bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of sex on cardiovascular outcomes in RBM20 variant carriers
Authors: Cannie D , Protonotarios A , Syrris P , Sengupta A , Bilinska Z , Arana Achaga X , Barriales-Villa R , Garcia-Pavia P , Gimeno J , Merlo M , Wahbi K , Fatkin D , Mogensen J , Rasmussen T B , Elliott P 
Published: October 2022

Abstract

Background
Variants in the RBM20 gene cause dilated cardiomyopathy and may be associated with a poor prognosis.

Objectives
To determine disease penetrance, the risk of adverse events and the influence of sex on outcomes in RBM20 variant carriers.

Methods
Consecutive probands and relatives carrying pathogenic or likely pathogenic RBM20 variants were retrospectively recruited from 12 cardiomyopathy units. The primary endpoint was a composite of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF). MVA and ESHF endpoints were also analysed separately and males and females compared.

Results
Longitudinal follow-up data were available for 163 RBM20 variant carriers (82 male, median age 36.5 years, median follow-up 77.6 months). 10/163 had an MVA event at baseline. 30/153 without baseline MVA (19.6%) reached the primary endpoint with a trend towards worse outcomes in males (p=0.08). 16/153 (10.5%) had new MVA with no difference between males and females (p=0.92). 20/163 (12.2%) developed ESHF (17 males and 3 females; p&lt;0.001).
By the end of follow-up, 114 patients (70%) had either left ventricular systolic dysfunction (LVSD) or had experienced MVA. 22 patients received a first diagnosis of LVSD during follow-up. Disease penetrance in individuals over 40 years of age was 78.5% by last evaluation.
Eleven patients that reached the MVA endpoint had a left ventricular ejection fraction (LVEF) available within 6 months of the event. Median [IQR] contemporary LVEF was 30% [23.75, 40%]. 5/11 patients had a contemporary LVEF &gt;35%. 1/11 had a contemporary LVEF &gt;45% (a female, 1st degree relative presenting with sustained ventricular tachycardia and an LVEF of 65%).

Conclusions
RBM20 variants are highly penetrant. The risk of MVA in male and female RBM20 variant carriers is similar but male sex is strongly associated with ESHF. MVA events occur in patients with LVEF &gt;35%.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Clinical Research Training Fellowship
ACE values in the diagnosis of sarcoidosis
Authors: Kawai H , Naruse H , Sarai M , Kato Y , Sato Y , Motoyama S , Ishii J , Morimoto S , Izawa H 
Published: October 2022

Abstract

Background
In clinical practice, we often encounter the patients with sarcoidosis showing relatively high in the normal range of serum angiotensin-converting enzyme (ACE) value.

Purpose
We aimed to examine the serum ACE value of the patients with sarcoidosis and determine the new cut-off value for detecting the patients with sarcoidosis.

Methods and results
We retrospectively examined all 3781 subjects (51.1% men, 60.1±17.0 y.o.) in whom ACE was measured for any reasons including suspected sarcoidosis between 2009 and 2020 in our hospital. Of 293 patients with sarcoidosis, 101, 212, 84, and 88 were diagnosed as sarcoidosis in heart, lung, skin, and eyes, respectively. After excluding 477 patients taking ACE inhibitor and/or immunosuppression agent or those with any diseases affecting serum ACE levels, we analyzed 3304 subjects including 215 with sarcoidosis. Serum ACEs were 19.6 IU/L [IQR, 15.1–31.5] in the subjects with sarcoidosis and 10.7 [8.4–16.5] in those without (P&lt;0.01). In ROC curve analysis of ACE for diagnosis of sarcoidosis, the cut-off point was 14.7 IU/L and the AUC was 0.865. When we used the current cut-off of 21.4 or new cut-off value of 14.7, sensitivity, specificity, PPV, NPV, and accuracy were shown in Table. Finally, they were divided into four groups based on the presence of cardiac and/or extra cardiac sarcoidosis, ACE values in Group A, B, C, and D were 17.9, 20.9, 18.6, and 10.7, respectively (Figure 1).

