Sex-specific outcomes and left atrial remodeling following catheter ablation of persistent atrial fibrillation: results from the DECAAF II trial.

BACKGROUND: Catheter ablation is recognized as an effective treatment for atrial fibrillation (AF). Despite its effectiveness, significant sex-specific differences have been observed, which influence the outcomes of the procedure. This study explores these differences in a cohort of patients with persistent AF. We aim to assess sex differences in baseline characteristics, symptoms, quality of life, imaging findings, and response to catheter ablation in patients with persistent AF. METHODS: This post hoc analysis of the DECAAF II trial evaluated 815 patients (161 females, 646 males). Between July 2016 and January 2020, participants were enrolled and randomly assigned to receive either personalized ablation targeting left atrial (LA) fibrosis using DE-MRI in conjunction with pulmonary vein isolation (PVI) or PVI alone. In this analysis, we aimed to compare female and male patients in the full cohort in terms of demographics, risk factors, medications, and outcomes such as AF recurrence, AF burden, LA volume reduction assessed by LGE-MRI before and 3 months after ablation, quality of life assessed by the SF-36 score, and safety outcomes. Statistical methods included t-tests, chi-square, and multivariable Cox regression. RESULTS: Females were generally older with more comorbidities and experienced higher rates of arrhythmia recurrence post-ablation (53.3% vs. 40.2%, p < 0.01). Females also showed a higher AF burden (21% vs. 16%, p < 0.01) and a smaller reduction in left atrial volume indexed to body surface area post-ablation compared to male patients (8.36 (9.94) vs 11.35 (13.12), p-value 0.019). Quality of life scores were significantly worse in females both pre- and post-ablation (54 vs. 66 pre-ablation; 69 vs. 81 post-ablation, both p < 0.01), despite similar improvements across sexes. Safety outcomes and procedural parameters were similar between male and female patients. CONCLUSION: The study highlights significant differences in the outcomes of catheter ablation of persistent AF between sexes, with female patients showing worse quality of life, higher recurrence of AF and AF burden after ablation, and worse LA remodeling.

Comprehensive atrial fibrillation burden and symptom reduction post-ablation: insights from DECAAF II.

AIMS: Traditional atrial fibrillation (AF) recurrence after catheter ablation is reported as a binary outcome. However, a paradigm shift towards a more granular definition, considering arrhythmic or symptomatic burden, is emerging. We hypothesize that ablation reduces AF burden independently of conventional recurrence status in patients with persistent AF, correlating with symptom burden reduction. METHODS AND RESULTS: Ninety-eight patients with persistent AF from the DECAAF II trial with pre-ablation follow-up were included. Patients recorded daily single-lead electrocardiogram (ECG) strips, defining AF burden as the proportion of AF days among total submitted ECG days. The primary outcome was atrial arrhythmia recurrence. The AF severity scale was administered pre-ablation and at 12 months post-ablation. At follow-up, 69 patients had atrial arrhythmia recurrence and 29 remained in sinus rhythm. These patients were categorized into a recurrence (n = 69) and a no-recurrence group (n = 29). Both groups had similar baseline characteristics, but recurrence patients were older (P = 0.005), had a higher prevalence of hyperlipidaemia (P = 0.007), and had a larger left atrial (LA) volume (P = 0.01). There was a reduction in AF burden in the recurrence group when compared with their pre-ablation burden (65 vs. 15%, P < 0.0001). Utah Stage 4 fibrosis and diabetes predicted less improvement in AF burden. The symptom severity score at 12 months post-ablation was significantly reduced compared with the pre-ablation score in the recurrence group, and there was a significant correlation between the reduction in symptom severity score and the reduction in AF burden (R = 0.39, P = 0.001). CONCLUSION: Catheter ablation reduces AF burden, irrespective of arrhythmia recurrence post-procedure. There is a strong correlation between AF burden reduction and symptom improvement post-ablation. Notably, elevated LA fibrosis impedes AF burden decrease following catheter ablation.

Effects of Prokineticins on Cerebral Cell Function and Blood-Brain Barrier Permeability.

Prokineticins are a family of small proteins with diverse roles in various tissues, including the brain. However, their specific effects on different cerebral cell types and blood-brain barrier (BBB) function remain unclear. The aim of this study was to investigate the effects of PROK1 and PROK2 on murine cerebral cell lines, bEnd.3, C8.D30, and N2a, corresponding to microvascular endothelial cells, astrocytes and neurons, respectively, and on an established BBB co-culture model. Western blot analysis showed that prokineticin receptors (PROKR1 and PROKR2) were differentially expressed in the considered cell lines. The effect of PROK1 and PROK2 on cell proliferation and migration were assessed using time-lapse microscopy. PROK1 decreased neural cells' proliferation, while it had no effect on the proliferation of endothelial cells and astrocytes. In contrast, PROK2 reduced the proliferation of all cell lines tested. Both PROK1 and PROK2 increased the migration of all cell lines. Blocking PROKRs with the PROKR1 antagonist (PC7) and the PROKR2 antagonist (PKR-A) inhibited astrocyte PROK2-mediated migration. Using the insert co-culture model of BBB, we demonstrated that PROKs increased BBB permeability, which could be prevented by PROKRs' antagonists.

Smartphone AF Burden During the Blanking Period Predicts Catheter Ablation Outcomes: Insights From DECAAF II.

