Os Biomarcadores podem ser Utilizados para Prever Recorrência de Arritmia após a Ablação de Fibrilação Atrial Guiada pelo Ablation-Index? / Can Pre-Ablation Biomarkers Be Used to Predict Arrhythmia Recurrence after Ablation Index-Guided Atrial Fibrillation Ablation?

Resumo Fundamento: O software ablation index (AI) permitiu melhorar os resultados da ablação de fibrilação atrial (FA), mas as taxas de recorrência permanecem significativas. Biomarcadores séricos específicos têm sido associados a essa recorrência. Objetivos: Avaliar se certos biomarcadores podem ser utilizados (individualmente ou combinados) para predizer a recorrência de FA pós ablação guiada pelo AI. Métodos: Estudo multicêntrico, observacional, prospectivo de pacientes consecutivos, encaminhados para ablação de FA de janeiro de 2018 a março de 2021. Hemoglobina, peptídeo natriurético cerebral (BNP), proteína C reativa, troponina I ultrassensível, clearance de creatinina, Hormônio Tireoestimulante (TSH), e Tiroxina livre (T4) foram avaliados quanto à capacidade de prever a recorrência de arritmias durante o acompanhamento. Valores de p <0,05 foram aceitos como estatisticamente significativos. Resultados: Um total de 593 pacientes foram incluídos - 412 com FA paroxística e 181 com FA persistente. Durante o seguimento médio de 24±6 meses, 76,4% não apresentaram recidiva após ablação. Individualmente, os biomarcadores demonstraram um valor preditivo baixo ou nulo para recorrência. No entanto, TSH >1,8 μUI/mL [HR=1,82 (IC95%, 1,89-2,80), p=0,006] foi um preditor independente de recorrência. Avaliando-se a combinação de TSH, FT4 e BNP, a adição de cada valor "anormal" foi associada a uma menor sobrevida livre de recorrência (87,1% se nenhum vs. 83,5% se um vs. 75,1% se dois vs. 43,3% se três biomarcadores, p<0,001). Doentes com três biomarcadores "anormais" apresentaram três vezes maior probabilidade de recorrência de FA, comparativamente aos que não apresentaram nenhum biomarcador "anormal" (HR=2,88 [IC95%, 1,39-5,17], p=0,003). Conclusões: Quando combinados, valores anormais de TSH, FT4 e BNP podem ser uma ferramenta útil para prever a recorrência de FA pós ablação guiada pelo AI.

Abstract Background: Ablation Index (AI) software has allowed better atrial fibrillation (AF) ablation results, but recurrence rates remain significant. Specific serum biomarkers have been associated with this recurrence. Objectives: To evaluate whether certain biomarkers could be used (either individually or combined) to predict arrhythmia recurrence after AI-guided AF ablation. Methods: Prospective multicenter observational study of consecutive patients referred for AF ablation from January 2018 to March 2021. Hemoglobin, brain natriuretic peptide (BNP), C-reactive protein, high sensitivity cardiac troponin I, creatinine clearance, thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were assessed for their ability to predict arrhythmia recurrence during follow-up. Statistical significance was accepted for p values of<0.05. Results: A total of 593 patients were included - 412 patients with paroxysmal AF and 181 with persistent AF. After a mean follow-up of 24±6 months, overall single-procedure freedom from atrial arrhythmia was 76.4%. Individually, all biomarkers had no or only modest predictive power for recurrence. However, a TSH value >1.8 μUI/mL (HR=1.82 [95% CI, 1.89-2.80], p=0.006) was an independent predictor of arrhythmia recurrence. When assessing TSH, FT4 and BNP values in combination, each additional "abnormal" biomarker value was associated with a lower freedom from arrhythmia recurrence (87.1 % for no biomarker vs. 83.5% for one vs. 75.1% for two vs. 43.3% for three biomarkers, p<0.001). Patients with three "abnormal" biomarkers had a threefold higher risk of AF recurrence compared with no "abnormal" biomarker (HR=2.88 [95% CI, 1.39-5.17], p=0.003). Conclusions: When used in combination, abnormal TSH, FT4 and BNP values can be a useful tool for predicting arrhythmia recurrence after AI-guided AF ablation.