Conclusion(s)
In the current cut-off value of serum ACE, sensitivity for detecting sarcoidosis was comparatively low, though positive predictive value was low when the new-cut-off value was used in our study. Further examinations may be needed for the patients suspected sarcoidosis with relatively high ACE in the normal range.

Funding Acknowledgement
Type of funding sources: None.
Valve disease in cardiac amyloidosis: an echocardiographic score
Authors: Aimo A , Fabiani I , Maccarana A , Vergaro G , Chubuchny V , Pasanisi E M , Petersen C , Poggianti E , Giannoni A , Spini V , Taddei C , Castiglione V , Passino C , Fontana M , Emdin M 
Published: October 2022

Abstract

Background
Cardiac amyloidosis (CA) may affect all cardiac structures, including the valves.

Methods
From 423 patients undergoing a diagnostic workup for CA we selected 2 samples of 20 patients with amyloid transthyretin (ATTR-) or light-chain (AL-) CA, and age- and sex-matched controls. We chose 31 echocardiographic items related to the mitral, aortic and tricuspid valves, giving a value of 1 to each abnormal item.

Results
Patients with ATTR-CA displayed more often a shortened/hidden and restricted posterior mitral valve leaflet (PMVL), thickened mitral chordae tendineae and aortic stenosis than those with AL-CA, and less frequent PMVL calcification than matched controls. Score values were 15.8 (13.6–17.4) in ATTR-CA, 11.0 (9.3–14.9) in AL-CA, 12.8 (11.1–14.4) in ATTR-CA controls, and 11.0 (9.1–13.0) in AL-CA controls (p=0.004 for ATTR- vs. AL-CA, 0.009 for ATTR-CA vs. their controls, and 0.461 for AL-CA vs. controls). Area under the curve values to diagnose ATTR-CA were 0.782 in patients with ATTR-CA or matched controls, and 0.773 in patients with LV hypertrophy.

Conclusions
Patients with ATTR-CA have a prominent impairment of mitral valve structure and function, and higher score values. The valve score is quite effective in identifying patients with ATTR-CA among patients with CA or unexplained hypertrophy.

Funding Acknowledgement
Type of funding sources: None.
Indexing calcium score of the aortic valve to the annulus area improves the grading of aortic stenosis severity in patients within the grey zone of aortic valve calcification
Authors: Gomes D , Reis Santos R , Freitas P , Presume J , Mendes G , Coutinho Santos A , Guerreiro S , Abecasis J , Ribeiras R , Andrade M J , Campante Teles R , Saraiva C , Mendes M , M Ferreira A 
Published: October 2022

Abstract

Introduction
Calcium score of the aortic valve (CaScAoV) is recommended as a supporting tool to assist in the grading of aortic stenosis (AS) severity when echocardiographic assessment is inconclusive. However, a significant proportion of patients have CaScAoV values within a “grey zone” between the “unlikely” and “likely” thresholds. The purpose of this study was to assess the potential usefulness of indexing CaScAoV to the area of the aortic annulus, in order to improve the discriminative power of CaScAoV in this subset of patients.

Methods
Consecutive patients evaluated at a single center TAVI program were retrospectively identified and included in the analysis if cardiac CT and echocardiography were performed within a 6-month timeframe. Those with LVEF &lt;50%, indexed stroke volume &lt;35 ml/m2, rheumatic heart disease, or bicuspid aortic valves were excluded. Severe AS was defined as mean transvalvular gradient ≥40 mmHg. The likelihood of severe AS assessed by CT was categorized according to the guideline-recommended sex-specific CaScAoV thresholds. Patients were considered to be in the “grey zone” if their CaScAoV values were between 800–1200 for women, and between 1600–2000 for men.

