bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exaggerated elastin turnover in childhood and adolescence in Marfan syndrome – correlation with age – new insights from the AIMS trial
Authors: Iskandar Z , Dodd M , Stuart G , Caputo M , Clayton T , Chin C , Gibb J , Child A , Jin X Y , Flather M , Huang J T J , Choy A M 
Published: October 2021

Abstract

Background
Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by mutations in the Fibrillin1 gene (FBN1) that leads to impaired elastin formation and extra-cellular matrix homeostasis. Elastin synthesis and related lamellae formation in the aorta is completed in the newborn. Thereafter further elastin turnover is thought to be minimal during life. Elastin homeostasis is little studied in patients with MFS who have been reported to have reduced elastin in their aorta and are at risk of aortic dilatation and consequent life-threatening dissection. It is not clear if elastin loss is due to reduced elastin formation in utero or accelerated degradation during life. However, aortopathy develops early in MFS with 70% of patients developing aortic dilatation by the age of 20 years. Therefore, the longitudinal and circumferential aortic growth that occurs in childhood may involve elastic lamellae remodelling that is impaired in MFS. Desmosine is the cross-link component in the elastin molecule and is exclusively released from mature elastin breakdown, thus is a physiologically relevant biomarker of elastin turnover. We hypothesise that physiologic aortic growth is associated with elastic lamellae remodelling and increased elastin turnover, detected by elevated plasma desmosine (pDES), and that elastin turnover is exaggerated during the fast-growing period in MFS.

Purpose
The aims of this study were 1. To investigate the relationship between elastin turnover and age in the control subjects, and 2. To compare the elastin turnover in MFS with control subjects.

Methods
pDES was measured by stable isotope dilution LC-MS/MS in 113 MFS subjects (48% male, mean age 18.2±9.4 (SD) years), mean aortic root 33.8±2.1mm and Z-score 3.4±2.1 in the AIMS trial at baseline before intervention, and in 109 healthy controls (46% male, mean age 26.1±9.5 years).

Results
pDES levels were associated positively with age, body surface area and negatively with diastolic BP in the control group (p=0.05 and 0.21 respectively after correcting for age). In MFS subjects pDES also positively correlated with age and male sex (p&lt;0.05). Interestingly, the age-dependent association with pDES showed a peak distribution in both control and MFS groups (Figure 1) where teenage children expressed the highest pDES levels. MFS subjects had significantly higher pDES compared to controls before the age of 20 (p=0.01) but in adulthood, there was no difference (Figure 2).

Conclusion
Elastin turnover is highly dynamic before early adulthood, and peaks in adolescence and is exaggerated in MFS, suggesting that this period of growth is critical in developing aortopathy.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): British Heart FoundationTENOVUS Scotland Figure 1Figure 2
Plasma metabolomics in perioperative period of defect repair in patients with pulmonary arterial hypertension associated with congenital heart disease
Authors: Yan Y , He Y.-Y , Chen J.-W , Fu Y.-X , Liu S , Hua L , Jiang X , Xu X.-Q , Lu D , Jing Z.-C , Han Z.-Y 
Published: October 2021

Abstract

Background
The pathophysiological alterations in response to shunt correction in patients with pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) is still not clear.

Purpose
To explore the dynamic plasma metabolite profiling and its relationship with clinical characteristics in patients with CHD-PAH during the perioperative period of defect repair.

Methods
Plasma samples from 13 patients with CHD-PAH were harvested at four time points: before cardiopulmonary bypass (CPB) after anesthesia (Pre), immediately after CPB (T0), 24 h (T24), and 48 h (T48) after defect repair. The untargeted metabolomics strategy based on UPLC Q-TOF MS was used to detect the metabolites. Clinical measures were recorded at indicated time points.

