bluuebunny/crossref_metadata_2025 huggingface dataset:
Macitentan for pulmonary arterial hypertension related to repaired congenital heart disease: real-world UK experience
Authors: Constantine A , Condliffe R , Clift P , Jansen K , Wort S J , Moledina S , Dimopoulos K
Published: October 2022

Introduction

Patients with pulmonary arterial hypertension (PAH) following congenital heart disease (CHD) repair are an emerging population at increased risk of complications. Small numbers of such patients have been included in studies evaluating the efficacy of macitentan, but since obtaining a license for use in this population, limited real-world data have been published.

Purpose

To describe the safety and efficacy of macitentan therapy in a population of adults with repaired PAH-CHD.

Methods

We conducted a retrospective observational study of patients with repaired PAH-CHD newly started on macitentan in 2 UK specialist centres between 2014 and 2020. Clinical variables, including WHO functional class (FC), 6-minute walk (6MW) or incremental shuttle walk (ISW) distance, and EMPHASIS-10 score were recorded prior to and after initiation of macitentan therapy.

Results

Overall, 49 patients were included, 63.3% female, median age 40.8 [26.7–53.7] years at initiation of macitentan therapy. Macitentan was started as part of the initial PAH therapeutic regimen in 18 (36.7%) and was an add-on to existing therapy in 31 (63.3%) patients, of whom over a third (35.5%) were switched from another endothelin receptor antagonist. At the time of therapy initiation, most patients (68.4%) were in WHO functional class (FC) III, while 26.3% were in FC II and 5.3% in FC I. Baseline 6-minute walk distance (n=31, 72.1%) was 355.0 [263.5–461.2] m and incremental shuttle walk distance (n=12, 27.9%) was 220.0 [175.0–302.5] m. EMPHASIS-10 score (n=39) was 24 [10–36]. After 12.7 [9.8–16.1] months of macitentan therapy, objective exercise capacity improved by 11.8 [−4.3–36.9]% (p=0.01). Health-related quality of life improved by at least 5 points in 41.9% of patients, but there was no significant change in quality of life score in the overall group (0.0 [−20.3–18.1]% change, p=0.78). Macitentan therapy was stopped in 4 (8.2%) patients due to an adverse event or patient choice, and 5 (10.2%) due to clinical worsening or absence of clinical improvement. At 1 year following macitentan initiation, 6 (12.2%) patients had been further escalated to triple therapy and 5 (10.2%) had died.

Conclusions

Patients with repaired PAH-CHD treated with macitentan in the UK are a highly symptomatic group with limited exercise tolerance. Macitentan was well-tolerated overall and led to a significant improvement in objective exercise capacity.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship.
The role of cellular senescence in aortic dissection
Authors: Nakao E , Aoki H , Majima R , Hashimoto Y , Shibata R , Hayashi M , Ohno-Urabe S , Furusho A , Nishida N , Hirakata S , Fukumoto Y
Published: October 2022

Background

Aortic dissection (AD) is a catastrophic disease that occurs suddenly. The acute mortality is high and those who survived frequently suffer from serious complications such as aneurysm formation and distal ischemia due to progressive destruction of the aortic walls. Currently, no predictor of AD onset is available nor therapeutic intervention to specifically prevent the progressive destruction in AD, because the molecular pathogenesis is largely unknown. Clinical and experimental studies highlighted the importance of inflammation in AD, although the regulatory mechanism of inflammation remains unclear. Recently, we found that cell proliferation precedes the inflammatory response in AD. Because cell proliferation causes cellular senescence that can induce inflammatory response, we hypothesized that cellular senescence participates in AD pathogenesis.

Objective

We investigated if cellular senescence contributes to AD development and progression in mouse AD model.

Methods and results

A mouse AD model was created by continuous infusion of beta-aminopropionitrile and angiotensin II (BAPN+AngII), where AD starts to develop in 3 days and occurs to most of the mice in 14 days accompanied by frequent AD rupture and death. Infusion of BAPN+AngII resulted in the induction of senescence markers Ink4a from day 3 before AD onset and persisted for the 14 days of the observational period.

Cellular senescence, as demonstrated by the expression of senescence-associated beta-galactosidase, was evident in intimal endothelial cells, medial smooth muscle cells, adventitial macrophages and fibroblasts. We examined the role of cellular senescence in AD pathogenesis by oral administration of ABT263 which is known as “senolytics” that eliminates senescent cells. ABT263 treatment reduced the expression of the senescence marker, prevented the death by AD rupture, and ameliorated the severity of AD lesion compared to the vehicle treatment. Transcriptome analysis revealed that ABT treatment suppressed the immune and inflammatory response in AD. Quantitative RT-PCR confirmed that ABT treatment prevented the induction of p21Cip1, interleukin-6, several chemokines and their receptors by 3-day infusion of BAPN+AngII.

Conclusions

These findings demonstrated that senescence of multiple cell types precedes AD development, which is likely to induce the inflammatory response. Elimination of senescent cells effectively prevented AD progression and death. Therefore, cellular senescence represents a potential predictor and a therapeutic target for AD.

Funding Acknowledgement

Type of funding sources: None.
Structural, molecular and functional characterization of the aorta in HCM
Authors: Ibrahim A M , Roshdy M , Latif N , Sarathchandra P , Hosny M , Haikal S , Desouky A , Elsawy A , Elmozy W , Elaithy A , Khedr H , Afifi A , Aguib Y , Yacoub M
Published: October 2022

Introduction

Changes in the Extracellular Matrix (ECM) in Hypertrophic Cardiomyopathy (HCM) is thought to involve the myocardium as well as extracardiac tissues. The extent and significance of extra-myocardial changes has not been adequately studied.

