Machine learning identifies esophageal luminal temperature patterns associated with thermal injury in catheter ablation for atrial fibrillation.

INTRODUCTION: Luminal esophageal temperature (LET) monitoring during atrial fibrillation (AF) ablation is widely used to reduce the incidence of endoscopically detected esophageal lesion (EDEL). We sought to assess whether specific patterns of LET variation are associated with EDEL. METHODS: A high-fidelity multisensor probe was used to record LET in AF patients undergoing radiofrequency ablation (RFA) or cryoballoon ablation (CBA). Explainable machine learning and SHapley Additive exPlanations (SHAP) analysis were used to predict EDEL and assess feature importance. RESULTS: A total of 94 patients (38.3% persistent AF, 71.3% male, 72 RFA, and 22 CBA) were included. EDEL was detected in 11 patients (10 RFA and one CBA). In the RFA group, the highest LET recorded was similar between patients with and without EDEL (40.6 [40.1-41]°C vs. 40.2 [39.1-40.9]°C; p = .313), however, the rate of LET rise for the highest recorded peak was higher (0.08 [0.03-0.12]°C/s vs. 0.02 [0.01-0.05]°C/s; p = .033), and the area under the curve (AUC) for the highest peak was smaller (412.5 [206.8-634.1] vs. 588.6 [380.4-861.1]; p = .047) in patients who had EDEL. In case of CBA, the patient with EDEL had a faster LET decline (0.12 vs. 0.07 [0.02-0.14]°C/s), and a smaller AUC for the lowest trough (2491.3 vs. 2629.3 [1712.6-5283.2]). SHAP analysis revealed that a rate of LET change higher than 0.05°C/s and an AUC less than 600 were more predictive of EDEL in RFA. CONCLUSION: The rate of LET change and AUC for the recorded temperature predicted EDEL, whereas absolute peak temperatures did not.

Pathology of breast cancer metastasis and a view of metastasis to the brain.

Despite the advances in diagnosis and management of breast cancer, metastasis has been responsible for the staggering percentage of breast cancer-related death. Mortality threat can be explained mostly by the lack of proper understanding of the diversity of pathological features and underlying mechanism of breast cancer metastasis and effective targeted therapy. Breast cancer stem cells (BCSCs) are the potential source of tumor cells spread to distant organs. BCSCs targeted therapy can suppress the breast cancer progression to metastasis. Spreading of tumor cells to the bone, lung, liver, and brain occurs through a distinct non-random process; called metastasis organotropism. Recently, brain metastasis in breast cancer patients has been detected more frequently, causing a significant clinical burden. BRCA1 and BRCA2 associated breast cancers carry a remarkably higher propensity of CNS metastasis. BRCA1 and BRCA2 associated breast cancers commonly have the propensity to be the triple-negative (TN) and hormone receptors (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative molecular subtypes, respectively. Regardless of molecular subtypes, metastasis is most commonly evident at the bone. Heterogeneity is a critical pathological feature, leads to therapeutic resistance. BCSCs, biomarkers expression patterns, and mutations contribute to heterogeneity. In this paper, we discuss crucial pathological features of breast cancer metastasis, emphasizing metastasis organotropism and heterogeneity; and mechanisms of breast cancer metastasis, highlighting the pathways of metastasis to the brain. We consider that this paper reinforces future research areas and benefits the general readers, physicians, and researchers to identify potential areas to develop targeted therapies.

Cryoballoon temperature parameters during cryoballoon ablation predict pulmonary vein reconnection and atrial fibrillation recurrence.