Clinical factors influencing long-term survival in a real-life cohort of early stage non-small-cell lung cancer patients in Spain.

Background: Current prognosis in oncology is reduced to the tumour stage and performance status, leaving out many other factors that may impact the patient´s management. Prognostic stratification of early stage non-small-cell lung cancer (NSCLC) patients with poor prognosis after surgery is of considerable clinical relevance. The objective of this study was to identify clinical factors associated with long-term overall survival in a real-life cohort of patients with stage I-II NSCLC and develop a prognostic model that identifies features associated with poor prognosis and stratifies patients by risk. Methods: This is a cohort study including 505 patients, diagnosed with stage I-II NSCLC, who underwent curative surgical procedures at a tertiary hospital in Madrid, Spain. Results: Median OS (in months) was 63.7 (95% CI, 58.7-68.7) for the whole cohort, 62.4 in patients submitted to surgery and 65 in patients submitted to surgery and adjuvant treatment. The univariate analysis estimated that a female diagnosed with NSCLC has a 0.967 (95% CI 0.936 - 0.999) probability of survival one year after diagnosis and a 0.784 (95% CI 0.712 - 0.863) five years after diagnosis. For males, these probabilities drop to 0.904 (95% CI 0.875 - 0.934) and 0.613 (95% CI 0.566 - 0.665), respectively. Multivariable analysis shows that sex, age at diagnosis, type of treatment, ECOG-PS, and stage are statistically significant variables (p<0.10). According to the Cox regression model, age over 50, ECOG-PS 1 or 2, and stage ll are risk factors for survival (HR>1) while adjuvant chemotherapy is a good prognostic variable (HR<1). The prognostic model identified a high-risk profile defined by males over 71 years old, former smokers, treated with surgery, ECOG-PS 2. Conclusions: The results of the present study found that, overall, adjuvant chemotherapy was associated with the best long-term OS in patients with resected NSCLC. Age, stage and ECOG-PS were also significant factors to take into account when making decisions regarding adjuvant therapy.

High-power short-duration versus low-power long-duration ablation guided by the ablation index.

AIMS: To compare the two different ablation strategies, both guided by the Ablation Index (AI), in the setting of atrial fibrillation (AF) ablation: high-power short-duration (HPSD) ablation using 40 W on the posterior wall and 50 W elsewhere versus low-power long-duration (LPLD) using 25 W posteriorly and 35 W elsewhere. METHODS: Prospective, multicenter nonrandomized, noninferiority study of consecutive patients referred for paroxysmal AF ablation from January 2018 to July 2019. Ablation was guided by the AI (≥500 for anterior segments, ≥450 for the roof and inferior segments and 400 posteriorly) and an interlesion distance (ILD) ≤ 6 mm. Patients were separated into two groups: HPSD vs LPLD. Acute reconnection (after adenosine trial) and 2-year outcomes were assessed. RESULTS: 160 patients (61% males, median age of 62 [IQR 51-69] years), fulfilled the study inclusion criteria - 80 patients (316 pulmonary veins [PV]) in the HPSD group and 80 patients (314 PV) in the LPLD. The probability of acute PV reconnection was similar between both groups: 2.2% in HPSD, 95%CI 0.6% to 3.8% vs. 3.4% in LPLD, 95%CI 1.4% to 5.4%; p < 0.001 for noninferiority. Median PV ablation time (20 min vs 30 min, p < 0.01) and procedure duration (80 min vs 100 min, p < 0.001) were shorter in the HPSD group. After a median follow-up of 26 months, arrhythmia recurrence was similar between groups (17.5% in HPSD group vs. 18.8% in LPLD group, p = 0.79). CONCLUSIONS: In paroxysmal AF patients treated with the Ablation Index, a HPSD strategy is noninferior to the more standard LPLD ablation, while allowing for quicker procedures with shorter ablation times.