Purpose

To describe the structural, molecular, and functional changes in the aorta of HOCM patients.

Methods

The structural and molecular changes in the aortic wall were studied in a cohort of 102 consecutive patients with hypertrophic obstructive cardiomyopathy undergoing myectomy. The biopsies were examined histologically, immunohistochemically and by Electron microscopy. The findings were compared to 10 normal controls obtained from the homograft bank of the Harefield hospital, following IRB guidelines. Changes in expression were quantified using morphometry and western blotting. For aortic stiffness, pulse wave velocity [PWV] was measured using Cardiac Magnetic Resonance (CMR), in the 102 HCM patients as well as age-matched 166 normal controls.

Results

Specimens from HCM aortas showed a misalignment in collagen and elastin fibres. There was a significant reduction in smooth muscle cells [SMCs] markers; integrin beta1 and smooth muscle actin, and an increase in an apoptosis marker, Caspase3. In addition, there was a significant decrease in the number of lamellae and an increase in the interlamellar distance in HCM aortas. FBLNs 1, 2 and 5 showed a reduction in expression in tunica intima and tunica media of HCM biopsies. PWV was significantly higher in HCM patients compared to healthy controls with the highest levels in patients with LV fibrosis.

Conclusion

This study illustrates the link between functional abnormalities in the aorta of HCM patients with structural and molecular changes. These findings can have a potential value in risk stratification and identify new therapeutic targets in HCM.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): STDF-EgyptMagdi Yacoub Foundation
Use of coronary calcium score to refine the cardiovascular risk classification of the new SCORE2 and SCORE2-OP algorithms in patients undergoing coronary CT angiography
Authors: Paiva M , Gomes D , Freitas P , Presume P , Santos R , Lopes P , Matos D , Guerreiro S , Abecasis J , Santos A , Saraiva C , Mendes M , Ferreira A
Published: October 2022

Introduction

Recently, the European Society of Cardiology issued new algorithms (SCORE-2 and SCORE2-OP) to estimate the 10-year risk of atherosclerotic cardiovascular disease (ASCVD). CACS has been shown to reclassify a significant proportion of patients when applied on top of several scores, but data on its use with these new algorithms are lacking.

The aim of this study was to assess the risk reassignment that can be attained by using CACS as a risk modifier of the SCORE-2 / SCORE2-OP classification, in patients referred for coronary CT angiography (CCTA).

Methods

Individuals without diabetes or known ASCVD were included in a single center registry of patients undergoing CCTA for suspected coronary artery disease (CAD). The 10-year risk of cardiovascular disease was calculated for each patient using SCORE-2 (ages 40–69) or SCORE2-OP (ages 70–89), and categorised as low-to-moderate, high, or very-high risk, according to guideline-recommended age-specific thresholds. CACS was considered to reclassify risk one level downward if = 0 in high or very-high risk patients, and reclassify risk upward if >100 (or >75th percentile) in those with low-to-moderate risk, or >1000 in those with high-risk.

Results

A total of 529 patients (43% men, mean age 63±10 years) were included, of which 13% (n=69) were active smokers. The mean systolic blood pressure and non-HDL-C values were 137±18 mmHg and 140±37 mg/dL, respectively.

A total of 47 patients (9%) had obstructive CAD on CCTA, classifying them as very-high risk. In the remainder 482 patients without obstructive CAD, the median CACS was 8 (IQR 0–80 AU), with 194 patients (40%) having CACS = 0, and 111 (23%) presenting CACS values ≥100.

The proportion of patients classified as low-to-moderate risk, high risk, and very high risk was 36%, 46% and 19% using the SCORE-2 / SCORE2-OP algorithm.

Using CACS would reclassify 150 patients (31%): 107 patients (22%) downward, and 43 patients (9%) upward. The extent of risk reclassification conveyed by CACS was 33% in patients assessed with SCORE-2, and 25% with SCORE-2 OP (p=0.082). Overall, most of the risk reassignment (42%, n=93) would occur in patients originally classified as high-risk – Fig. 1.

At the time of testing, 32% (n=61) of patients with CACS = 0 were being treated with statins, whereas 52% (n=58) of those with CACS ≥100 were not.

Conclusion

Even when the most recent SCORE-2 / SCORE-2 OP algorithms are used, risk refinement with CACS leads to the reclassification of nearly one third of the patients undergoing CCTA, mostly from downgrading risk. This opportunistic use of CACS may be employed to improve the allocation of primary prevention therapies.

Funding Acknowledgement

Type of funding sources: None.
The wrapping technique as an alternative method for the treatment of ascending aortic dilatation
Authors: Chlorogiannis D D , Synetos A , Doulamis I , Chatzigeorgiou G , Karabinos I , Mastrokostopoulos A , Panagopoulos Z , Toutouzas K , Chlorogiannis I
Published: October 2022

Background

The natural history of Ascending Aorta Dilatations (AAD) is unpredictable because acute dissections and ruptures have been observed even at aortic diameter sizes as small as 40s mm. Current data are unclear in terms of the simultaneous treatment of Ascending Aorta Aneurysms (AAD) with a coexisting surgical pathology requiring open heart surgery (OHS). To overcome the aforementioned complications in patients with ADD and a concomitant indication for OHS, we have applied a less invasive technique, in contrast to the conventional method of replacement of the ascending aorta with a supracoronary synthetic tubular graft interposition.

Purpose

The safety and efficacy of the Wrapping Ascending Aorta Dilatation (WAAD) technique that is based on the wrapping of the dilated ascending aorta with a synthetic graft from the sinotubular junction to the origin of innominate artery.

