascular methods and respectively 9 (45%) with IVT demonstrated favorable clinical outcome of mRS score 0–2 at 90 days (p=0.91). The overall 3-month mortality was 15.2%, 13% after EVT and 20% after IVT (p=0.48).

Conclusions

Our initial experience with EVT of AIS performed by trained cardiologists with carotid experience is encouraging, with a relatively moderate to high rate of successful angiographic recanalization and good clinical results.

Funding Acknowledgement

Type of funding source: None
Efficacy of rivaroxaban compared to standard of care in preventing ischemic stroke in adults with coronary or peripheral vascular disease: an integrated analysis using patient-level data
Authors: Barnathan E.S , Deng H , Sun X , Dong X , La Police D , Suh E , Yuan Z , Berlin J.A
Published: November 2020

Background

Ischemic stroke is a leading cause of morbidity and mortality. Rivaroxaban has been evaluated in multiple studies of patients with coronary artery disease and/or peripheral artery disease (CAD/PAD) in which ischemic stroke was assessed.

Purpose

To determine the efficacy of rivaroxaban compared with standard of care (SOC) in reducing ischemic stroke in adults with CAD/PAD.

Methods

Randomized, active- or placebo-controlled Phase 2 or 3 studies evaluating rivaroxaban (2.5 mg twice daily) in adults with CAD/PAD in which ischemic stroke was collected as an efficacy endpoint were included using patient-level data. All stroke was also evaluated as a secondary outcome. ISTH major bleeding (MB) was assessed on treatment + 2 days. Hazard ratios (HR) and p-values for the treatment effect were estimated using Cox proportional hazards models and log-rank tests, respectively, with study as the stratification factor. Mixed effect Cox models (frailty models) were used with treatment as the fixed effect and study as the random effect. Cumulative risk of time-to-first event was assessed using the Kaplan-Meier method.

Results

Six studies were included: ATLAS-1, ATLAS-2, COMPASS, COMMANDER HF, GEMINI ACS1 and PIONEER AF-PCI (n=38,283). Compared with SOC, rivaroxaban significantly reduced the risk of ischemic stroke (HR, 0.63, 95% CI, 0.52–0.77, P<0.001) and all stroke (HR, 0.71, 95% CI, 0.59–0.84, P<0.001), without significant heterogeneity. The frailty model results were consistent. The risk of MB was significantly higher with rivaroxaban compared with SOC (HR, 1.58, 95% CI, 1.37–1.83, P<0.001).

Conclusion

Rivaroxaban (2.5 mg twice daily) significantly reduced ischemic stroke and all stroke compared with SOC in patients with acute or chronic CAD/PAD while increasing MB.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Janssen Research and Development
Stroke prevention by Non-vitamin K Oral Anticoagulant (NOAC) agents in the absence of atrial fibrillation: meta-analysis of randomized control trials
Authors: Lander K , Thakeria P , Andrew H , Nayyar S
Published: November 2020

Background

Anticoagulation to prevent stroke is a mainstay of atrial fibrillation (AF) management. Patients with established cardiovascular disease (CVD) may have conditions that fulfil Virchow's triad for thrombogenesis even in sinus rhythm. Previous investigation into the benefit of warfarin compared to placebo or antiplatelet drug in sinus rhythm found a reduction in stroke rates, but with an increase in bleeding. The efficacy and safety of non-vitamin K oral anticoagulant (NOAC) agents has not been studied.

Purpose

To assess the safety and efficacy of NOAC agents in patients without AF.

Methods

An electronic database search for randomized controlled trials that evaluated a NOAC and control drug (placebo or antiplatelet) in non-AF patients with CVD was conducted up until 1 September 2019. The primary efficacy and safety outcomes were ischemic stroke and major bleeding, respectively. The net clinical benefit (NCB) was calculated as a weighted sum of rate differences of ischemic stroke and major bleeding. Groups were stratified according to intensity of anticoagulation (full vs. low dose NOAC).

Results

Twelve randomized controlled trials were identified with a total of 83,008 patients (50,617 on NOAC, 32391 on control drug; mean age 66±2.7 years). CVD included coronary artery disease (78.3%), hypertension (73.7%), diabetes mellitus (34.7%), peripheral arterial disease (30.3%), previous stroke (21.7%), renal disease (22.9%) and heart failure (18.4%). Over a mean follow-up of 17.3 months, 1347 (1.6%) ischemic strokes occurred. Use of NOAC was associated with 28% reduction in ischemic stroke (odds-ratio [OR] 0.72, 95% confidence-interval [CI] 0.60 to 0.87; 1.1 vs. 1.8 events per 100-person years), with numbers needed to treat of 145 patients to prevent one stroke. Major bleeding was increased nearly 2-fold (OR 1.83, 95% CI 1.46 to 2.29; 2.1 vs. 1.0 events per 100-person years). The NCB demonstrated overall harm with the use of NOAC agents in this patient population (NCB = −0.28, 95% CI: −0.79 to 0.23). Use of full dose NOAC was widely unsafe (NCB = −0.35, 95% CI: −1.25 to 0.54) and low dose NOAC approached null therapeutic safety advantage (NCB = −0.06, 95% CI: −0.47 to 0.35).

