bluuebunny/crossref_metadata_2025_split huggingface dataset:
miRNAs as a tool for the diagnosis of suspected Brugada Syndrome
Authors: Cabiati M , Persiani E , Del Ry S , Piacenti M , Rossi A , Zucchelli G , Solrarino G , Nesti M , Notarstefano P , Pieragnoli P , Morales M A , Fernandez S , Vozzi F 
Published: May 2024

Abstract

Background/Introduction
Brugada syndrome (BrS) is a life-threatening arrhythmogenic disease that can lead to sudden unexplained death/cardiac arrest in otherwise healthy individuals. ECG represents the gold standard for the diagnosis. In 30% of cases, however, the syndrome is diagnosed only after a provocative test with sodium channel blockers [1]. Among the different approaches to support diagnosis, circulating biomarkers such as miRNAs may represent a tool that can provide a biological signature of the syndrome in patients with suspected BrS.

Purpose
Within the BrS and Artificial Intelligence Applications to Diagnosis system study, we collected and analyzed blood samples from patients with suspected BrS undergoing provocative tests aiming to assess whether miRNAs may be potential markers to identify the syndrome.

Methods
Patients undergoing provocative tests with sodium channel blockers (i.e., ajmaline, flecainide) were classified as positive (15 patients) and negative (13 patients) based on the test results. Blood samples were obtained when a Type-1 ECG pattern developed (for positive) or at the end of the provocative test without any electrographic changes (negative). miRNAs were extracted from circulating exosomes, obtained by blood samples, using a dedicated and innovative assay (exoRNeasy mini/midi kit, QIAGEN). They were quantified and quality tested by Agilent 2100 Bioanalyzer RNA assay; miRNA-seq was carried out with NovaSeq 6000 (Illumina, San Diego, CA). Data were analyzed through web-based platforms for network visual analytics (mirNET 2.0).

Results
The presence of 8 small RNAs up-regulated was reported in the positive group (hsa-miR-155-5p ,hsa-miR-10a-5p, hsa-miR-29a-3p, hsa-miR-142-5p, hsa-miR-30a-5p, hsa-miR-126-5p, hsa-miR-95-3p, hsa-miR-126-3p), with a log fold-change between 6.4 (as for hsa-miR-95-3p) and up to 615.0 (as for hsa-miR-126-3p) (Table 1). The network analysis results (Figure 1) on this group of miRNAs showed their involvement, among the others, in response to cytokine and muscle development (in terms of function analysis) and Ca2+pathway modulation (in terms of pathway analysis).
Conclusion(s)
In this work, a miRNA analysis of patients undergoing provocative tests for Type-1 BrS diagnosis was performed. Our results show a set of potential miRNAs that could be used to identify Type 1 BrS patients in whom the typical ECG pattern is basally lacking. Although further experiments and validation on a larger number of samples are necessary, our results could identify these miRNAs as potential early markers in patients with a suspected Type-1 BrS diagnosis.Upregulated miRNAs in BrS patientsMiRNA network analysis
Cardioneuroablation for asystolic reflex syncope with or without the use of extra cardiac vagal stimulation-one year follow-up results
Authors: Piotrowski R , Baran J , Sikorska A , Krynski T , Niedzwiedz M , Kulakowski P 
Published: May 2024

Abstract

Background
Extra-Cardiac Vagal Stimulation (ECVS) during cardioneuroablation (CNA) has been introduced to confirm total vagal denervation – a clear intra-procedural end-point. However, whether the use of ECVS is associated with better outcome than simple intra-procedural assessment of CNA-induced changes in basic ECG parameters, has not been established.

Purpose
To compare one-year efficacy of CNA performed with versus without ECVS.