Assessing the risk of cardiovascular events in patients receiving immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, despite their excellent therapeutic effect, these medications typically result in a broad spectrum of toxicity reactions. Immune-related cardiotoxicity is uncommon but can be potentially fatal, and its true incidence is underestimated in clinical trials. The aim of this study is to assess the incidence and identify risk factors for developing a cardiac event in patients treated with ICIs. Methods: We conducted a single-institution retrospective study, including patients treated with ICIs in our center. The main outcomes were cardiac events (CE) and cardiovascular death. Results: A total of 378 patients were analyzed. The incidence of CE was 16.7%, during a median follow-up of 50.5 months. The multivariable analysis showed that age, a history of arrhythmia or ischemic heart disease, and prior immune-related adverse events were significantly associated with CE. Conclusion: CE during ICI treatment are more common than currently appreciated. A complete initial cardiovascular evaluation is recommended, especially in high-risk patients, being necessary a multidisciplinary approach of a specialized cardio-oncology team.

An Artificial Intelligence-Based Tool for Data Analysis and Prognosis in Cancer Patients: Results from the Clarify Study.

BACKGROUND: Artificial intelligence (AI) has contributed substantially in recent years to the resolution of different biomedical problems, including cancer. However, AI tools with significant and widespread impact in oncology remain scarce. The goal of this study is to present an AI-based solution tool for cancer patients data analysis that assists clinicians in identifying the clinical factors associated with poor prognosis, relapse and survival, and to develop a prognostic model that stratifies patients by risk. MATERIALS AND METHODS: We used clinical data from 5275 patients diagnosed with non-small cell lung cancer, breast cancer, and non-Hodgkin lymphoma at Hospital Universitario Puerta de Hierro-Majadahonda. Accessible clinical parameters measured with a wearable device and quality of life questionnaires data were also collected. RESULTS: Using an AI-tool, data from 5275 cancer patients were analyzed, integrating clinical data, questionnaires data, and data collected from wearable devices. Descriptive analyses were performed in order to explore the patients' characteristics, survival probabilities were calculated, and a prognostic model identified low and high-risk profile patients. CONCLUSION: Overall, the reconstruction of the population's risk profile for the cancer-specific predictive model was achieved and proved useful in clinical practice using artificial intelligence. It has potential application in clinical settings to improve risk stratification, early detection, and surveillance management of cancer patients.

Two years after pulmonary vein isolation guided by ablation index-a multicenter study.

Background: The use of the Ablation Index (AI) software for paroxysmal atrial fibrillation (AF) has been associated with higher acute effectiveness and higher 1-year arrhythmia freedom. There is, however, a lack of data concerning longer follow-up. We aim to evaluate the 2-year outcomes after a standardized AI-guided pulmonary vein isolation (PVI). Methods: Prospective, multicenter study of consecutive patients referred for paroxysmal AF ablation from January 2018 to July 2019. PVI was guided by a tailored AI value (≥500 for anterior segment, ≥450 for the roof segments and inferior segments, and 400 for the posterior wall) and an ILD ≤6 mm. The primary endpoints were acute and long-term effectiveness. Results: The study included 218 (842 PV) patients (61% males, median age of 60 [IQR 49-68] years) with paroxysmal AF. First-pass isolation was obtained in 93% of the patients, with an acute reconnection occurring in 10.6% of the patients (3.2% of the PV) following adenosine trial. After a median follow-up of 26 (IQR 20-30) months, freedom from any documented atrial arrhythmia was 83.4%, off-AAD. The rate of adverse events was 1.4%. Although procedural parameters differ across centers (p < 0.001), the acute (p = 0.56) and long-term effectiveness (p = 0.83) were consistent between centers. Conclusions: Patients with paroxysmal AF submitted to an AI-guided PVI workflow presented high arrhythmia freedom at 2-years of follow-up.

Determination of essential biomarkers in lung cancer: a real-world data study in Spain with demographic, clinical, epidemiological and pathological characteristics.