Results
The sample distribution at four time points was well separated (Figure 1A, B). 193 metabolites were distinguished at different time points according to Variable Important in Projection (VIP) score (Figure 1C), enriched in pathways such as carnitine synthesis, phospholipid biosynthesis and oxidation of branched chain fatty acids (Figure 2A). 17 metabolites alterations were significantly correlated with gradients in mean pulmonary arterial pressure (mPAP) at T48 versus Pre, indicative of the response to defect correction (Figure 2B). Intriguingly, 4 out of the 17 (23.5%) metabolites including propionylcarnitine, butenylcarnitine, isobutyryl-L-carnitine and hexanoylcarnitine were enriched in oxidation of branched chain fatty acids. They were increased at both T24 and T48 (all P&lt;0.05 except propionylcarnitine with P&lt;0.05 at T24) (Figure 2C).

Conclusions
This is the first study to show the altered metabolic profiles of CHD-PAH patients in perioperative period of defect repair. Metabolites that respond to shunt correction could be a suitable non-invasive marker and would be of great value in disease monitoring and evaluating future therapeutic interventions.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): 13th Five-Year Plan–Precise Medicine–Key Research and Development Program–Clinical Cohort of Rare Disease; National Natural Science Foundation of China Figure 1. Overall analysis of metabolitesFigure 2. Shunt correction associated metabolites
Real-world, very long-term follow up survival of incident patients with pulmonary hypertension
Authors: Ferreira C , Festas T , Alves P , Freitas A , Almeida J P , Martinho S , Goncalves V , Castro G , Baptista R , Goncalves L 
Published: October 2021

Abstract

Background
Pulmonary hypertension (PH) is a clinical syndrome characterized by an increase in pulmonary artery pressure. Among the five groups of PH, pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) stand out due to their ominous prognosis without specific treatment. However, very long-term outcomes data are scarce.

Purpose
We aimed to assess the very long-term survival of PAH and CTEPH patients followed in a Portuguese PH referral center.

Methods
Between January 2009 and January of 2020, all incident PH cases were consecutively enrolled in a prospective cohort study. A total of 177 patients were followed up for a median of 5.0 [interquartile range 2.3–8.7] years. Kaplan-Meier survival analysis was used to estimate 1-, 5- and 9-year survival and multivariate regression was used to predict independent prognostic factors.

Results
Mean age was 49±20 years with a clear female preponderance (67%). The most common PH subgroups were congenital heart disease (PAH-CHD) (n=62; 35%), followed by CTEPH (n=52; 29,4%), connective tissue disease (PAH-CTD) (n=31; 17.5%), idiopathic/hereditary PAH (I/HPAH (n=22; 12.4%) and portopulmonary hypertension (PoPH) (n=8; 4.5%) (Table 1). PAH-specific drugs were used in 91% of the patients, dual combination therapy in 47.5%, and triple combination in 12.4%. The remaining 9% successfully received non-pharmacological treatment, namely cardiac surgery in PAH-CHD (n=7) and endarterectomy or angioplasty in CTEPH (n=9). Survival rates at 1-, 5- and 9-years were 97%, 80% and 66%, respectively. Age (hazard ratio [HR] 1.02; 95% CI 1.01–1.04; P=0.049), BNP [HR 2.04 (1.16–3.60); P=0.01], admission for decompensation of heart failure (HF) [HR 3.15 (1.71–5.83); P&lt;0.001] and PH type [P=0.01] were predictors of all-cause mortality. PAH-CHD had the better long-term survival (9-year survival of 83%), whereas PAH-CTD and PoPH were associated with a worse prognosis (9-year survival of 24% and 28%, respectively) (Figure 1). Regarding admissions for decompensated right HF, BNP was an independent predictor [HR 3.39 (2.12– 5.43); P&lt;0.001] and no difference was found between PH etiologies.

Conclusions
In this cohort of incident PH patients, the overall 9-year survival rate was 66%. PAH-CHD patients had better overall prognosis, while patients with PAH-CTD and PoPH had the worst prognosis. Additionally, older age, higher BNP and admission for HF were associated with higher mortality.