Methods

We studied 254 patients who underwent ascending aorta surgery from 2000 to 2020 at a Euroclinic Hospital Greece, from the same senior Cardiac Surgeon. Patients with an AAD with a diameter of 40–45mm in combination with a coexisting cardiac surgical pathology requiring OHS were treated with the wrapping technique, while patients with AAD diameter more than 45mm were treated with replacement. The WAAD technique was applied during patient's rewarming period using a longitudinally opened synthetic tubular Dacron graft around the AAD, without increasing the patient's time on extracorporeal circulation. The mean follow-up interval was 12.2±4.5 years.

Results

Two hundred and three patients (80%) were treated with OHS with replacement of the ascending aorta. Fifty one patients (20%) had an AAD with a diameter of 40–45mm (mean diameter 43±3.3mm) in combination with a coexisting cardiac surgical pathology requiring OHS and were treated with the WAAD technique. due to concomitant aortic valve surgery in 34 patients (67%), coronary artery bypass Graft in 10 patients (19.6%) and mitral valve surgery in 7 (14%). One of the patients who underwent mitral valve surgery exhibited AAD as well as dilation of the common pulmonary trunk extending to the right pulmonary artery and had both treated with the wrapping technique. During follow up no AAD recurrence or any other event concerning the ascending aorta or pulmonary artery were observed.

Conclusion

In patients with AAD undergoing OHS for a different cardiac pathology, WAAD is safe and effective and may be beneficial for patients with AAD with an aortic diameter of 40–45mm. Further randomized control studies are needed to confirm our results.

Funding Acknowledgement

Type of funding sources: None.
Aortic and vascular involvement in Loeys-Dietz Syndrome. Results from the REPAG registry (Spanish network of genetic aortic diseases)
Authors: Teixido Tura G , Martinez D , Calvo F , Garcia-Orta R , Sanchez R , Larranaga J M , Hernandiz A , Diaz E , Montanes E , Cabrera F , Sabate A , Nistal F , Forteza A , Evangelista A
Published: October 2022

Background

LDS is a rare disease due to genetic variants in the TGFB pathway. Limited information is available regarding the overall aortic and vascular outcome of these patients

Purpose

To evaluate aortic and vascular complications of patients with mutations in the TGFB pathway.

Methods

Retrospective longitudinal study including patients with (likely) pathogenic (LP/P) variants in the TGFbeta pathway from 10 tertiary centers. Clinical and imaging data were reviewed and data on aortic and vascular outcome included.

Results

A total of 163 patients were included (47.9% women, 38.6% index cases), mean age at first evaluation 32.3±20.4 years, 27.0% with age <16 years. 70 TGFBR1, 43 TGFBR2, 29 SMAD3, 9 TGFB2 and 12 TGFB3 (Table1)

During a mean follow-up of 4.7±3.7 years, 54 (33.1%) patients had at least 1 aortic surgery (max 6). Mean age at first aortic surgery was 37.2±16.8 years (Range 1.2–72.9). First surgery was elective in 42 (77.8%), and included aortic root or ascending aorta in 40 (95.2%) and isolated descending aorta in 2 (4.8%). Emergent surgery included aortic root or ascending aorta in 11 (92.7%). Ascending aorta-root diameter previous to elective surgery was 48.9±4.9mm (range 41–65). 7 patients died during follow-up (2 intracranial bleeding, 1 SD, 2 aortic ruptures, 1post aortic surgery, 1 non-CV). Furthermore, 19 acute aortic syndromes (AAS) were reported (17 dissections, 2 haematomas) in 18 patients, 10 type A (52.6%). Mean age at first AAS was 42.3±11.1 years (min 19.7 years to 62.9 years)

Median survival free of intervention, dissection or death was 57.1 years, being worst for men than women (44.7 yrs vs 69.1 years, p<0.001) (Figure 1), these gender-difference only remained significant in the TGFBR1 and SMAD3 groups (p=0.005 and p=0.008) Regarding aortic branch and intracranial aneurysms, a total of 383 imaging studies of aortic branches and 223 cranial imaging studies were performed during the clinical follow-up. 21 cranial aneurysms and 73 aortic branch aneurisms were reported. 14 (11.5%) patients suffered 19 aneurysms-related events (3 dissections, 3 ruptures, 13 interventions).

Conclusions

In patients with Loeys-Dietz Syndrome, there's a high prevalence of aortic surgeries and acute aortic events, with high numbers of peripheral and intracranial aneurysms. A worst prognosis in men than in women is observed in TGFBR1 and SMAD3 variants. Thus, specialized clinical and imaging follow-up is crucial in the management of these patients

Funding Acknowledgement

Type of funding sources: None.
Male-female differences in acute type B aortic dissection: the DisSEXion study
Authors: Meccanici F , Thijssen C G E , Gokalp A L , De Bruin J L , Bekkers J A , Van Kimmenade R R J , Geuzebroek G S C , Poyck P , Ter Woorst F J , Post M C , Heijmen R H , Mokhles M M , Takkenberg J J M , Roos-Hesselink J W , Verhagen H J M
Published: October 2022

Background/Introduction

Acute type B aortic dissection (ATBAD) is a cardiovascular emergency with high risk of morbidity and mortality. Elucidating male-female differences in ATBAD might help optimize patient-specific care, while data is scarce on this topic.

Purpose

The aim of this study was to identify differences between male and female ATBAD patients in presentation, management and outcomes.

Methods

A retrospective cohort study was conducted including all consecutive patients who presented with ATBAD between 2007–2017 in four tertiary centers. Non-acute, traumatic, and iatrogenic dissections were excluded. We included patients presenting with an intramural hematoma or penetrating aortic ulcer in acute setting.