Methods
This retrospective analysis included 90 patients (age: 37±12 years, 39 males) divided into 2 groups: ECVS(+) (n=41, general anesthesia and total muscle relaxation, settings: 50 Hz, 0.05 ms, 1 V/kg (&lt;70V) for 5 s) and ECVS(-) group (n=49, light sedation). CNA strategy was the same in all patients and was based on presumed anatomical localization of ganglionated plexi, combined with identification of ablation targets at sites with fragmented bipolar atrial electrograms. The end-point in the ECVS (+) group was complete vagal denervation, confirmed by ECVS, whereas in the ECVS (-) group - significant (&gt;30%) acceleration of sinus rate. The primary endpoint was syncope recurrence during one-year follow-up.

Results
Both groups were comparable concerning clinical and demographic parameters. Primary endpoint occurred in 4 (10%) patients in the ECVS(+) group and in 7 (14%) patients in the ECVS(-) group (p=0.7481) (Figure). No complications were reported.

Conclusions
These preliminary results suggest that the use of ECVS only slightly improves the one-year CNA efficacy, however, prospective larger studies and longer follow-up are needed to confirm these initial findings.
Repolarization gradient induces local depolarization abnormalities in Brugada Syndrome
Authors: Garibaldi S , Tirabasso D , Latrofa S , Hartwig V , Nesti M , Panchetti L , Mirizzi G , Startari U , Zaurino N , Morelli M S , Passino C , Emdin M , Piacenti M , Giannoni A , Rossi A 
Published: May 2024

Abstract

Background
Transmural voltage gradient in right ventricular outflow tract (RVOT) induces diagnostic ECG-phenotype in Brugada syndrome(BrS). Moreover, RVOT depolarization abnormalities have been described as contributors to BrS phenotype and arrhythmogenesis.

Purpose
To investigate the effect of ajmaline administration on J-elevation of RVOT unipolar signals in BrS patients. Moreover, we wanted to assess whether ajmaline-induced unipolar J-point elevation variations induced local depolarization abnormalities.

Methods
21 BrS patients with spontaneous type-1 ECG pattern were enrolled. Due to the absence of BrS ECG pattern at the study, patients underwent RV endocardial mapping with the CARTO3 system, before (PRE) and after (POST) ajmaline administration. The PRE and POST data were exported from CARTO and converted into Matlab format using OpenEP. J-elevation for each point was calculated as the amplitude of the unipolar signal at J wave with respect to baseline. Activation time (AT) of each point was defined as the difference between local depolarization (minimum dV/dt of the unipolar signal) and surface ECG depolarization (time of the minimum signal on V2). With an automatic algorithm, corresponding PRE and POST points were selected. The difference between POST and PRE of each parameter was calculated to obtain the differential values delta-J and delta-AT. Differential values were then interpolated on the mesh of each subject to obtain 3D maps. The deltaJ map was divided into four intervals based on quartiles. We then selected a ROI 'IN' on a region with the greatest deltaJ variation, and a second ROI 'OUT' on the zone of lowest variation. The same ROIs were applied to the deltaAT map. The mean value of the respective differential parameters was extracted in each ROI.

Results
Greatest delta-J values were found in the RVOT/anterior wall. delta-J in the ROI 'IN' was greater than in the ROI 'OUT' (1.68 [1.11-2.28] vs 0.56 [0.38-0.93] mV, p&lt;0.001). delta-AT in the ROI ‘IN’ was greater than in the ROI ‘OUT’ (27.96 [20.39-44.89] vs 7.62 [4.24-16.69] ms, p&lt;0.001). A good correlation was found between delta-J and delta-AT, considering the data for the two ROIs together (Spearman R coefficient=0.71, p&lt;0.001).