Funding Acknowledgement
Type of funding sources: None.
An original risk score to predict early major bleeding in acute pulmonary embolism: the Syncope, Anemia, Renal Dysfunction (PE-SARD) bleeding score
Authors: Chopard R , Piazza G , Falvo N , Ecarnot F , Besutti M , Capellier G , Schiele F , Badoz M , Meneveau N 
Published: October 2021

Abstract

Background
Improved prediction of the risk of early major bleeding in pulmonary embolism (PE) is needed to optimize acute management.

Methods
Using data from a multicenter prospective registry including 2,754 patients, we performed multivariable logistic regression analysis to build a risk score to predict early (up to hospital discharge) major bleeding events. We validated the endpoint model internally using bootstrapping in the derivation dataset by sampling with replacement for 500 iterations. We compared the performance of this novel score to that of the VTE-BLEED and RIETE models.

Results
Multivariate regression identified three predictors for the occurrence of 82 major bleeds (3.0%): Syncope (+1.5 points), Anemia defined by a hemoglobin level &lt;12 g/dL (+2.5 points), and Renal Dysfunction defined by a glomerular filtration rate &lt;60 mL/min (+1 point). The PE-SARD bleeding score was calculated by summing all the components. Overall, 52.2% of patients were classified as low bleeding-risk (score, 0 point), 35.2% intermediate-risk (score, 1–2.5 points), and 12.6% high-risk (score &gt;2.5 points). Cumulative observed bleeding rates increased with increasing risk group, from 0.9% in the low-risk group to 9.0% in the high-risk group. The C-index was 0.744 (95% CI, 0.73–0.76) and Brier score 0.028 in the derivation cohort. Similar values were calculated from internal bootstrapping. Performance of the PE-SARD score was better than that observed with the VTE-BLEED and RIETE scores (figure).

Conclusions
The PE-SARD bleeding risk score is an original, user-friendly score to estimate the risk of early major bleeding in patients with acute PE.

Funding Acknowledgement
Type of funding sources: None. Figure 1
Response to anticoagulation in chronic thromboembolic pulmonary hypertension
Authors: Campean I C , Shafran I , Sadushi-Kolici R , Panzenboeck A , Skoro-Sajer N , Lang I M 
Published: October 2021

Abstract

Introduction
Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by fibrotic thrombus in the pulmonary arteries, likely originating from pulmonary embolism. Inadequate anticoagulation is one of the suspected mechanisms of disease in CTEPH. The aim of our study was to assess phenprocoumon dosing and genetic polymorphisms of vitamin K epoxide reductase complex subunit 1 (VKORC 1) that are known to affect the dose required to reach therapeutic range.

Methods
The ratio of mean weekly phenprocoumon dose in relation to mean INR levels was assessed in CTEPH patients on phenoprocoumon oral anticoagulation for at least 6 months, compared with PAH patients. VKORC 1 (–1639, –3730) single nucleotide polymorphisms (SNPs) were determined by polymerase chain reaction (PCR).

Results
In 225 patients (167 CTEPH, 58 PAH) mean treatment duration was 51.7±44.7 months, and mean age was 62.9±13.87 years (49.7% female). Median weekly dose of phenprocoumon was 10.5 mg (IQR 9.0–16.5) for PAH vs. 14.25 mg (IQR 10.5–18.0) in the CTEPH cohort (p=0.016). Although median INR was not significantly different among the two groups (2.28 vs. 2.40 in the PAH vs. CTEPH, respectively, p=0.084), achieving the mentioned INR require significantly higher weekly doses in the CTEPH group. While distribution of VKORC1 variants was according to the Hardy Weinberg equilibrium, patients with CTEPH and VKORC1 –1639 GG homozygous wild type required significantly higher phenprocoumon doses compared with VKORC1 –1639 AA homozygous mutants (P&lt;0.001).