BACKGROUND: Cryoballoon ablation (CBA) is an established approach for rhythm management of atrial fibrillation (AF). We sought to assess balloon temperature (BT) parameters as predictors of pulmonary vein (PV) reconnection within the index procedure and AF recurrence following CBA. METHODS: BT was monitored in 119 AF patients undergoing CBA. PVs were assessed for reconnection during the procedure and patients were followed for arrhythmia recurrence. RESULTS: PV reconnection was identified in 39 (8.3%) of 471 PVs. BT was significantly colder in the absence of PV reconnection (30 s: - 33.5 °C [- 36; - 30] vs - 29.5 °C [- 35; - 25.5], p = 0.001; 60 s: - 41 °C [- 44; - 37] vs - 36.5 °C [- 42; - 33.5], p < 0.001; nadir: - 47 °C [- 52; - 43] vs - 41.5 °C [- 47; - 38], p < 0.001). PV reconnection was associated with significantly longer time to reach - 15 °C and - 40 °C (14.5 s [11.5-18.5] vs 12 s [10-15.5], p = 0.023; and 75 s [40-95.5] vs 46 s [37-66.75], p = 0.005) and shorter rewarming time (5.75 s [4.75-8.5] vs 7 s [6-9], p = 0.012). ROC analysis of these procedural parameters had an AUC = 0.71 in predicting PV reconnection. AF recurrence occurred in 51 (42.8%) patients. Kaplan-Meier analysis showed better arrhythmia-free survival for patients in whom BT decreased below - 40 °C in all PVs and patients who had no early PV reconnections, compared to patients in whom BT below - 40 °C was not achieved in at least one PV (log rank = 6.3, p = 0.012) and patients who had PV reconnections (log rank = 4.1, p = 0.043). CONCLUSIONS: Slower BT decline, warmer BT nadir, and faster rewarming time predict early PV reconnection. Absence of early PV reconnections and BT dropping below - 40 °C in all PVs during CBA are associated with lower rates of AF recurrence.

Comparing Inducibility of Re-Entrant Arrhythmia in Patient-Specific Computational Models to Clinical Atrial Fibrillation Phenotypes.

BACKGROUND: Computational models of fibrosis-mediated, re-entrant left atrial (LA) arrhythmia can identify possible substrate for persistent atrial fibrillation (AF) ablation. Contemporary models use a 1-size-fits-all approach to represent electrophysiological properties, limiting agreement between simulations and patient outcomes. OBJECTIVES: The goal of this study was to test the hypothesis that conduction velocity (Ï´) modulation in persistent AF models can improve simulation agreement with clinical arrhythmias. METHODS: Patients with persistent AF (n = 37) underwent ablation and were followed up for ≥2 years to determine post-ablation outcomes: AF, atrial flutter (AFL), or no recurrence. Patient-specific LA models (n = 74) were constructed using pre-ablation and ≥90 days' post-ablation magnetic resonance imaging data. Simulated pacing gauged in silico arrhythmia inducibility due to AF-like rotors or AFL-like macro re-entrant tachycardias. A physiologically plausible range of Ï´ values (±10 or 20% vs. baseline) was tested, and model/clinical agreement was assessed. RESULTS: Fifteen (41%) patients had a recurrence with AF and 6 (16%) with AFL. Arrhythmia was induced in 1,078 of 5,550 simulations. Using baseline Ï´, model/clinical agreement was 46% (34 of 74 models), improving to 65% (48 of 74) when any possible Ï´ value was used (McNemar's test, P = 0.014). Ï´ modulation improved model/clinical agreement in both pre-ablation and post-ablation models. Pre-ablation model/clinical agreement was significantly greater for patients with extensive LA fibrosis (>17.2%) and an elevated body mass index (>32.0 kg/m2). CONCLUSIONS: Simulations in persistent AF models show a 41% relative improvement in model/clinical agreement when Ï´ is modulated. Patient-specific calibration of Ï´ values could improve model/clinical agreement and model usefulness, especially in patients with higher body mass index or LA fibrosis burden. This could ultimately facilitate better personalized modeling, with immediate clinical implications.

Esophageal luminal temperature monitoring using a multi-sensor probe lowers the risk of esophageal injury in cryo and radiofrequency catheter ablation for atrial fibrillation.