Conclusions
Our study shows that the repolarization gradient, evaluated by localized delta-J increase in RVOT, justifies BrS ECG phenotype and local depolarization abnormalities. A strong correlation was present in these RVOT areas between J-elevation variation and slow conducting zones.
Computed tomography as a predictive tool for ventricular tachycardia
Authors: Kowalewski C , Nunez-Garcia M , Bouteiller X , Vlachos K , Benali K , Monaco C , Bouyer B , Ly B , Sermesant M , Yokoyama M , Pambrun T , Derval N , Cochet H , Haissaguerre M , Jais P 
Published: May 2024

Abstract

Background
Sudden cardiac death is the main cause of mortality worldwide. It is often linked with ventricular tachycardia (VT). To prevent VT, high-risk patients are typically equipped with intracardiac defibrillators (ICDs). Currently, left ventricular ejection fraction (LVEF) is the standard for determining a patient's risk level.

Objective
We hypothesized that the use of imaging software analyzing cardiac CT-scans could enhance the detection of patients with an increased risk of VT.

Methods and Results
In this study, 132 patients with ischemic cardiomyopathy (average age 66.2±11.4 years, with an average LVEF of 36.6±10.3%), all with implanted cardiac devices, underwent CT scans. We developed software to automatically analyze the heart's wall tissue thickness, cardiac fat, and calcification levels (Figure.1.A). A viable cardiac wall thickness of less than 3mm typically indicates a ventricular wall predominantly composed of scar tissue with minimal viable tissue remaining. In contrast, a viable wall thickness of less than 5mm includes regions with more viable tissue and therfore represents the total scar. Over an average follow-up of 6.6 years (79.8 ± 30.5 months) via live telemedicine, we observed that patients with VT had a significant difference in wall thickness ratio (3mm/5mm; no VT 0.31±0.18 vs, VT 0.44±0.18, p&lt;0.01)) and higher calcification (0.10±0.38ml vs. 0.47±1.57ml, p=0.039). The amount of cardiac fat did not significantly differ between the no VT and VT groups (1.14±1.38ml vs.1.21±1.01ml, p=0.771). Logistic regression determined a critical cutoff for wall thickness at a ratio of 0.3 for 3mm and 5mm thickness. Kaplan Meyer analysis contrasted this wall thickness ratio of 0.3 (figure.1.B) against the established LVEF threshold of 35% (figure.1.C) for predicting VT-free survival, revealing a notable disparity favoring wall thickness ratio (p&lt;0.01) over LVEF (p=0.77).

Conclusions
The findings suggest that a higher proportion of regions of thin viable tissue or dense scar in the total scar is a more effective predictor of VT-free survival than LVEF, potentially improving the identification of patients at risk for sudden cardiac death.Figure. 1
Sudden cardiac death as first manifestation of cardiovascular disease - a Danish nationwide study
Authors: Skjelbred T , Warming P E , Kroell J , Andersen M P , Torp-Pedersen C , Winkel B , Tfelt-Hansen J , Lynge T H 
Published: May 2024

Abstract

Background and objective
Sudden cardiac death (SCD) is a leading cause of death and previous studies have shown that approximately half of all cases have no known history of cardiovascular disease (CVD). Epidemiological studies of SCD cases of all ages are sparse. The aim of this study was to examine differences in incidence rates, clinical characteristics, comorbidities, and socioeconomic status between SCD cases with and without a known history of cardiovascular disease.

Methods
All 54,028 deaths in Denmark in 2010 were reviewed. Autopsy reports, death certificates, discharge summaries, and nationwide health and social registries were reviewed to identify cases of SCD. Information on previous history of CVD was extracted from the comprehensive Danish nationwide health and social registries.

Results
A total of 6,867 SCD cases were identified, of which 3,056 (44.5%) had no history of cardiovascular disease and 3,811 (55.5 %) had a history of CVD. Incidence rates of SCD increased with age and were higher in cases of SCD with a history of CVD across all age groups. The difference in incidence of SCD between persons with and without history of cardiovascular disease decreased with increasing age with incidence rate ratios ranging from 11.7 (95 % CI: 5.51 – 25.00) to 3.19 (95 % CI: 2.79-3.64) in those age 0-29 years and &gt;90 years, respectively. Persons living in a low-income household (OR: 0.76, 95 % CI: 0.58-0.98, p=0.037), persons living in rural municipalities (OR: 0.87, 95 % CI: 0.78-0.98, p=0.021), and persons living in single-person households (OR: 0.73, 95 % CI: 0.66-0.82, p=0.037) had a lower likelihood of having a CVD prior to SCD.