Conclusion
CTEPH patients require more vitamin K antagonists in relation to INR levels than PAH patients. Unmet phenprocoumon dosing requirements may be one mechanism of disease in CTEPH.

Funding Acknowledgement
Type of funding sources: None.
Population-based incidence and outcomes of acute aortic dissection in Japan
Authors: Yamaguchi T , Nakai M , Yano T , Matsuyama M , Miyamoto Y , Kodama T , Ogino H 
Published: October 2021

Abstract

Background
The population-based incidence and outcomes of acute aortic dissection (AAD) are still unknown because some patients are already dead on arrival at the hospital, and the accurate diagnosis of AAD is difficult due to the low autopsy rate for patients with cardiopulmonary arrest outside of the hospital. We performed a population-based review of all patients with AAD in a well-defined geographical area in the southern part of Japan between 2016 and 2018.

Methods
Data of all patients with AAD at our Hospital, which performs medical care for 120,000 residents, were collected retrospectively. The emergency medical service is dedicated to the transfer of all patients in this area to the MPNH. For all patients who were dead on arrival, the diagnosis of AAD was made by autopsy imaging (AI) using computed tomography. The age-adjusted incidence and mortality per 100,000 population were calculated using the Japanese population distribution model in 2015.

Results
The total incidence of AAD was 79 (type A: 64.5%, n=51). Of those, 60.8% (31/51) of patients with type A and 21.4% (6/28) with type B were dead on arrival and diagnosed by AI. The 30-day mortality rates after the onset of AAD were 74.5% (38/51) in type A and 25.0% (7/28) in type B. Excluding the dead-on-arrival patients, the 30-day mortality rates were 35.0% (7/20) in type A and 4.5% (1/22) in type B. The age-adjusted incidence and mortality of AAD per 100,000 inhabitants were 17.3 (type A: 11.3, type B: 6.0) and 9.6 (type A: 8.4, type B: 1.2), respectively. Both values were significantly higher in men than in women.

Conclusions
The population-based survey of emergency medical care for AAD showed that the age-adjusted incidence of AAD was two-fold higher than in previous reports, and the actual mortality rates after AAD onset were markedly higher due to the high incidence of dead-on-arrival.

Funding Acknowledgement
Type of funding sources: None. Representative CT images of type A AAD
The comparison of clinical features and clinical outcomes in stroke patients with atrial fibrillation and non-atrial fibrillation: a hospital-based stroke registry in Indonesia
Authors: Karunawan N H , Pinzon R T , Siswanto B B 
Published: October 2021

Abstract

Background
Atrial Fibrillation (AF) is the most common sustained cardiac arrhythmia associated with stroke. Based on the National Health Survey (Riskesdas) the prevalence of stroke in Indonesia increased from 7% in 2013 to 10.9% in 2018. Understanding the clinical features and clinical outcomes differences between AF and non-AF in stroke can help the clinician for further management.

Purpose
To compare the clinical features and clinical outcomes of stroke patients with AF and non-AF by using the data from the Bethesda Stroke Registry in Indonesia.

Methods
This cross-sectional study was based on a stroke registry, data were collected using the electronic medical record in our hospital. All patients ≥18 years of age, who developed stroke between January 1, 2011, and December 31, 2018, were included in this study. Data about clinical features and clinical outcomes were collected. The clinical outcomes included mortality, prolonged hospitalization (LOS &gt;6 days), and disability was evaluated using the modified Rankin scale (MRS). The statistical measures calculated were Chi-square-test and Fischer's exact test.