BACKGROUND: Esophageal luminal temperature monitoring is a commonly used strategy to reduce esophageal thermal injury in catheter ablation for atrial fibrillation (AFib). OBJECTIVES: We sought to compare the incidence of endoscopically detected esophageal lesions (EDEL) between two commonly used esophageal luminal temperature probes. METHODS: Consecutive patients undergoing ablation with esophageal luminal temperature monitoring and upper endoscopy within 24 h after ablation were included. RESULTS: Four hundred forty-five patients (64 ± 10 years, 44% female) were included. Esophageal temperature monitoring was done with a single-sensor probe in 213 (48%) and multi-sensor probe in 232 (52%). Cryoballoon (CB) ablation was performed in 118 (27%) and radiofrequency (RF) ablation in 327 (73%) of patients. EDEL was present in 94 (22.9%) of which 85 were mild, 8 were moderate, and 1 was severe, and none progressed to atrial-esophageal fistula. The use of the multi-sensor probe during CB ablation was associated with a reduction in EDEL compared to single sensor (6.8% vs 24.3%; P = 0.016). Similarly, in the RF ablation group, EDEL was present in 19.5% of the multi-sensor group vs 32.8% in the single-sensor group (P = 0.001). Logistic regression showed that multi-sensor probe use was associated with reduction in EDEL with an odds ratio of 0.23 in CB ablation (P = 0.024) and 0.44 for RF ablation (P = 0.001). CONCLUSIONS: Esophageal luminal temperature monitoring during AFib ablation using a multi-sensor probe was associated with a significant reduction in EDEL compared to a single-sensor probe.

Epicardial adipose tissue is associated with left atrial volume and fibrosis in patients with atrial fibrillation.

Background: Obesity is a risk factor for atrial fibrillation (AF) and strongly influences the response to treatment. Atrial fibrosis shows similar associations. Epicardial adipose tissue (EAT) may be a link between these associations. We sought to assess whether EAT is associated with body mass index (BMI), left atrial (LA) fibrosis and volume. Methods: LA fibrosis and EAT were assessed using late gadolinium enhancement, and Dixon MRI sequences, respectively. We derived 3D models incorporating fibrosis and EAT, then measured the distance of fibrotic and non-fibrotic areas to the nearest EAT to assess spatial colocalization. Results: One hundred and three AF patients (64% paroxysmal, 27% female) were analyzed. LA volume index was 54.9 (41.2, 69.7) mL/m2, LA EAT index was 17.4 (12.7, 22.9) mL/m2, and LA fibrosis was 17.1 (12.4, 23.1)%. LA EAT was significantly correlated with BMI (R = 0.557, p < 0.001); as well as with LA volume and LA fibrosis after BSA adjustment (R = 0.579 and R = 0.432, respectively, p < 0.001 for both). Multivariable analysis showed LA EAT to be independently associated with LA volume and fibrosis. 3D registration of fat and fibrosis around the LA showed no clear spatial overlap between EAT and fibrotic LA regions. Conclusion: LA EAT is associated with obesity (BMI) as well as LA volume and fibrosis. Regions of LA EAT did not colocalize with fibrotic areas, suggesting a systemic or paracrine mechanism rather than EAT infiltration of fibrotic areas.

Mediterranean Diet and Physical Activity: Two Imperative Components in Breast Cancer Prevention.

Despite tremendous advances in medicine over the past few decades and significantly improved understanding of the symptomology and contributors to breast cancer (BC) incidence, BC rates continue to rise worldwide, with BC being a leading cause of cancer-related death among women. To reduce BC incidence, it is necessary to focus on promoting prevention strategies through a population-based approach of lowering exposure to modifiable risk factors in addition to the application of newer drug interventions (chemoprevention) for prevention in high-risk populations. Currently, available data suggest that lifestyle modifications through a healthy diet and increased physical activity (PA) play a crucial role in BC prevention; specifically, there is growing evidence to indicate that the Mediterranean diet (MeD) lowers cancer risk. This review summarizes the potential role of the MeD and PA in reducing BC risk, with an additional focus on microbial modulation in BC prevention, based on the current evidence obtained from PubMed. After reviewing the immunomodulatory and anticarcinogenic effects of both the MeD and PA, we conclude that further evaluation and proper implementation of both interventions can significantly reduce the risk of BC and associated mortality in the general population.