Conclusion
This is the first nationwide study of SCD cases with and without history of CVD across all ages. SCD cases with no known CVD were significantly younger, more female and had less comorbidities. Although a substantial amount of SCD cases occur in persons with no known CVD, SCD is more common in the populations of persons with a history of CVD. Socioeconomic factors such as low income, living alone and living in rural communities were associated with a lower risk of having a cardiovascular diagnosis prior to SCD.Crude numbers and incidence rates of SCDIncidence rate ratios
The prevalence and clinical features of syncope in patients with concealed Brugada Syndrome
Authors: Hunuk B , Cagac O , Turan O E , Besiroglu F , Kozan O 
Published: May 2024

Abstract

Background
Brugada Syndrome (BS) is an inherited rhythm-disorder with risk of sudden-cardiac-death defined by a specific ST-segment elevation pattern in precordial ECG-leads either spontaneous or provoked by Na-channel-blocker-drug-provocation-test with Ajmaline. Scarce data denote that the prevalence of non-arrhythmic syncope is high in BS and leads to diagnostic confusions. Head-up tilt test (HUT) is a diagnostic tool used to assess autonomic function in patients with suspicious syncopal events.

Purpose
Our aim was to elucidate the frequency of non-arrhythmic syncope in BS patients, compare it with non-BS population with suspicious syncope and reveal possible clinical relations.

Methods
Adult patients with an history of Ajmaline-induced BS and patients evaluated for suspicious syncope with non-arrhyhtmic-features without BS less than 55-years-old were prospectively and consecutively evaluated with resting and higher-inter-costal-space-ECGs (HICS-ECGs), cardiac-examination and routine HUT in our center. After the exclusion of subjects with resuscitated-sudden cardiac-death/documented-malignant-dysrhythmia, any cardiac-disease, anti-arrhythmic-use, bundle-branch-blocks, pre-excitations and ventricular hypertrophies; 52 BS(+) subjects ([mean±SD] age, 33,6±14, [range]18-55 years) (male n [%overall]:33 [63.2%]) and 35 age-sex matched BS(-)subjects ([mean±SD] age, 34,1±13, [range]18-55 years) were enrolled in the study. All ECGs and HUT test results were interpreted manually by two experienced cardiologists for BS and Brugada-type-ECG-patterns (BTEPs).

Results
The clinical characteristics of patients with and without BS and statistical findings are presented in Table-1. BS(+) patients were slimmer, revealing more BTEPs by baseline HICS-ECGs. Baseline heart-rates were lower, PR-intervals and P-wave-duration were significantly higher in BS(+) patients. HUT-positivity of BS(+) patients were significantly higher [(39% (n: 20 [male n: 13]) vs 19% (n: 7 [male n: 4]) (p= 0,01)] revealing significantly more mixed-syncope and orthostatic hypotension response in BS(+) subjects. No cardioinhibitory response was revealed.

Conclusions
Non arrhtymic syncope is found to be highly prevalent in middle-aged-subjects and especially males with BS (+) without an apparent cardiac-disorder. Knowing this considerably important clinical aspect might effect risk stratification algorithms and might prevent unnecessary high-risk interventions and device decisions. Non-invasive indices regarding the delayed conduction features in ECG characteristics of BS(+) patients and a higher vagal state might be proposed as one of the probable mechanisms revealing the higher prevalence of non-arrhythmic-syncope in BS.Table-1
Clinical validation of a novel digital twin framework for ventricular functional substrate simulation in post-infarction patients
Authors: Parollo M , Biasi N , Seghetti P , De Lucia R , Di Cori A , Segreti L , Grifoni G , Fiorentini F , Torre M , Barletta V , Canu A , Sbragi S , Viani S , Tognetti A , Zucchelli G 
Published: May 2024

Abstract

Background
Catheter ablation is a cornerstone treatment for scar related post-infarction ventricular arrhythmias. Functional substrate driven ablation strategies guided by local activation time (LAT) mapping have been proven as efficient and effective approaches, especially when dealing with large scar areas. In-silico electrophysiological modeling is emerging as a potential tool for procedural planning and guidance.