Results
A total of 655 patients were included (282 men (43.1%), median age 83 years [IQR 79–86]). AS was considered severe by echocardiographic criteria in 587 patients (89.6%), and moderate in the remainder. Median transvalvular gradient was 49 mmHg (IQR 43–59), and median CaScAoV values were 3329 (IQR 2356–4500) for men, and 1995 (IQR 1462–2781) for women.
Overall, 77 patients (11.7%) had CaScAoV values in the “grey zone”, of which 24 (31.2%) had moderate AS (Figure 1). Patients within this region of uncertainty were no different form the others in terms of age, sex, annulus size and body surface area.
In this subset of patients, indexing CaScAoV to aortic annulus area showed good discriminative power to identify severe AS (AUC 0.69, 95% CI 0.56–0.81, p=0.008). Using previously established thresholds (&gt;300 AU/cm2 for women and &gt;500 AU/cm2 for men), 48 patients (62.3%) were correctly reclassified (net reclassification index of 0.45, p=0.03). These findings were similar for both sexes.

Conclusion
In patients undergoing cardiac CT for known or suspected severe AS with CaScAoV values within the “grey zone”, indexing CaScAoV to the area of the aortic annulus improves the classification of AS severity and may decrease diagnostic uncertainty.

Funding Acknowledgement
Type of funding sources: None.
Association of cardiac amyloidosis with valvular heart diseases – a nationwide analysis
Authors: Seri A , Baral N , Kambalapalli S , Kattubadi A , Htwe K , Kunadi A , Moza A , Volgman A 
Published: October 2022

Abstract

Background
Association of cardiac amyloidosis (CA) with aortic stenosis (AS) is well known. There is limited data on the association of CA with other valvular heart diseases like aortic regurgitation (AR), mitral stenosis (MS), mitral regurgitation (MR), tricuspid stenosis (TS), tricuspid regurgitation (TR), pulmonary stenosis (PS) and regurgitation (PR).

Purpose
To assess the associations between valvular heart diseases and cardiac amyloidosis.

Methods
This is a retrospective observational study from hospitalizations between January 1, 2016, and December 31, 2019, using the National Inpatient Sample (NIS), the largest all-payer public database of hospital care data in the United States. We looked into associations between valvular heart diseases (VHD) and CA.

Results
From 2016 to 2019, a total of 4999 patients with a history of CA, 16,711 MS, 361,864 MR, 380,072 AS, 89,452 AR, 194 TS, 104,151 TR, 853 PS, 13,277 PR were identified. Compared to those without any history of CA, those with a history of CA had significantly higher associations with MR (6.4% vs 1.3%, p&lt;0.001), AS (3.6% vs 1.3%, p&lt;0.001), AR (1% vs 0.3%, p&lt;0.001), TS (0.02% vs 0, p&lt;0.033), TR (2.7% vs 0.4%, p&lt;0.001), PR (0.4% vs 0.1%, p&lt;0.001). Mean age of patients with history of CA in MS (73.7 years), MR (75.2 years), AS (81.4 years), AR (77.1 years), TS (82 years), TR (77.3 years), PR (78.1 years). Compared to males, females had higher incidence of MS (0.1% vs 0.03%, p&lt;0.001) and lower incidence of AS (1.2% vs 1.6%, p&lt;0.001) and AR (0.3% vs 0.4%, p&lt;0.001).

Conclusion
There was a significantly higher association between CA and MR, AS, TR. Comparatively, patients with CA and MS were younger than those with other VHD.

Funding Acknowledgement
Type of funding sources: None.
Prognostic implications of biventricular uptake of bone tracers at planar scintigraphy in transthyretin cardiac amyloidosis
Authors: Porcari A , Pagura L , Canepa M , Biagini E , Cappelli F , Tini G , Dore F , Longhi S , Sciagra' R , Fontana M , Gillmore J , Rapezzi C , Merlo M , Sinagra G 
Published: October 2022

Abstract

Background
The prognostic role of bone tracer uptake in transthyretin cardiac amyloidosis (ATTR-CA) is controversial. A further characterization of cardiac retention measured by Perugini scale with differentiation between biventricular (BiV) and isolated left ventricle (LV) uptake has never been attempted previously.