Results

The study population consisted of 384 patients, of which 41% (n=156) was female. In comparison to males, females presented at an older age (67 [IQR: 57–73] vs. 62 [IQR: 52–71], p=0.015) and fewer female patients had a history of abdominal aortic aneurysm (6% vs. 15%, p=0.009). Imaging diagnostics revealed a smaller proportion of patients with distally extended dissections in females. DeBakey type IIIb was diagnosed less frequently in females (73% vs. 85%, p=0.008) as was renal artery involvement (48% vs. 66%, p=0.009). Furthermore, classical type B dissection was less often observed in female patients compared to male patients (56% vs. 78%, p<0.001). Absolute maximum thoracic aortic diameters were not significantly different in females and males (44.0 [38.0–50.0] mm vs. 42.0 [39.0–49.0], p=0.870). No male-female differences were found in treatment strategy (p=0.561, Figure 1). In-hospital/30-day mortality was 9.6% in female patients and 11.8% in male patients (p=0.603). Long-term mortality did not show a significant male-female difference (p=0.90) during a median follow-up duration of 6.1 [IQR: 4.1–9.1] years (Figure 2).

Conclusion

This study showed that female patients were older at presentation, while male patients more often had distally extended dissections. Although mortality was not significantly different, we encourage male-female specific risk factor studies on late mortality. In this way ATBAD male and female patients at high risk of mortality can be identified and patient-specific care can be implemented.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): ZonMw
The safety and efficacy of a modified Wrapping technique for the treatment of ascending aortic dilatation
Authors: Chlorogiannis D D , Synetos A , Doulamis I , Chatzigeorgiou G , Karabinos I , Mastrokostopoulos A , Panagopoulos Z , Toutouzas K , Chlorogiannis I
Published: October 2022

Background

Current data are unclear in terms of the simultaneous treatment of Ascending Aorta Aneurysms (AAD) with a coexisting surgical pathology requiring open heart surgery (OHS), since replacement of the ascending aorta in all of those AAD patients may increase morbidity and mortality in respect with longer time in extracorporeal circulation. To overcome the aforementioned complications in patients with ADD and a concomitant indication for OHS, we have applied a less invasive technique, in contrast to the conventional method of replacement of the ascending aorta with a supracoronary synthetic tubular graft interposition

Purpose

We tested the safety and the efficacy of the Wrapping Ascending Aorta Dilatation (WAAD) technique that is based on the wrapping of the dilated ascending aorta with a synthetic graft from the sinotubular junction to the origin of innominate artery.

Methods

We retrospectively studied 254 patients who underwent ascending aorta surgery from 2000 to 2020 at Euroclinic Hospital of Athens Greece, from the same senior Cardiac Surgeon. Patients with an AAD with a diameter of 40–45mm in combination with a coexisting cardiac surgical pathology requiring OHS were treated with the wrapping technique, while patients with AAD diameter more than 45mm were treated with replacement. The WAAD technique was applied during patient's rewarming period using a longitudinally opened synthetic tubular Dacron graft around the AAD, without increasing the patient's time on extracorporeal circulation. The mean follow-up interval was 12.2±4.5 years.

Results

Two hundred and three patients (80%) were treated with OHS with replacement of the ascending aorta. Fifty one patients (20%) had an AAD with a diameter of 40–45mm (mean diameter 43±3.3mm) in combination with a coexisting cardiac surgical pathology requiring OHS and were treated with the WAAD technique. due to concomitant aortic valve surgery in 34 patients (67%), coronary artery bypass Graft in 10 patients (19.6%) and mitral valve surgery in 7 (14%). One of the patients who underwent mitral valve surgery exhibited AAD as well as dilation of the common pulmonary trunk extending to the right pulmonary artery and had both treated with the wrapping technique. During follow up no AAD recurrence or any other event concerning the ascending aorta or pulmonary artery were observed.

Conclusion

In patients with AAD undergoing OHS for a different cardiac pathology, WAAD is safe and effective and may be beneficial for patients with AAD with an aortic diameter of 40–45mm. Further randomized control studies are needed to confirm our results.

Funding Acknowledgement

Type of funding sources: None.
Diversity in the characteristics of spontaneous ruptured aortic plaques
Authors: Komatsu S , Takahashi S , Yutani C , Iwa N , Takewa M , Noda H , Ohara T , Kodama K
Published: October 2022

Background

Spontaneous ruptured aortic plaques (SRAPs) act as emboli for systemic organs because SRAPs might contain CCs which cause inflammation besides mechanical obstruction. The purpose of the study is to clarify the difference of the characteristics of representative SRAPs, puff rupture and puff-chandelier rupture sampled by non-obstructive general angioscopy. (NOGA)

Methods

A total of 177 puff-chandelier ruptures which blown out spontaneously and glittered against the light of the angioscopic fiber and 105 puff ruptures which did not glitter were sampled by NOGA in patients having or suspected coronary artery disease. Sampled plaques were analyzed two kinds of methods, conventional Hematoxylin-eosin stain and methods without solvents. Samples were diagnosed if the component of atheroma was detected with either method. The percentage of content of CCs, the number of CCs, the longer and shorter diameters were compared between blood sampled from puff and puff-chandelier rupture.

Results

Samples were diagnosed as atheroma 56% of puff-chandelier rupture and 27% of puff- rupture. (p<0.0001) Higher number of CCs was included in puff-chandelier rupture than in puff-rupture. (12,955 [3,977, 25,795] vs. 3,182 [909, 7,273]) The longer and shorter diameters of plaque components of puff rupture were smaller than those of puff-chandelier rupture. (p=0.0259 and p=0.0286, respectively.) CCs were tended to be included puff-chandelier rupture than puff-rupture. (53% vs. 16%, respectively; p<0.0001) Visible debris was obtained only 13% of puff rupture and 26% of puff-chandelier rupture.