Purpose
To clinically validate the feasibility, diagnostic performance, and accuracy of a novel late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) based digital twin framework for simulated LAT map generation in post-infarction patients and their integration with CARTO3 EAM suite.

Methods
Five ischemic subjects who underwent CMR-aided scar-related ventricular tachycardia ablation at our referral center were retrospectively enrolled. Their CMR derived 3D pixel-signal-intensity (PSI) maps generated with ADAS3D were processed with novel in-house software to obtain patient-specific ventricular geometry, tissue characterization, and to generate a model of Purkinje system and myocyte fiber orientation. According to local normalized pixel intensity (NPI) values, myocardial regions were marked as healthy, scar, or border-zone. Electrophysiological properties of border-zone (BZ) were modulated according to local NPI. Continuous and 8-steps isochronal endo-epicardial LAT maps were generated and imported in CARTO3 system, aligned with electroanatomical mapping (EAM), and compared at an ASE 17-segments level, in terms of sensitivity, specificity, predictive values, and accuracy to actual high-density LAT maps obtained with a multipolar catheter. Deceleration Zones (DZ) were defined as previously described (&gt;3 isochrones within 1 cm radius).

Results
A total of 85 ASE segments (34 epicardial) were analyzed. 24 EAM segments (28%) held DZs, 40 (47%) segments harbored bipolar scar or BZ. Thirty-seven (44%) CMR segments held scar core/BZ. Thirty (35%) digital model segments harbored DZs. Generated LAT maps were successfully imported and aligned with CARTO3 EAM suite for validation.
In terms of DZ localization prediction, our LAT model showed 83% sensitivity (95% CI 63%-95%), 90% specificity (95% CI 80%-96%), 77% positive predictive value (PPV) (95% CI 56%-91%), 93% negative predictive value (NPV) (95% CI 83%-98%), 88% accuracy (95% CI 79%-94%).

Conclusion
Our newly developed framework for LGE-CMR derived functional substrate simulation in post-infarction patients holds high sensitivity, specificity, predictive values, and accuracy for DZ localization. Further validation, with a larger sample size, is required for evaluating potential implications in clinical practice.
Using cardiac magnetic resonance feature tracking to discover novel abnormalities in patients with idiopathic ventricular fibrillation
Authors: Verheul L , Guglielmo M , Groeneveld S A , Prakken N H J , Velthuis B K , Hassink R J 
Published: May 2024

Abstract

Background
Despite an extensive diagnostic work-up, the underlying diagnosis leading to ventricular fibrillation (VF) remains elusive in patients with idiopathic VF. Emerging diagnostic techniques can be used to discover previously unidentified abnormalities in these patients.

Purpose
The purpose of this study was to investigate the potential of cardiac magnetic resonance feature tracking (CMR-FT) to discover structural abnormalities in idiopathic VF patients.

Methods
Cine CMR images of idiopathic VF patients and age and sex matched controls were analyzed. Left ventricle global circumferential strain (GCS), global longitudinal strain (GLS) and global radial strain (GRS) were determined using Circle Cardiovascular Imaging. Student’s t-test was used to compare means.