Purpose
The study investigated the potential prognostic significance of BiV uptake in ATTR-CA.

Methods
In this multicentre, observational study, we analysed data of ATTR-CA patients who underwent bone tracer scintigraphy with acquisition of both planar and single photon emission computed tomography (SPECT) imaging. Cardiac uptake was defined according to the Perugini visual scale. Planar BiV uptake was defined according to right ventricle (RV) uptake: 0= absent, 1= &lt; bone, 2= equal to bone, and 3= &gt; bone and confirmed by SPECT imaging. The primary outcome was a composite of cardiac death or hospitalization for heart failure. The secondary outcome was all-cause mortality.

Results
All 124 ATTR-CA patients enrolled had LV and RV free wall uptake on SPECT images. Of them, 93 (75%) had BiV uptake visible on planar scintigraphy. BiV uptake was found in 14%, 70%, and 92% of Perugini grade 1, 2 and 3 respectively. Compared to those with isolated LV uptake, patients with BiV uptake were older (81 vs 77 years, p=0.006) and more frequently in NYHA≥3 (32% vs 10%, p=0.018). During a median follow-up of 21 months, BiV uptake was associated with a greater occurrence of the primary outcome compared to isolated LV uptake (40% vs 19%, p=0.021), whereas the Perugini scale was not (p=0.2) (Figure 1). At multivariable analysis, NYHA class ≥3 (hazard ratio [HR] 8.1, p=0.007), eGFR &lt;60 ml/min (HR 2.1, p=0.025) and higher degree of RV uptake (HR 1.69, p=0.007) emerged as independent prognostic parameters. In an external cohort of 463 ATTR-CA patients with a median follow-up of 30 months, planar BiV uptake was independently associated with all-cause mortality, with an incremental risk in higher grades of RV uptake (p&lt;0.001) (Figure 1).

Conclusions
The presence of BiV uptake at planar scintigraphy identified ATTR-CA patients with worse cardiovascular and global outcomes (Figure 2), potentially serving as a novel prognostic marker.

Funding Acknowledgement
Type of funding sources: None.
Quantification of aortic valve calcification in contrast enhanced computer tomography
Authors: Laohachewin D , Hein M , Ruile P , Jander N , Neumann F J , Minners J 
Published: October 2022

Abstract

Introduction
Aortic valve calcification (AVC) is linked to higher gradients and worse prognosis in aortic valve stenosis. Current guidelines recommend calcium scoring of the aortic valve as additional factor for decision making in low-flow, low-gradient aortic stenosis. Calcium Scoring is performed by native computed tomography (CT). For planning of interventional valve replacement (TAVR) a second scan with contrast agent (CECT) is needed at the cost of additional radiation exposure and work up time. The aim of this study is to assess and validate an estimate conversion factor of aortic valve quantification by using CECT without native imaging.

Methods
The Agatston score was measured on native CT in 45 patients and used as a reference. In contrast enhanced CT, mean aortic attenuation values in Hounsfield units (HU) were determined by placement of a region of interest in the ascending aorta with a standard deviation of 4xHU for calcification threshold. AVC was segmented semi-automatically. A conversion formula was created by plotting of native Agatston score versus aortic valve calcification segmented on contrast enhanced CT and linear regression. Validation of calculated conversion formula was established by Intra-class coefficient (ICC) and Bland Altman analysis.

Results
The linear regression model yielded an Agatston score conversion formula of 691 + 1.83 × AVCCECT. Validation of the formula in a validation cohort (n=20) showed high agreement (r2=0.802, ICC 0.915 (CI 95%: 0.786–0.966) p&lt;0.001, p=0.055).

