bluuebunny/crossref_metadata_2025_split huggingface dataset:
Behavior of right atrial strain in patients with advanced idiopathic pulmonary arterial hypertension after initiation of specific combined therapy
Authors: Samuel I , Locas J , Mostafa S , Khaled A , El Mozy W , Gergis M , Hassan A 
Published: October 2022

Abstract

Background
Right atrial (RA) function has emerged as an important determinant of outcome in pulmonary arterial hypertension (PAH). However, studies exploring RA function and assessing its behavior in response to specific PAH combination therapy, independent of RA size in patients with PAH is not adequately investigated.

Purpose
Assess the behavior of strain based measures of RA in response to combined PAH therapy, independent of RA size in patients with PAH.

Methods
RA peak longitudinal strain (PLS) and peak active contraction strain (PACS) were retrospectively assessed in 38 patients with advanced idiopathic pulmonary arterial hypertension (IPAH) who were referred to Aswan heart Centre and not receiving proper GDMT; at baseline and during follow-up after initiation of specific PAH combination therapy in the form of either Sildenafil/Bosentan or Sildenafil/Macitentan.

Results
Most of the patients were females with median (IR) age 34 (27–39) years. All patients presented with dyspnea WHO-FC III. At baseline, all patients were receiving only monotherapy in the form of sildenafil. Median (IR) time to echocardiographic follow-up was 11 (8–18) months. Patients presented with markedly right ventricle (RV) and RA enlargement, depressed RV systolic function, and reduced RA strain parameters compared with values previously reported in healthy controls. Among various baseline associations of the RA PLS, the strongest were with baseline RA area (rho: −0.659; p&lt;0.001) and RVEF by CMR (rho: 0.570; p&lt;0.001). At follow up; RA PLS and PACS significantly increased (16.6 vs 24 and 7.06 vs 11.42, respectively: p&lt;0.001); however, RA area did not show significant decrease. Only RV TDI & FAC showed significant improvement among different RV function parameters measured by echocardiography. During the follow up period, 11 out of 38 patients (28.9%) were hospitalized. RA PLS change was significantly lower in the hospitalized group than the non-hospitalized group (4.40 vs 10.2; p=0.014). RA PLS change was independently associated with hospitalization in the multivariate regression analysis (95% CI: −0.061 to −0.010; p=0.008).

Conclusion
Initiation of specific PAH combination therapy in undertreated patients with IPAH showed improvement in RA strain parameters despite no change in RA area during follow up.

Funding Acknowledgement
Type of funding sources: None.
Electroanatomic mapping and radiofrequency catheter ablation of atrial fibrillation or atrial tachycardia in patients with pulmonary hypertension. Ancillary analysis
Authors: Havranek S , Fingrova Z , Skala T , Reichenbach A , Dusik M , Ambroz D , Dytrych V , Jansa P , Klimes D , Wichterle D 
Published: October 2022

Abstract

Background
Atrial fibrillation (AF) and related atrial tachycardias (ATs) are common arrhythmias in patients with pulmonary hypertension (PH). They are currently assessed in a multicentre randomized trial investigating extensive radiofrequency catheter ablation of the arrhythmogenic substrate on top of selective ablation of clinical arrhythmia alone.

Purpose
Irrespective of the randomization scheme, we compared clinical and procedural characteristics in patients with AF versus those with right-sided ATs.

Methods
Out of 74 patients with combined post- and pre-capillary or isolated pre-capillary PH, two study subgroups were composed: AF group included 40 patients and AT group included 31 patients: 24 with typical atrial flutter (AFL) and 7 with other right-sided ATs (2 upper loop reentry ATs, 2 focal ATs from coronary sinus ostium, 1 focal AT from terminal crest, and 2 polymorphic ATs from high right atrium). Three patients with inducible AV nodal reentrant tachycardia were excluded from this analysis. Biatrial electroanatomic mapping was performed in all patients. The data are presented as medians (interquartile range) and compared by the Mann-Whitney U test.

Results
The clinical and procedural characteristics of AF and AT groups are shown in Table. Cycle length (CL) of both induced and spontaneous AFL was 302 (267; 324) ms. Non-CTI-dependent ATs had CL 425 (350; 480) ms. In patients with AF, the dominant CL was 183 (152; 221) and 191 (154; 210) ms in right and left atrial appendage, respectively. In the whole cohort, pulmonary vein isolation was done in 49 (66%), left atrial substrate ablated in 23 (31%), cavotricuspid isthmus block achieved in 46 (62%), superior vena cava isolation completed in 28 (39%), intercaval line ablated in 26 (36%), and right atrial substrate or focal activity ablated in 8 (11%) cases. The procedure was technically successful in 72 (97%) patients.

Conclusion
Patients with right-sided ATs had expectedly more dilated right atrium. This was not, however, associated with a higher prevalence of right atrial low-voltage areas. Left atrial electroanatomic remodelling in AF patients was concordant with that frequently observed in non-PH patients with AF.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Health of the Czech Republic.
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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 &gt;100 (or &gt;75th percentile) in those with low-to-moderate risk, or &gt;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

Abstract

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

Abstract

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 &lt;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&lt;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.