Results
In total, 26 idiopathic VF patients (mean age 37 (±13) years, 62% male) and 26 controls (mean age 38 (±13) years) were included. CMR was performed in idiopathic VF patients at a median of 9 [IQR 3 – 15] days after the index event. Left ventricle ejection fraction was 55 ± 6% for idiopathic VF patients, 59 ± 6% for controls, p = 0.04. GCS and GRS were comparable for idiopathic VF patients and controls (-17.36 ± 1.78% vs. -18.04 ± 1.83%, p = 0.182 and 28.28 ± 4.63 vs. 29.29 ± 5.09, p = 0.438, respectively). GLS was lower for idiopathic VF patients compared with controls (-14.85 ± 3.21% vs. -18.44 ± 2.11%, p &lt; 0.001).

Conclusion
CMR-FT GLS distinguished idiopathic VF patients from controls and could imply subclinical abnormalities in idiopathic VF patients. Future studies with a larger cohort should reveal if this finding can be correlated with an arrhythmic substrate.
Significance of Coherent Mapping in unveiling slow conduction zones of ventricular tachycardia substrate in ischemic cardiomyopathy
Authors: Yalin K , Ikitimur B , Soysal A U , Yalman H , Sanli S N , Baysal E , Bilge A K 
Published: May 2024

Abstract

Introduction
Ventricular tachycardia (VT) presents a formidable challenge, particularly in cases with extensive myocardial scar tissue, complicating critical ablation site identification. Prolonged interventions not only extend procedural durations but also heighten the risk of complications. This study aimed to assess the efficacy of coherent mapping techniques in precisely locating regions of slow conduction within scar tissue and explored potential correlations with electrophysiological markers in scar-related VT.

Methods
Seventeen patients (mean age: 61.6 ± 9.2 years, mean EF: 28 ± 9%) with ischemic cardiomyopathy (ICM) and frequent implantable cardioverter-defibrillator (ICD) shocks underwent high-density (&gt;2000 points) left ventricular (LV) substrate mapping (15 endo, 2 epicardial) during sinus or right ventricular (RV) pacing and ablation. Coherent mapping tool was utilized for the identification of slow conduction, demonstrated by vector thickening. Bipolar low voltage areas (LVAs) below 0.5 mV were defined as dense scar, and bipolar voltage between 0.5 and 1.5 mV was defined as the border zone (Figure, panel A). Late potentials (LPs) and local abnormal ventricular activities (LAVA) were manually identified and tagged. Isochronal late activation mapping (ILAM) was also performed to elucidate the functional properties of the substrate (Figure, Panel B).

Results
LPs and LAVA were identified in all cases, with a mean number of LPs being 10.0 ± 7.1. Of these, 14/17 cases had LPs located in dense scar, while 4/17 cases had LPs in the border zone. The mean area of LAVA was 9.9 ± 7.7 mm², located in dense scar in 6/17 cases and in the border zone in 15/17 cases. Average deceleration zones (DZ, &gt;3 isochrones in 1 cm radius) identified by ILAM was 2 ± 1. Coherent mapping consistently identified slow conduction zones adjacent to LVA in all cases, with these coherent map-based slow conduction zones (CM-SCZ) located in dense scar in 3/17 cases and in the border zone in 14/17 cases. The distance of CM-SCZ to LPs was 12.6 ± 13.9 mm (in 4 cases, LPs were recorded on the spot), and the distance to LAVAs was 18.8 ± 13.7 mm (in 2 cases, LAVAs were recorded on the spot). CM-SCZ was colocalized with DZ in 14/17 of the patients. Ablation lesions covered CM-SCZ in 10/17 cases. Over a mean follow-up duration of 11 ± 6.5 months, 4 patients experienced VT recurrence, with 3 having no ablation lesions covering CM-SCZ, and 2 patients died due to pump failure.

Conclusion
This study underscores the significance of coherent mapping in refining the understanding of VT substrate in ICM. Identifying and ablating CM-SCZ during substrate-based mapping may provide a potential additional benefit for VT ablation. Nevertheless, larger studies are needed to clarify the prognostic significance and validate the clinical benefits of this approach.Figure 1