BACKGROUND: The survival of patients with lung cancer has substantially increased in the last decade by about 15%. This increase is, basically, due to targeted therapies available for advanced stages and the emergence of immunotherapy itself. This work aims to study the situation of biomarker testing in Spain. PATIENTS AND METHODS: The Thoracic Tumours Registry (TTR) is an observational, prospective, registry-based study that included patients diagnosed with lung cancer and other thoracic tumours, from September 2016 to 2020. This TTR study was sponsored by the Spanish Lung Cancer Group (GECP) Foundation, an independent, scientific, multidisciplinary oncology society that coordinates more than 550 experts and 182 hospitals across the Spanish territory. RESULTS: Nine thousand two hundred thirty-nine patients diagnosed with stage IV non-small cell lung cancer (NSCLC) between 2106 and 2020 were analysed. 7,467 (80.8%) were non-squamous and 1,772 (19.2%) were squamous. Tumour marker testing was performed in 85.0% of patients with non-squamous tumours vs 56.3% in those with squamous tumours (p-value < 0.001). The global testing of EGFR, ALK, and ROS1 was 78.9, 64.7, 35.6% respectively, in non-squamous histology. PDL1 was determined globally in the same period (46.9%), although if we focus on the last 3 years it exceeds 85%. There has been a significant increase in the last few years of all determinations and there are even close to 10% of molecular determinations that do not yet have targeted drug approval but will have it in the near future. 4,115 cases had a positive result (44.5%) for either EGFR, ALK, KRAS, BRAF, ROS1, or high PDL1. CONCLUSIONS: Despite the lack of a national project and standard protocol in Spain that regulates the determination of biomarkers, the situation is similar to other European countries. Given the growing number of different determinations and their high positivity, national strategies are urgently needed to implement next-generation sequencing (NGS) in an integrated and cost-effective way in lung cancer.

Assessment of the need of a waiting period after pulmonary vein isolation with the ablation index software.

PURPOSE: Since the widespread availability of contact-force sensing catheters, the need for a waiting period after pulmonary vein isolation (PVI) has not been reassessed. We aim to evaluate whether a waiting period is still necessary after PVI guided by the ablation Index (AI). METHODS: Prospective, multicenter, randomized study of consecutive patients referred for paroxysmal atrial fibrillation (AF) ablation from May 2019 to February 2020. Patients were randomized in a 1:1 ratio to PVI with versus without a waiting period of 20 min. Acute pulmonary vein (PV) reconnection after adenosine challenge was the primary endpoint. A per-protocol analysis was designed to determine whether a strategy of dismissing the waiting period after PVI was noninferior to waiting for 20 min for identifying acute PV reconnection. PVI was guided by tailored AI values and an interlesion distance ≤6 mm. RESULTS: During the enrollment period, 167 patients (56% males, mean age of 57 ± 14 years) fulfilled the study inclusion criteria - 84 patients (308 PV) in the waiting period group (Group A) and 83 patients (314 PV) in the group without a waiting period (Group B). Acute PV reconnection was identified in 3.8% (95% confidence interval [CI], 1.7%-5.9%) of PVs in the study group B compared to 2.9% (95% CI, 1.0%-4.8%) of PVs in the Group A (p = .002 for non-inferiority). At 1-year follow-up, there was no significant difference in arrhythmia recurrence between groups (9.5% in Group A vs. 9.6% in Group B, hazard ratio: 1.03 [95% CI, 0.39-2.73], p = .98). CONCLUSION: In paroxysmal AF patients submitted to ablation, a tailored PVI guided by the AI rendered a 20-min waiting period unnecessary.

Chronodisruption and Ambulatory Circadian Monitoring in Cancer Patients: Beyond the Body Clock.

PURPOSE OF REVIEW: Circadian rhythms impose daily rhythms a remarkable variety of metabolic and physiological functions, such as cell proliferation, inflammation, and DNA damage response. Accumulating epidemiological and genetic evidence indicates that circadian rhythms' disruption may be linked to cancer. The integration of circadian biology into cancer research may offer new options for increasing cancer treatment effectiveness and would encompass the prevention, diagnosis, and treatment of this disease. RECENT FINDINGS: In recent years, there has been a significant development and use of multi-modal sensors to monitor physical activity, sleep, and circadian rhythms, allowing, for the very first time, scaling accurate sleep monitoring to epidemiological research linking sleep patterns to disease, and wellness applications providing new potential applications. This review highlights the role of circadian clock in tumorigenesis, cancer hallmarks and introduces the state-of-the-art in sleep-monitoring technologies, discussing the eventual application of insights in clinical settings and cancer research.