Abstract
Funding Acknowledgements
Type of funding sources: None.
Background
To evaluate myocardial injury in Atrial Fibrillation (AF) patients undergoing High Power Short Duration radiofrequency ...(HPSD) and visually guided Laser Balloon Ablation (LBA).
Methods and results
In this single center registry we prospectively enrolled 40 patients (67% male), mean age 63±9, with paroxysmal or persistent AF (see table I). The ablation target has been the pulmonary vein isolation (PVI) with LBA and wide area circumferential ablation (WACA) with HPSD.
6 and 18 hours post-procedure samples of high sensitive cardiac troponin I (cTnI) were collected.
The results show not significant differences in target population and no significant differences in high sensitive cardiac troponin I (cTnI pg/ml) levels at 6h (HPSD cTnI =806±496 pg/ml vs laser cTnI = 664±339 pg/ml p=0.17) and 18 hours after ablation (HPSD cTnI =833±540 pg/ml vs laser cTnI = 1081±962 pg/ml p=0.07).
Conclusion
These results indicate that myocardial injury induced by HPSD and LBA at 6 and 18 hours after procedure are similar targeting WACA and PVI respectively. This registry is ongoing to evaluate freedom from AF at 12 months follow up.
Abstract Introduction In individuals with Brugada syndrome, the presence of the type 1 pattern (BP1) is linked to an elevated risk of severe arrhythmias. However, the identification and measurement ...of BP1 can be challenging due to its intermittent nature. Implantable cardiac monitors (ICMs) provide extended continuous monitoring, potentially overcoming the limitations of intermittent ambulatory ECG monitoring in detecting spontaneous BP1. Nevertheless, their specific application for this purpose remains unevaluated. Methods From November 2022 to September 2023, all patients presenting with pharmacologically induced BP1 were enrolled at our centre. An ICM was surgically placed in the left second intercostal space at a 45° angle, enabling readings with a morphology similar to the right precordial ECG leads during ajmaline testing (AT). Patients were remotely monitored, and in addition to routine automatic transmissions, each patient was provided with a remote control to transmit in case of fever or symptomatic events. Transmissions were scrutinized to detect: 1) ST-segment elevation; 2) ventricular arrhythmias; 3) burden of ventricular extrasystoles (PVC). A reading was classified as positive for BP1 if it bore a similar morphology to that recorded during AT. The frequency of BP1-positive transmissions was evaluated across four hourly intervals. Results The ICM was successfully implanted in 21 patients (male-to-female ratio 1.62:1, mean age 43.9±13.1 years). Over an average follow-up of 168±70.6 days, a total of 7818 transmissions were received, evenly spread across hourly intervals (minimum of 1296 transmissions per interval). Among these, 173 transmissions were identified as BP1 positive (2.2%), originating from 6 patients (28.6% of the total, all newly diagnosed with spontaneous BP1). The median duration between implantation and the diagnosis of spontaneous BP1 was 16.5 days (range 2-23). The median number of days with at least one positive transmission was 30.2 (range 13.4-73.9). The evening period (6 pm to midnight) displayed a significantly higher rate of positive transmissions compared to the morning (p=0.04) and afternoon (p=0.01); however, not in contrast to the nighttime (p=0.8). No sustained ventricular arrhythmias were observed, and there were no significant differences in PVC burden among patients. Conclusions The utilization of ICM for continuous monitoring in patients with pharmacologically induced BP1 led to the identification of spontaneous BP1 patterns in almost 30% of cases during an approximately 6-month follow-up. Evening and nighttime periods exhibited the highest incidence of BP1. This methodology shows promise in quantifying BP1 incidence and could serve as a tool for stratifying arrhythmic risk in individuals with Brugada syndrome.