Results
Data of the total 8447 patients enrolled in the registry, data of 8248 patients who fulfilled inclusion criteria were analyzed, and AF was seen in 226 (2.7%) stroke patents. Comparing with non-AF patients, AF patients were older (47.8% vs 26.0%), higher proportion on of women (48.2% vs39.9%), higher prevalence of ischemic heart disease (16.4% vs 4.7%), loss of consciousness (37.6% vs 23.2%), aphasia (29.6% vs 13.6%) mortality (20.8% vs 10.6%), prolonged hospitalizaton (10.24 [1–80] vs 7.18 [1–73]), worse disability (67.3% vs 43.2%), p&lt;0.05. Comparing with AF patients, non-AF patients had a significantly higher prevalence of hypertension (52.9% vs 40.3%) and diabetes mellitus (33.5% vs 32.7%), p&lt;0.05. Stroke patients with AF was significantly associated with higher in-hospital mortality (RR: 1.19, 95% CI: 1.05–1.35, p&lt;0.001), worse disability (RR: 1.16, 95% CI: 1.11–1.22, p&lt;0.001), and prolonged hospital stay RR: 1.39, 95% CI: 1.22–1.59, p&lt;0.001) than in stroke patents with non-AF.

Conclusions
AF in stroke affected the poor outcomes by contributing to higher in-hospital mortality, prolonged hospitalization, and worse disability. Older age, Women and IHD were more strongly associated with Stroke n AF than non AF

Funding Acknowledgement
Type of funding sources: None.
Prediction of the functional significance of the left main stenosis using frequency domain optical coherence tomography
Authors: Vlad D , Bouki P , Nakas A , Diamantakis E , Kotsakis A , Baroutsi K , Toutouzas K 
Published: October 2021

Abstract

Background
Frequency domain optical coherence tomography (FD-OCT) has been used for the assessment of non-ostial left main coronary artery stenosis (LM). However, no study has evaluated the use of this imaging technique for the prediction of functional significance of LM lesions determined by the fractional flow reserve (FFR).

Purpose
The aim of this study was to assess the safety and diagnostic efficacy of FD-OCT in identifying functional severity of the LM stenosis determined by (FFR).

Methods
One hundred one patients with LM lesion (20–70% diameter stenosis angiographically) underwent FFR measurement and FD-OCT imaging of the LM. The following parameters were measured by FD-OCT in the LM: reference lumen area (RLA), reference lumen diameter (RLD), minimum lumen area (MLA), minimum lumen diameter (MLD), % lumen area stenosis, % diameter stenosis.

Results
The LM lesions were visible and measurable by FD-OCT in 88/101 (87.1%) patients. However lesions with ostial location were analyzable by FD-OCT only in 17/30 (56.4%) patients (Figure 1). FFR at maximum hyperemia was ≤0.80 in 39/88 (44.3%) patients. FFR values were correlated significantly with FD-OCT derived LM lumen parameters. Receiver operating characteristic curves showed that an MLA cutoff value of 5,38 mm2 had the highest sensitivity and specificity of 82% and 81% respectively (Figure 2A), followed by an MLD of 2.43 mm (sensitivity 77%, specificity 72%) (Figure 2B) and an %AS of 60% (sensitivity 72%, specificity 72%) (Figure 2C) for predicting FFR ≤0.80.

Conclusions
FD-OCT is safe and feasible imaging technique for the assessment of a LM stenosis except the ostial LM lesions which are analyzable in half of the cases. An FD-OCT derived MLA of ≤5.38 mm2 strongly predicts the functional severity of a LM lesion.

Funding Acknowledgement
Type of funding sources: None. Angiography and OCT image of LM stenosisROC curves of MLA, MLD and AS
Extracardiac coronary steal induced by upper limb hyperemia: a feature of internal mammary artery arteriogenesis
Authors: Bigler M R , Buffle E , Stoller M , Grossenbacher R , Tschannen C , Seiler C 
Published: October 2021

Abstract

Introduction
Function of naturally existing internal mammary artery (IMA)-to-coronary artery anastomoses has been shown by augmented blood supply to the coronary collateral circulation in response to IMA occlusion. Theoretically, this functional connection is invertible and can cause coronary steal, the verification of whose hypothesis would provide alternate proof to the mentioned functional evidence.