Conclusions

Diversity of SRAPs were shown as that puff rupture had less CCs and more fibrin than puff-chandelier rupture, suggesting that potentially less inflammation and more fibrinolytic.

Funding Acknowledgement

Type of funding sources: None.
Electronic hookah vaping reduces plasma concentrations of nitrate/nitrite and increases systemic oxidative stress
Authors: Rezk-Hanna M , Cheng C W , Adolfo A , Brecht M L
Published: October 2022

Background

Electronic (e-) hookah–a new category of vaping devices–has increased in use among young adults in recent years. E-hookahs utilize the placement of e-bowls on traditional water pipes, allowing the flavored aerosol to pass through a water-filled base before being inhaled. Though advertised as a safe tobacco alternative, e-hookahs deliver flavored nicotine by creating an aerosol of fine particles and other free radicals that may increase cardiovascular disease risk. While acute e-hookah vaping impairs endothelial function, the underlying mechanism is not completely understood.

Purpose

To determine the mechanistic involvement of nitric oxide (NO) and oxidative stress underlying the acute e-hookah induced endothelial dysfunction.

Methods

Healthy young adult chronic hookah smokers (n=7; 26±1 years of age, 24.4±0.8 kg-m2; mean ±SE) were randomized to vape two 30-minute sessions of flavored e-hookah and sham vaping, separated by a 7-day washout period. Flow-mediated dilation (FMD) of the brachial artery was performed with the use of ultrasound. Circulating plasma nitrite/nitrate (NOx), as an index of nitric oxide (NO) concentration, and lipid peroxidation marker 8-isoprostane concentrations, as well as smoking exposure biomarkers (plasma nicotine and exhaled carbon monoxide) were measured before and after the vaping sessions.

Results

As compared to unchanged parameters with sham vaping (p=ns), e-hookah vaping induced an acute reduction in FMD by −27±3% (pre- vs. post-vaping, p<0.001), suggesting impairment in endothelial function. These vascular changes were accompanied by significant reductions in circulating plasma levels of NOx and increases in 8-iso prostaglandin F2a levels (−41±11% and +28±11%, respectively; p<0.001). Plasma nicotine concentrations increased 4-fold more after vaping e-hookah, whereas exhaled CO levels did not change (p=ns).

Conclusions

Our data demonstrate that e-hookah vaping transiently increases systemic oxidative stress and decreases NOx levels, the latter implies reduced NO bioavailability and is in line with the observed impairment in endothelial function, expressed by acute FMD reductions. Thus, in contrast to the unsubstantiated beliefs that e-hookah vaping is benign, in overtly healthy young adults, e-hookah vaping causes acute vascular functional impairment, likely mediated by oxidative stress.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): University of California Tobacco-Related Disease Research Program, University of California
Coronary artery stenosis and vulnerable plaque quantification on CCTA by deep learning methods
Authors: Sehly A , He A , Jaltotage B , Lan N S R , Joyner J , Flack J , Sokolov J , Chronos N , Ko B , Chow B , Dwivedi G , Ihdayhid A R
Published: October 2022

Introduction

Coronary computed tomography angiography (CCTA) has emerged as a reliable non-invasive modality to assess coronary artery stenosis (CAS) severity and vulnerable plaque (VP). However, comprehensive CCTA assessment, especially VP, is time-consuming and dependent on reader expertise, limiting CCTA's true potential.

Purpose

In this study, we aim to develop and validate a deep learning (DL) based system capable of evaluating CAS severity and characterising VP on CCTA.

Methods

A DL system was trained to assess CAS severity on 3909 expert annotated vessels. A subset of 824 vessels was used to train the model to assess for the presence of VP. The model was based on a 2D U-Net and 3D convolutional neural network architecture. The system automatically performed vessel tracking and segmentation to quantify stenosis severity and characterise the presence of VP. CAS severity was categorised as 0%, 1–49% and ≥50%. VP was defined as: low attenuation plaque (LAP; ≤30 Hounsfield units), positive remodelling (PR; ≥10% diameter) and spotty calcification (SC; <3mm). The model was then tested on 1435 vessels for CAS (mean calcium score 197±502) and a subset of 365 vessels for VP (mean calcium score 419±551), and its diagnostic performance compared with expert readers.

Results

The CAS testing data had a prevalence of 75% (1080/1435), 18% (257/1435) and 6.8% (98/1435) for 0%, 1–49% and ≥50% stenosis, respectively. VP was present in 20% (72/365) in the respective dataset with 44% (32/72) LAP, 19% (14/72) PR and 36% (26/72) SC. Average analysis time for CAS severity and VP was 3.7±2.0s and 3.5±1.8s, respectively. Diagnostic performance of our system is summarised in Tables 1 (CAS severity) and 2 (VP characteristics).

Conclusions

We developed an DL based system capable of rapidly evaluating CAS severity and characterising VP on CCTA. Our system demonstrated high specificity and accuracy for both CAS severity and VP quantification when compared with expert readers.

Funding Acknowledgement

Type of funding sources: None.
Evaluation of Takayasu's arteritis activity by ultrasound localization microscopy
Authors: Goudot G , Jimenez A , Mohamedi N , Sitruk J , Khider L , Mortelette H , Tanter M , Messas E , Pernot M , Mirault T
Published: October 2022

Objectives

Use of sulphur hexafluoride microbubbles (MB) with ultrasound can provide arterial wall enhancement. The use of ultrafast imaging with MB super-localization offers the possibility of ultrasound localization microscopy (ULM) and thus a visualization of in vivo carotid vasa vasorum. We aim to perform in vivo Vasa vasorum imaging in the carotid wall in Takayasu's arteritis and to provide a correlation with the disease's activity.