Abstract Introduction The presence of spontaneous type 1 Brugada pattern (BP1) is associated with an elevated risk of arrhythmic events. Diagnosis of this condition is often underestimated due to its ...intermittent nature. While periodic ambulatory ECG monitoring can distinguish patients with pharmacologically induced patterns from those with spontaneous patterns, the diagnostic capabilities of this method are limited. Implantable cardiac monitors (ICM), designed to continuously record heart rhythm, may offer higher sensitivity in detecting patients with intermittent patterns. However, the ICM's ability to morphologically identify the ST segment elevation associated with BP1 remains uncharted. Purpose This study aimed to assess the ICM's capacity to morphologically identify the ST segment elevation associated with BP1. Methods We enrolled all patients who underwent ajmaline testing (AT) between November 2022 and September 2023 in our centre. For positive patients, the external simulator of a loop recorder was utilized to evaluate four positions (I-II left intercostal space at a 45° tilt, II-III left intercostal space at a 45° tilt, II-III right parasternal intercostal space, and II-III left parasternal intercostal space). These positions were selected to capture the trace with the most significant ST segment elevation at the J point during the peak positivity of the ECG during the ajmaline test. Measurements from the recorded traces were acquired using dedicated software. Results Out of 50 patients, 21 (male-to-female ratio 1.62:1, mean age 43.4±13.1 years) had a positive AT result. Seventeen patients exhibited ST segment elevation in the simulator trace during the highest ajmaline dose. Among these patients, the optimal recording position was in the I-II left intercostal space at a 45° tilt in 66.7% of cases. The median ST segment elevation recorded by the simulator was 0.9 mm (interquartile range 0.6-1.1 mm). Notably, there was no observed correlation between the extent of ST segment elevation in the ECG and that recorded by the simulator trace (Pearson linear coefficient = 0.09). Conclusions ICM may offer the potential to record BP1, a finding that holds significant diagnostic and prognostic implications for asymptomatic patients with pharmacologically induced BP1. Further research is needed to develop useful programming algorithms for the automatic recording of this pattern.
Somatic copy number alterations (SCNAs) are pervasive in advanced human cancers, but their prevalence and spatial distribution in early-stage, localized tumors and their surrounding normal tissues ...are poorly characterized. Here, we perform multi-region, single-cell DNA sequencing to characterize the SCNA landscape across tumor-rich and normal tissue in two male patients with localized prostate cancer. We identify two distinct karyotypes: 'pseudo-diploid' cells harboring few SCNAs and highly aneuploid cells. Pseudo-diploid cells form numerous small-sized subclones ranging from highly spatially localized to broadly spread subclones. In contrast, aneuploid cells do not form subclones and are detected throughout the prostate, including normal tissue regions. Highly localized pseudo-diploid subclones are confined within tumor-rich regions and carry deletions in multiple tumor-suppressor genes. Our study reveals that SCNAs are widespread in normal and tumor regions across the prostate in localized prostate cancer patients and suggests that a subset of pseudo-diploid cells drive tumorigenesis in the aging prostate.
Background The "HER2-low" nomenclature identifies breast carcinomas (BCs) displaying a HER2 score of 1+/2+ in immunohistochemistry and lacking ERBB2 amplification. Whether HER2-low BCs (HLBCs) ...constitute a distinct entity is debated. Methods We performed DNA and RNA high-throughput analysis on 99 HLBC samples (n = 34 cases with HER2 score 1+/HLBC-1, n = 15 cases with HER2 score 2+ and ERBB2 not amplified/HLBC-2N, and n = 50 cases with score 2+ and ERBB2 copy number in the equivocal range/HLBC-2E). We compared the mutation rates with data from 1317 samples in the Memorial Sloan-Kettering Cancer Center (MSKCC) BC cohort and gene expression data with those from an internal cohort of HER2-negative and HER2-positive BCs. Results The most represented mutations affected PIK3CA (31/99, 31%), GATA3 (18/99, 18%), TP53 (17/99, 17%), and ERBB2 (8/99, 8%, private to HLBC-2E). Tumor mutational burden was significantly higher in HLBC-1 compared to HLBC-2E/N (P = 0.04). Comparison of mutation spectra revealed that HLBCs were different from both HER2-negative and HER2-positive BCs, with HLBC-1 resembling more HER2-negative tumors and HLBC-2 mutationally related to HER2-addicted tumors. Potentially actionable alterations (annotated by using OncoKB/ESCAT classes) affected 52 patients. Intra-group gene expression revealed overlapping features between HLBC-1 and control HER2-negative BCs, whereas the HLBC-2E tumors showed the highest diversity overall. The RNA-based class discovery analysis unveiled four subsets of tumors with (i) lymphocyte activation, (ii) unique enrichment in HER2-related features, (iii) stromal remodeling alterations, and (iv) actionability of PIK3CA mutations (LAURA classification). Conclusions HLBCs harbor distinct genomic features when compared with HER2-positive and HER2-negative BCs; however, differences across IHC classes were also unveiled thus dissecting the full picture of heterogeneity across HER2-low disease. The HLBC-2E category harbors most distinctive features, whereas HLBC-1 seems superimposable to HER2-negative disease. Further studies are needed to ascertain whether the four genomic-driver classes of the LAURA classification hold prognostic and/or predictive implications. Keywords: Breast cancer, HER2, HER2-low, Heterogeneity, Classification, Mutation, Actionable alteration, Gene expression, Transcriptome, Stratification
Abstract
Background
Laser balloon ablation is a promising option for performing pulmonary vein isolation (PVI) which is the cornerstone of invasive atrial fibrillation (AF) treatment.