Conclusion
Approximation by our calculated conversion factor from contrast enhanced CT has shown excellent reliability to determine aortic valve calcification. Further studies are needed to extend this finding to larger cohorts and diverse clinical environments.

Funding Acknowledgement
Type of funding sources: None.
Neutrophile-lymphocyte ratio and outcome in takotsubo syndrome
Authors: Zweiker D , Pogran E , Gargiulo L , El-Razek A , Vosko I , Rechberger S , Bugger H , Christ G , Bonderman D , Kunschitz E , Zirlik A , Bauer A , Metzler B , Steinwender C , Huber K 
Published: October 2022

Abstract

Introduction
Takotsubo syndrome (TTS) is an important form of acute heart failure with significant risk of acute complications and death. In this analysis we sought to identify predictors for in-hospital clinical outcome in TTS patients by concentrating on routine laboratory parameters at admission.

Methods
In this analysis from the Austrian national TTS registry, univariable and multivariable analyses were performed to identify significant predictors for severe in-hospital complications requiring immediate invasive treatment or leading to irreversible damage, such as cardiogenic shock, intubation, stroke, arrhythmias and death. Furthermore, the influence of identified predictors with long-term survival was evaluated.

Results
A total of 338 patients (median age 72 years, 86.9% female) from 6 centres were included. Severe in-hospital complications occurred in 14.5% of patients, including cardiogenic shock (9.8%), death (3.3%) and intubation (1.2%), respectively. Patients with complications during the hospital stay had more prevalent chronic kidney disease (CKD), were less often previous smokers and TTS was less often preceded by an emotional trigger. C-reactive protein and neutrophile lymphocyte ratio (NLR) was higher in patients with complications, and midventricular ballooning and reduced left ventricular ejection fraction (LVEF) were more prevalent. In multivariable analysis, high NLR (OR 1.04 [95% CI 1.02–1.07], p=0.009) and low LVEF (OR 0.92 [0.90–0.95] per %, p&lt;0.001) remained significant predictors for severe in-hospital complications. Both the highest NLR tercile and the lowest LVEF tercile were associated with significantly reduced 5-year survival.

Discussion
Low LVEF and high NLR at admission were independently associated with increased in-hospital complications and reduced long-term survival in TTS patients. NLR is a new easy-to-measure tool to predict worse short and long-term outcome after TTS.

Funding Acknowledgement
Type of funding sources: None.
Molecular and haemodynamic interplay in bicuspid aortic valve aortopathy: segmental differences across the aortic circumference
Authors: Sophocleous F , De Garate E , Bigotti M G , Anwar M , Chamorro-Jorganes A , Rajakaruna C , Bucciarelli-Ducci C , Caputo M , Emanueli C , Biglino G 
Published: October 2022

Abstract

Background
Bicuspid aortic valve (BAV) patients develop ascending aortic (AAo) dilation. The pathogenesis of BAV-aortopathy (genetic vs. hemodynamic) remains unclear.

Purpose
To identify regional changes around the AAo wall in BAV patients with aortopathy integrating clinical imaging and molecular data.

Methods
BAV patients with aortopathy (n=20) were recruited prospectively to surgically collect aortic tissue and perform four-dimensional cardiac magnetic resonance (CMR) scans. Molecular markers were measured analysing the tissue biopsies (n=15) and wall shear stress (WSS) across the AAo circumference was calculated from the 4D CMR data (n=11 patients, and n=7 additional healthy volunteers for comparison). Dilated (anterior/right) vs. non-dilated (posterior/left) circumferential segments were profiled for whole genomic microRNAs (Next Generation RNA-Sequencing, miRCURY LNA PCR), proteins content (Tandem Mass Spectrometry) and elastin fragmentation and degeneration (histomorphometric analysis). Picture 1 summarises the study approach (including a map of the AAo divided in the following segments: A=anterior, AR=anterior-right, PR=posterior-right, P=posterior, PL=posterior-left, AL=anterior-left).