Methods

Patients with Takayasu arteritis were consecutively included in the national referral centre. Assessment of activity was performed by NIH activity index, with measurement of biological inflammation, morphological evaluation by computed tomography (CT) angiography, and 18-fluorodeoxyglucose CT scan. Ultrafast ultrasound imaging was performed with a 7 MHz central frequency linear probe. A dedicated contrast imaging sequence (plane waves with 8 angles, frame rate 500 Hz, voltage 8 V, duration of 8 s), coupled with the intravenous injection of sulphur hexafluoride MB allow us to store the raw radio frequency data of the MB passage. After a pre-processing step to accumulate frames properly including a frames selection and a movement correction, the MB were localized then tracked, allowing reconstruction of the vasa vasorum. The inflammation was quantified through MB tracked and normalized for inter acquisition comparison.

Results

16 patients were included. 5 patients (median age 35.8 [24.5–46.0] years, 3 women) had active disease and 11 patients (37.2 [31.7–47.3] years, 9 women) had quiescent disease. The passage of MB allowed the visualisation of microvessels within the arterial wall for active cases. The number of MB detected per second in the wall was 118 [80–169] for active cases vs. 13 [10–15] for quiescent cases (p=0.0005).

Conclusion

ULM allows visualization of microvessels within the carotid wall, with significantly greater MB passage in active Takayasu arteritis. ULM provides for the first time a precise visualization in vivo of the vasa vasorum and gives access to quantification of the vascularity of the arterial wall.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Société française de cardiologie
Persistent medication adherence and lifestyle changes compliance in patients with type 2 diabetes undergoing minor foot amputation and one-year all-cause mortality
Authors: Shalaeva E , Bano A , Kasimov U , Janabaev B , Azizova F , Baumgartner I , Laimer M , Saner H
Published: October 2022

Background

The 3-years mortality rate in patients with Type 2 diabetes (T2D) after minor amputations may reach 53–80%. The aim of the study was to evaluate the impact of persistent medication adherence and compliance with lifestyle recommendations on 1-year all-cause mortality in patients with T2D and peripheral artery disease (PAD) after minor foot amputation.

Methods

This is a prospective, single-center, observational cohort study including 785 consecutive T2D patients with PAD undergoing minor amputations and followed-up over 1 year (mean age 62.3±7.2 years; 62.8% males). Based on adherence and compliance, patients were divided into 4 groups: adherent/compliant (n=432), adherent/non-compliant (n=101), compliant/non-adherent (n=68), non-adherent/non-compliant (n=184). Secondary prevention recommendations included healthy diet, smoking cessation, physical exercise ≥30 min/day and >80% drug intake (wound healing, antidiabetic, cardiovascular treatment, dual antiplatelet and statin treatment). Cox proportional hazard models were used to examine how variables predict one-year all-cause mortality.

Results

One-year all-cause mortality was 16.9% (n=133) at 1-year follow-up (Figure 1). After adjusting for confounders, compared to adherent/compliant patients, all other groups had an increased risk of one-year mortality. In non-adherent/non-compliant patients HR=9.08 [95% CI 5.55, 14.86], p<0.001; in adherent/non-compliant patients HR=3.86 (95% CI [2.08, 7.14], p<0.001), in non-adherent/compliant patients HR=2.98 (95% CI [1.45, 6.08] p=0.003). After adjustment, age, history of myocardial infarction, foot infection also remained significant (Figure 2).

Conclusion

T2D and PAD patients who were persistently medication non-adherent and non-compliant to lifestyle changes recommendations had a nine-fold increased risk for one-year all-cause mortality after PFA, non-compliance only increased mortality 3.8-fold, and non-adherence only – 3.0-fold, which outline the importance of secondary preventive measures.

Funding Acknowledgement

Type of funding sources: None.
The effect of smoking on exhaled carbon monoxide and arterial elasticity during prolonged surgical mask use in the COVID-19 era
Authors: Ikonomidis I , Katogiannis K , Kourea K , Kostelli G , Tsilivarakis D , Pavlidis G , Thymis J , Michalopoulou E , Prentza V , Lambadiari V , Kouretas D , Biondi-Zoccai G
Published: October 2022

Aims

During the COVID-19 era, the use of surgical face mask hampers the spread of COVID infection. The impact of smoking while wearing a surgical face mask on exhaled CO and vascular function in smokers has not been investigated.

Methods

We studied 40 smokers of conventional cigarettes (ConCig), 40 exclusive heat-non-burn cigarettes (HNBC) users and 40 non-smokers with similar age and sex (p>0.05 [45.1±10.8 years, 34 (28.3%) male]. We measured exhaled CO (parts per million [ppm]), pulse wave velocity (PWV) and central systolic blood pressure (cSBP).

Results

A significant interaction was found between CO at baseline and at the end of an 8h period with and without wearing a mask and the use of tobacco products vs no-smoking (F=46.58, p for interaction<0.001). Exhaled CO was higher in ConCig smokers compared to HNBC and nonsmokers throughout the study (p<0.05).

Compared to baseline, the percent increase of CO was greater after smoking ConCig with than without wearing a mask for 8h (141.79% [95% confidence interval (CI): 116.16–167.42] vs 56.99% [95% CI: 44.80–69.18], p<0.001). Similarly, the percent increase of CO was greater after smoking HNBC with than without wearing a mask for 8h (103.84% [95% CI: 70.50–137.18] vs 30.76% [95% CI: 15.61–45.92], p<0.001). Among non-smokers, the use of mask did not alter exhaled CO (p>0.05).