Method
This was a prospective observational study including 40 patients with chronic coronary syndrome and IMA occlusion, and 40 propensity score matched controls (placebo group) without IMA occlusion. Primary study endpoint was the inter-group difference in coronary collateral function (i.e., collateral flow index, CFI) as obtained at 30, 45 and 60 seconds following a proximal coronary artery balloon occlusion. CFI is the ratio between simultaneous mean coronary occlusive pressure divided by mean aortic pressure both subtracted by central venous pressure. To provoke a steal phenomenon, upper limb hyperemia was induced by upper arm blood pressure cuff deflation following a 5-minute supra-systolic inflation ipsilateral to the sensor-wired coronary artery with release immediately after the first CFI measurement.

Results
Between the first and the second CFI-measurement, CFI change (i.e., CFI@45s minus CFI@30s) was absent in the verum group while there was CFI recruitment in the placebo group: 0.000±0.023 and +0.009±0.013, respectively; p=0.032.

Conclusion
Among patients with artificial IMA occlusion, induction of ipsilateral upper limb hyperemia provokes extracardiac coronary steal as expressed by temporarily absent collateral recruitment as it normally takes place without upper limb hyperemia.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Swiss National Sciences Foundation
Comparison of cardiovascular outcomes of moderate to severely calcific de novo coronary lesion preparation for stent implantation using rotational atherectomy in conjunction with cutting balloon versu
Authors: Gedela M G , Giustino G G , Kyaw H K , Johal G J , Hooda A H , Sartori S S , Qiu H Q , Mehran R M , Kini A K , Sharma S S 
Published: October 2021

Abstract

Background
Previous studies showed the combined rotational atherectomy (RA) and cutting balloon angioplasty (CBA) strategy was associated with favourable cardiovascular outcomes compared to RA and plain balloon angioplasty (PBA) for adequate lesion preparation before stent implantation in moderate to severely calcified coronary lesions. However, these studies were limited by small sample size.

Purpose
To assess clinical outcomes in a large group of patients with moderate to severely calcified de novo severe coronary artery stenoses using RA followed by CBA (RA+CBA) compared to RA followed by PBA (RA+PBA) before 2.5–3.5 mm diameter stent implantation.

Methods
We conducted a retrospective analysis of 1852 patients with moderate to severely calcified de novo severe coronary artery stenosis who underwent RA+CBA (n=372) or RA+PBA (n=1480) before 2.5–3.5 mm stent implantation. Death, myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis (ST), and major adverse cardiovascular events (MACE) were calculated at 1-year. Standard multivariable covariate adjusted hazard ratios (HR) were performed.

Results
At 1-year follow-up, the unadjusted MACE [HR: 1.58 (1.14–2.21); p=0.007] was significant in RA+CBA group compared to RA+PBA group, even after adjusted for multiple variables [HR: 1.61 (1.11–2.35); p=0.013] (Figure 1A). This was mainly driven by TVR [Unadjusted HR: 1.76 (1.16–2.68); p=0.008 and adjusted HR: 1.64 (1.01–2.67); p=0.045] (Figure 1B). However, other adjusted outcomes including death [HR: 1.25 (0.63–2.50); p=0.521], MI [HR: 1.71 (0.77–3.77); p=0.188], and ST [HR: 2.11 (0.64–6.95); p=0.221] were not significant between both groups. There was no significant difference in complications including coronary artery dissection, side branch closure, coronary perforation, slow flow/no flow, abrupt vessel closure, post procedure MI, blood transfusion or bleeding in between the two groups.

Conclusion
In moderate to severely calcific de novo severe coronary artery stenosis lesion preparation before 2.5–3.5 mm stent implantation, RA+CBA strategy is associated with a higher risk of major adverse cardiovascular events compared to RA+PBA strategy at 1-year follow-up.

Funding Acknowledgement
Type of funding sources: None. Figure 1