Conclusion

Patients with CVD are at increased of ischemic stroke in the absence of AF. The use of NOAC agents in this non-AF population reduces rate of ischemic stroke however overall risk of bleeding exceeds antithrombotic benefit. Low-dose NOACs demonstrate a neutral NCB suggesting a point of clinical equipoise and deserve further scrutiny.

Ischemic stroke vs major bleeding

Funding Acknowledgement

Type of funding source: None
Stroke etiology by occlusion site – data from the PRAGUE 16 study
Authors: Vavrova J , Koznar B , Peisker T , Vasko P , Rohac F , Sulzenko J , Kroupa J , Stetkarova I , Mengozzi L , Widimsky P
Published: November 2020

Background

Catheter-based thrombectomy (CBT) is the most effective treatment for acute ischemic stroke. Endovascular treatment program - Prague 16 was established in tertiary university hospital in 2012 as result of close cooperation among cardiologists, neurologists and radiologists. The aim of this substudy is to analyze relationship between stroke localization and its etiology.

Methods

Single center, prospective registry of consecutive patients (pts) treated by CBT for acute ischemic stroke. Total of 214 pts (median 70 ys, range 21–92 ys, men 53.3%) were enrolled between 2012 and 2018. During hospitalization and subsequent 3-months follow-up, all pts were carefully examined (at least 48 hours ECG monitoring, CT angiography, carotid arteries sonography, transthoracal/ transoesofageal echocardiography) to determine the most likely stroke etiology.

Results

Relative frequency of strokes based on occlusion site and their etiology is shown in table below. In half of all strokes (50.9%), stroke etiology was assumed to be cardioembolic, mostly due to atrial fibrillation (89.0%). Isolated middle cerebral artery (MCA) occlusion and T-type strokes were mostly caused by cardioembolism (66.3% and 58.9%), unlike vertebrobasilar (VB) strokes, isolated internal carotid artery (ICA) occlusion/tight stenosis and tandem occlusion strokes were mostly atherotrombogenic (53.8%, 44.8% and 55.6%).

Conclusions

The majority of strokes with MCA and T-type occlusion was caused by cardioembolization, mostly due to atrial fibrillation. ICA occlusion, tandem occlusion and VB occlusion strokes were mostly caused by atherotrombosis.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Charles University Research Project Progress Q35
Safety of early anticoagulation in patients treated with urgent reperfusion for acute ischemic stroke related to non-valvular atrial fibrillation
Authors: Giustozzi M
Published: November 2020

Background

The optimal timing for starting anticoagulation after an acute ischemic stroke related to non-valvular atrial fibrillation (AF) remains a challenge, especially in patients treated with systemic thrombolysis or mechanical thrombectomy.

Purpose

We aimed to assess the rates of early recurrence and major bleeding in patients with acute ischemic stroke and AF treated with thrombolytic therapy and/or thrombectomy who received oral anticoagulants for secondary prevention.

Methods

We combined the dataset of the RAF and the RAF-NOACs studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and AF treated with either vitamin K antagonists (VKAs) or new oral anticoagulants (NOACs). Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion.

Results

A total of 2,159 patients were included in the RAF and RAF-NOACs trials, of which 564 patients (26%) were treated with urgent reperfusion therapy. After acute stroke, 505 (90%) patients treated with reperfusion and 1,287 out of the 1,595 (81%) patients not treated with reperfusion started oral anticoagulation. Timing of starting oral anticoagulation was similar in reperfusion-treated and untreated patients (13.5±23.3 vs 12.3±18.3 days, respectively, p=0.287). At 90 days, the composite rate of recurrence and major bleeding occurred in 37 (7%) of patients treated with reperfusion treatment and in 139 (9%) of untreated patients (p=0.127). Twenty-four (4%) reperfusion-treated patients and 82 (5%) untreated patients had early recurrence while major bleeding occurred in 13 (2%) treated and in 64 (4%) untreated patients, respectively. Seven patients in the untreated group experienced both an ischemic and hemorrhagic event. Figure 1 shows the risk of early recurrence and major bleeding over time in patients treated and not treated with reperfusion treatments. The use of NOACs was associated with a favorable rate of the primary outcome compared to VKAs (Odd ratio 0.4, 95% Confidence Interval 0.3–0.7).

Conclusions

Reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with AF-related acute ischemic stroke who started anticoagulant treatment.

Figure 1

Funding Acknowledgement

Type of funding source: None