In both ConCig and HNBC users, all vascular markers were increased at the end of each one of two study assessments, compared to baseline (p<0.05). In non-smokers, the use of a mask had a neutral effect on vascular markers (p>0.05).

Compared to baseline, the percent increase of PWV was greater after smoking ConCig with than without wearing a mask for 8h (16.54% [95% CI: 9.13–23.95] vs 4.36% [95% CI: 1.41–7.31], p=0.001).

Compared to baseline, the percent increase of PWV was greater after smoking HNBC with than without wearing a mask for 8h (9.71% [95% CI: 4.57–14.84] vs 2.73% [95% CI: 0.12–5.35], p=0.003).

Conclusion

Ssmoking of any tobacco product (conventional tobacco or HNBC) during a prolonged use of a surgical face mask may further compromise vascular function. Thus, quitting both conventional and HNBC cigarettes is imperative for a better health in the COVID-19 pandemic.

Funding Acknowledgement

Type of funding sources: None.
Optimal strategy for antiplatelet therapy after endovascular revascularization in patients with lower extremity artery disease
Authors: Kim G S , Seo J K , Kim B G , Byun Y S , Kim B O
Published: October 2022

Background

The duration of antiplatelet therapy after endovascular revascularization in patients with lower extremity artery disease (LEAD) has not been well established. This study aimed to evaluate the clinical outcome according to the duration of dual antiplatelet therapy (DAPT) in real practice.

Methods

From April 2009 to June 2019, 376 patients with LEAD underwent successful endovascular revascularization. After the procedure, the received single antiplatelet therapy (SAPT) or DAPT of various durations were classified into two groups (SAPT or DAPT <6 months vs. DAPT ≥6 months). The primary outcomes were major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs). The safety outcome was moderate-to-severe bleeding according to the Global Use of Strategies to Open Occluded Arteries (GUSTO) criteria.

Results

Over the 40-month follow-up period, MACE occurred less frequently in the DAPT ≥6 months group than that in the SAPT or DAPT <6 months group (12.4% vs. 23.8%; hazard ratio [HR]: 0.56; 95% confidence interval [CI]: 0.35–0.89; p=0.014) after inverse probability-weighted adjustment and propensity-score matching analysis (HR: 0.55, 95% CI; 0.30–0.99, p=0.048). The incidence of MALE did not show significant difference between the two groups (DAPT ≥6 months group: 17.1% vs. SAPT or DAPT <6 months group: 13.1%; HR: 1.05; 95% CI: 0.62–1.78; p=0.846). A significant difference between the DAPT ≥6 months group and the SAPT or DAPT <6 months group was not observed regarding the incidence of moderate-to-severe GUSTO bleeding.

Conclusions

In patients with LEAD, DAPT for ≥6 months after endovascular revascularization was associated with a lower incidence of MACE.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): National Research Foundation of Korea (NRF) grant funded by the government of Korea (MSIT) (No. 2019R1G1A1100442).
Influence of concomitant percutaneous transluminal angioplasty with percutaneous coronary intervention on outcomes in patients with stable lower extremity artery disease
Authors: Lee Y , Shin J H , Kim B S , Kim W H , Kook H , Park H C
Published: October 2022

Background

Patients with stable lower extremity artery diseases (LEAD) frequently present with coronary artery diseases; thus, concomitant percutaneous transluminal angioplasty (PTA) at the time of percutaneous coronary intervention (PCI) is often performed. We investigated the influence of concomitant PTA on both cardiovascular (CV) and limb outcomes in the Korean National Health Insurance Service registry.

Methods

Among 78,185 patients undergoing PCI between 2012 and 2015, 6,563 patients (279 for the PTA+PCI group vs. 6,284 for the PCI group) suffering from stable LEAD without limb ischemia were included. Major adverse CV events (MACEs) were defined as a composite of CV death, myocardial infarction (MI) and coronary revascularization. Patients were followed for at least 3 years.

Results

After 1:5 propensity score matching was conducted, 279 patients in the PTA+PCI group and 1,385 patients in the PCI group were compared. The risk of all-cause death was higher in the PTA+PCI group than in the PCI group, whereas the risks of MACE, MI, revascularization, stroke, CV death and bleeding event were not different between the 2 groups in the matched cohort. In contrast, the risks of end-stage renal diseases and unfavorable limb outcomes were higher in the PTA+PCI group than in the PCI group (Figure 1). Mediation analyses revealed that amputation and repeat Percutaneous transluminal angioplasty after discharge significantly mediated the association between the concomitant PTA and all-cause death (Figure 2).

Conclusions

CPTA at the time of PCI is not associated with an increased risk of CV events but may increase the risk of all-cause death by increasing unfavorable renal and limb outcomes in patients with stable LEAD.

Funding Acknowledgement

Type of funding sources: None.
Pulmonary arterial angioplasty in peripheral pulmonary arterial stenosis in RNF213 vasculopathy: effective but high-risk treatment with reperfusion injury
Authors: Kwon W , Chang S A , Jeon K , Bak M , Park T K , Yang J H , Kim D K
Published: October 2022

Background

p.Arg4810Lys variant of the ring finger protein 213 (RNF213) vasculopathy is a nonsyndromatic vasculopathy involving multisystemic organs including pulmonary arteries. Peripheral pulmonary arterial stenosis (PPAS) with diffuse stenosis and beaded appearance is a unique feature of this disease and no treatment option has been tried before.

Methods

We performed BPA for PPAS in RNF213 patients (n=7). Severity of pulmonary hypertension was assessed by echocardiography and right heart catheterization at the baseline. Several clinical and hemodynamic parameters were followed up after each BPA sessions.