Purpose
We ...aimed to investigate the acute efficacy and safety of the novel third-generation of the laser balloon system in an initial multicenter experience.
Methods
First and consecutive patients who underwent PVI with LB3 for drug-resistant paroxysmal or persistent AF at 7 Italian sites were included in this analysis. Study endpoints were acute procedural efficacy, defined as successful isolation of all identified PVs without radiofrequency touch-up, total and fluoroscopy times, and periprocedural complications.
Results
Our population included 86 patients (81% males, mean age 60.6±9.5 years) who underwent a procedure of PVI using LB3 between June 2020 and March 2021.
Most patients had paroxysmal AF (74%) and were in sinus rhythm at the beginning of the procedure. The mean procedure time was 138±60 min; fluoroscopy time was 22±17 min and the mean ablation time was 44±40 min. Of the 313 targeted PVs, 311 (99.4%) could be isolated with first-pass LB3 application, while 2 (0.6%) required radiofrequency touchup. At the end of the procedure, all patients were in sinus rhythm and 26 (32%) received electrical cardioversion to achieve stable sinus rhythm.
The total rate of major compilations was 1.2% (1/82 patients): one pericardial tamponade requiring epicardial puncture. No surgical intervention was necessary, and the patient recovered without any sequalae. There were no vascular access complications or phrenic nervy palsy. Three pinhole balloon raptures (3.5%) were observed during energy applications that required replacement of the whole system but had no effect on patient safety.
Conclusions
In a first multicenter experience, the LB3 system for PVI was safe with excellent acute efficacy.
Funding Acknowledgement
Type of funding sources: None.
Abstract
Background
Automatic diagnosis of implantable cardioverter defibrillator (ICD) requires confirmation through analysis of electrograms (EGM) recordings by an electrophysiologist (EP) ...specialist.
Purpose
To investigate whether the atrial sensing capability in single-chamber ICD improves reliability in episodes assessment.
Methods
The THINGS registry enrolled 526 consecutive patients without atrial pacing indication who underwent single-lead ICD implantation. Of them, 343 patients received a conventional single-chamber ICD (ICD VR) and 183 a single-lead ICD with atrial sensing capability (ICD DX, BIOTRONIK). Device-detected ventricular episodes were independently classified by two experienced electrophysiologists as ventricular (VT) or supraventricular tachycardia (SVT) by analyzing the EGMs. In case of disagreement, a third experienced EP specialist, blinded to previous assessment, was consulted. The inter-rate reliability was evaluated using the Cohen's kappa (k) coefficient in the ICD VR and ICD DX group.
Results
A total 441 (383 in the ICD VR and 58 in the ICD DX group) device-detected events were analyzed. Using ventricular EGM alone for ICD VR patients, the proportion of observed agreement between the 1st and 2nd adjudicator was 86.4% consisting of 268 (70.0%) episodes confirmed as VT and 63 (16.4%) classified as SVT. The k coefficient was 0.61 and no agreement was reached for 52 (13.6%) tracings. For them, the third assessment had low agreement with both previous EP evaluations (the k coefficients 1st/3th and 2nd/3th EP specialist were 0.03 and −0.05, respectively).
In ICD DX group, with available atrial EGM, the proportion of observed agreement in the first stage improved to 93.0%: 44 (75.8%) episodes were adjudicated as VT and 10 (17.2%) as SVT with a k=0.79. Only 4 (7.0%) recordings had a discordant classification. For them, the 2nd and 3rd EP specialist had perfect agreement (k=1).
Conclusions
Atrial sensing capability improves EP specialist assessment of ICD episodes allowing dual EGMs analysis. Misinterpretation of ICD recordings may thus be less common in ICD DX than in conventional single-chamber ICD VR and may improve clinical decisions.
Funding Acknowledgement
Type of funding sources: None.
Abstract Many computer studies and models have been developed in order to simulate cell biochemical pathways. The difficulty of integrating all the biochemical reactions that occur in a cell in a ...single model is the main reason for the poor results in the prediction and simulation of cell behaviour under different chemical and physical stimuli. In this paper we have translated biochemical reactions into differential equations for the development of modular model of metabolism of a hepatocyte cultured in static and standard conditions (in a plastic multiwell placed in an incubator at 37 °C with 5% of CO2 ). Using biochemical equations and energetic considerations a set of non-linear differential equations has been derived and implemented in Simulink® . This set of equations mimics some of the principal metabolic pathways of biomolecules present in the culture medium. The software platform developed is subdivided into separate modules, each one describing a different metabolic pathway; they constitute a library which can be used for developing new modules and models to project, predict and validate cell behaviour in vitro.
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