Results
Integrated bioinformatic analyses of RNA-sequencing and proteomic datasets identified 5 microRNAs (miR-128-3p, miR-210-3p, miR-150-5p, miR-199b-5p, and miR-21-5p) differentially expressed across the AAo circumference. Among them, three miRNAs (miR-128-3p, miR-150-5p, and miR-199b-5p) were predicted to have an effect on eight common target genes, whose expression was dysregulated according to proteomic analyses and involved in vascular endothelial growth factor signalling, hippo signaling and arachidonic acid pathway. Decreased elastic fibre levels and elastic layer thickness were observed in the dilated segments in the histomorphometric analysis. Increased WSS and flow-velocity, helical streamlines and asymmetrical flow were observed at the anterior/right wall in asymmetrically and symmetrically dilated patients (the latter exhibiting higher WSS), compared to healthy volunteers.

Conclusion
This study has newly revealed concomitant expressional dysregulation of miRNAs, proteins, and elastic fibres on the anterior/right wall in dilated BAV patients, corresponding to regions of elevated WSS, contributing to advance the understanding of the interplay of genetic and hemodynamic factors underpinning BAV aortopathy.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): British Heart Foundation and Above & Beyond
Ischemic stroke in patients with congenital heart disease and atrial fibrillation
Authors: Holmgren A , Dellborg M , Mandalenakis Z , Giang K W , Eriksson P , Fedchenko M 
Published: October 2022

Abstract

Background
Atrial fibrillation (AF) is one of the most common arrhythmias in patients with congenital heart disease (CHD). The risk of developing AF is more than 20 times higher in patients with CHD compared with non-CHD controls. However, while it is known that young non-CHD patients with AF have a low risk for ischemic stroke (IS), little is known about the risk for IS young CHD patients with AF.

Purpose
To investigate the risk of developing IS in younger patients with CHD and AF compared to non-CHD control patients with AF.

Method
Using data from the National Swedish Patient Register and Cause of Death register, all CHD and born in Sweden between 1970 and 2017 with history of AF were identified. The Swedish total population register was used to identify age and sex matched controls. Among the matched controls, non-CHD patients AF were identified and used as reference group. CHD and non-CHD patients were followed from onset of AF until index IS, death or end of study (31st December 2017). Cox proportional hazard regression model with hazard ratio (HR) and 95% confidence interval (CI) was used to estimate the risk of IS in CHD patients with AF compared with non-CHD controls with AF.

Results
A total of 951 CHD with AF and 606 non-CHD controls with AF were identified. With ages ranging from 0 to 47 years, the median age was 25.6 and 30.7 years for CHD and non-CHD respectively. In patients with CHD and AF, 2.9% of patients (n=28) developed IS during follow up (mean follow up 34 years, SD ± 11.2), compared 0.5% (n=3) in non-CHD controls with AF (mean follow up 37 years, SD ± 9.5 years). The unadjusted HR for IS in CHD patients with AF compared with non-CHD controls with AF was 4.61 (95% CI1.39–15.25). When adjusted for age, sex, hypertension and heart failure, the risk of IS was more than five times higher (HR 5.16, 95% CI 1.52–17.46) in CHD patients compared with non-CHD patients. The adjusted HR for developing IS in non-complex CHD with AF compared with matched controls was 4.56 (95% CI 1.00–20.79). For patients born 1970–1989 the HR of IS was 7.35 (95% CI 1.70–31.75).

Conclusion
In this nationwide, register-based cohort study, the absolute number of IS among younger CHD patients with AF was relatively low. However, the risk for developing IS was more than 5 times higher compared to non-CHD patients with AF; highlighting the need of stroke score models in younger population, particularly to CHD patients.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish state under an agreement between the Swedish government and city Councils