Results

All of the patients had dyspnea on exertion. Right ventricular dysfunction was observed in six patients and NT-proBNP was elevated (949.2±1148.1 pg/mL). Baseline echocardiography showed severe pulmonary hypertension (70.1±19.2 mmHg). Pulmonary arterial ballooning was performed to all patients, but stenting (n=6) and cutting balloon (n=1) was necessary due to elastic recoil. Improvement of clinical and hemodynamic parameters was achieved in six patients after 5.3 sessions of BPA in average. Reperfusion edema was seen in four patients, eventually leading to death in one patient.

Conclusions

Pulmonary arterial angioplasty, when coupled with stenting, is an effective treatment for PPAS with RNF213 vasculopathy. Although reperfusion injury was common and fatal in a few cases, it is the only modality to improve the patient's symptom and hemodynamics till now. Careful selection of the target population should be preceded to perform the intervention.

Funding Acknowledgement

Type of funding sources: None.
Smoking promotes vascular damage in apparently healthy men with low testosterone and increased subclinical inflammation
Authors: Ioakeimidis N , Dima I , Terentes-Printzios D , Xydis P , Angelis A , Solomou E , Gardikioti V , Gourgouli I , Papadatos S , Kalfountzos D , Tsioufis C , Vlachopoulos C
Published: October 2022

Background

Testosterone deficiency and increased inflammation are both associated with an unfavourable vascular profile. Aim of the study was to examine whether smoking significantly deteriorates the effect of these pathophysiological mechanisms on arterial wall properties.

Methods

Carotid intima media thickness (cIMT) and aortic pulse wave velocity (aPWV) were measured in 87 smokers and 112 aged-matched never smokers (mean age: 49±5 yrs) with no other cardiovascular (CV) risk factors/or manifest CV/atherosclerotic disease. Plasma total testosterone (TT) and high sensitivity reactive protein (hsCRP) levels were measured in the whole study population.

Results

Both smokers and never smokers were divided into four subgroups according to measured low or normal TT levels (low TT<3.5 ng/ml) and high or low hsCRP levels. BMI and LDL-C levels were not different between the subgroups. In smokers the four TT/CRP subgroups had comparable cumulative tobacco smoke exposure. In smokers the low TT/high CRP subgroup had significantly higher aPWV and cIMT compared to the three other subgroups (P<0.01 and P<0.05, respectively by ANOVA, figures A-B) while in never smokers the four TT/CRP subgroups had comparable aPWV and cIMT (all P>0.05, figures C-D). The differences in aPWV and cIMT measurements between TT/CRP subgroups in smokers remained statistically significant after adjustment for age.

Conclusions

The study shows that low TT combined with high CRP are associated with increased carotid IMT and aortic PWV in smokers with no other CV risk factors, while in never smokers the effect of combined low TT and high CRP concentration was not significant. Considering the predictive value of aortic stiffness and carotid thickness, the finding of this study imply interrelationships between tobacco cigarette smoke, subclinical inflammation and low testosterone level regarding changes in arterial wall properties.

Funding Acknowledgement

Type of funding sources: None.
Enhanced neutrophil activity, but not neutrophil extracellular trap markers, is found in patients with symptomatic chronic peripheral arterial disease
Authors: Buso G , Faggin E , Bressan A , Galliazzo S , Cinetto F , Felice C , Fusaro M , Erdmann A , Pauletto P , Rattazzi M , Mazzolai L
Published: October 2022

Background/Introduction

Neutrophil degranulation and neutrophil extracellular traps (NETs) are suggested to play a role in cardiovascular (CV) disease development [1]. Human studies showed that markers of NETs, are increased in patients with severe coronary atherosclerosis and predict risk of cardiac events [2]. The role of NETs in peripheral artery disease (PAD) has not been investigated.

Purpose

To measure circulating markers of neutrophil activity in patients with symptomatic PAD compared with matched healthy controls, evaluate their association with disease severity, and assess their prognostic value.

Methods

Multicenter, prospective case-control study. Circulating levels of polymorphonuclear neutrophil (PMN)-elastase, neutrophil gelatinase-associated lipocalin (NGAL), myeloperoxidase (MPO), and NETs-associated MPO-DNA complexes were measured in patients with symptomatic PAD and heathy controls. The former underwent comprehensive vascular evaluation including ankle-brachial index (ABI) calculation, transcutaneous oximetry measurement, constant-load treadmill test, 6-minute walking test, pulse wave velocity, and flow-mediated dilatation of the brachial artery. Six-month outcomes were: occurrence of major adverse CV (MACE) and limb events (MALE), ABI reduction ≥0.15, and 6-minute walking distance reduction ≥20 m.

Results

Overall, 110 participants were included, 66 had symptomatic PAD. Levels of all but one biomarker (MPO-DNA) were significantly higher in patients with PAD compared with healthy controls (Fig. 1). No significant correlation was found between biomarkers and vascular tests in patients with PAD. Baseline PMN-elastase (adjusted hazard ratio [HR]: 1.010; 95% CI: 1.000–1.020; p=0.040) and MPO (adjusted HR: 1.027; 95% CI: 1.004–1.051; p=0.019) were predictive of MACE and/or MALE at 6-month follow-up in patients with symptomatic PAD (Table 1).

Conclusions

Present data show enhanced neutrophil activity, but not NETs levels, in patients with symptomatic PAD compared to controls. Baseline PMN-elastase and MPO levels were associated with worst CV outcome in patients with chronic PAD. These data suggest a role of neutrophils in PAD development and severity that needs to be further elucidated.

Funding Acknowledgement

Type of funding sources: None.