BACKGROUND: Atrial fibrillation (AF) recurrence during the blanking period is under investigated. With the rise of smartphone-based electrocardiogram (ECG) monitoring, there's potential for better prediction and understanding of AF recurrence trends. OBJECTIVES: In this study the authors hypothesize that AF burden derived from a single-lead Smartphone ECG during the blanking period predicts recurrence of atrial arrhythmias after ablation. METHODS: 630 patients with persistent AF undergoing ablation were included from the DECAAF II (Effect of MRI-Guided Fibrosis Ablation vs Conventional Catheter Ablation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation) trial. Patients recorded daily ECG strips using a smartphone device. AF burden was defined as the ratio of ECG strips with AF to the total number of strips submitted. The primary outcome was the recurrence of atrial arrhythmia. RESULTS: Recurrence occurred in 301 patients during the 18-month follow-up period. In patients who developed recurrent arrhythmia after 90 days of follow-up, AF burden during the blanking period was significantly higher when compared with patients who remained in sinus rhythm (31.3% vs 7.5%; P < 0.001). AF burden during the blanking period was an independent predictor of arrhythmia recurrence (HR: 1.41; 95% CI: 1.36-1.47; P < 0.001). Through grid searching, an AF burden of 18% best discriminates between recurrence and no-recurrence groups, yielding a C-index of 0.748. After a follow-up period of 18 months, recurrence occurred in 33.7% of patients (147 of 436) with an AF burden <18% and in 79.4% of patients (154 of 194) with an AF burden >18% (HR: 4.57; 95% CI: 3.63-5.75; P < 0.001). CONCLUSIONS: A high AF burden derived from a smartphone ECG during the blanking period is a strong predictor of atrial arrhythmia recurrences after ablation.

Early Remodeling of the Left Atrium Following Catheter Ablation of Atrial Fibrillation: Insights From DECAAFII.

BACKGROUND: Left atrial (LA) enlargement is prevalent among atrial fibrillation (AF) patients and constitutes an important marker of atrial myopathy. Several studies have described reduction in LA volume post-catheter ablation (CA) of AF, however, none have investigated differences related to additional ablation outside the pulmonary veins (PVs). OBJECTIVES: The authors sought to study early LA remodeling following CA of persistent AF and the impact of additional, fibrosis-guided extra-PV ablation. METHODS: In this DECAAF II (Effect of MRI-Guided Fibrosis Ablation vs Conventional Catheter Ablation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation) trial subanalysis, patients with persistent AF were randomized to receive pulmonary vein isolation (PVI) only or PVI + fibrosis-guided ablation. Late gadolinium enhancement magnetic resonance imaging (LGE-MRI) was performed before and 3 months after CA. Patients were followed up with single-lead electrocardiogram devices for 12 to18 months. AF burden was calculated as days with AF divided by days monitored. RESULTS: This analysis included 733 patients. The mean LA volume index (LAVI) before ablation was 62.0 mm3/m2 and after ablation was 51.3 mm3/m2, with a mean reduction of 10.7 mm3/m2 (P < 0.001). Patients in the fibrosis-guided ablation arm had more volume reduction than did those in the PVI-only group (12.1 mm3/m2 vs 9.3 mm3/m2; P = 0.02). LAVI reduction was greater in patients with heart failure (15.7 vs 8.9; P = 0.001) and was associated with improved left ventricular ejection fraction (LVEF) (r = 0.23; P < 0.001), reduced AF burden (r = -0.173; P < 0.001), improved LVEF, and improved quality of life (r = 0.146; P < 0.001). CONCLUSIONS: We confirmed the presence of LA remodeling within 3 months after ablation for persistent AF. Importantly, we saw more LA volume reductions in patients in the PVI + fibrosis-guided ablation arm in comparison with PVI only, and in patients with LV dysfunction. LA volume reduction in response to CA is associated with decreased arrhythmia recurrence, reduced AF burden, and improved LVEF and quality of life.

Effect of fibrosis regionality on atrial fibrillation recurrence: insights from DECAAF II.

AIMS: The amount of fibrosis in the left atrium (LA) predicts atrial fibrillation (AF) recurrence after catheter ablation (CA). We aim to identify whether regional variations in LA fibrosis affect AF recurrence. METHODS AND RESULTS: This post hoc analysis of the DECAAF II trial includes 734 patients with persistent AF undergoing first-time CA who underwent late gadolinium enhancement magnetic resonance imaging (LGE-MRI) within 1 month prior to ablation and were randomized to MRI-guided fibrosis ablation in addition to standard pulmonary vein isolation (PVI) or standard PVI only. The LA wall was divided into seven regions: anterior, posterior, septal, lateral, right pulmonary vein (PV) antrum, left PV antrum, and left atrial appendage (LAA) ostium. Regional fibrosis percentage was defined as a region's fibrosis prior to ablation divided by total LA fibrosis. Regional surface area percentage was defined as an area's surface area divided by the total LA wall surface area before ablation. Patients were followed up for a year with single-lead electrocardiogram (ECG) devices. The left PV had the highest regional fibrosis percentage (29.30 ± 14.04%), followed by the lateral wall (23.23 ± 13.56%), and the posterior wall (19.80 ± 10.85%). The regional fibrosis percentage of the LAA was a significant predictor of AF recurrence post-ablation (odds ratio = 1.017, P = 0.021), and this finding was only preserved in patients receiving MRI-guided fibrosis ablation. Regional surface area percentages did not significantly affect the primary outcome. CONCLUSION: We have confirmed that atrial cardiomyopathy and remodelling are not a homogenous process, with variations in different regions of the LA. Atrial fibrosis does not uniformly affect the LA, and the left PV antral region has more fibrosis than the rest of the wall. Furthermore, we identified regional fibrosis of the LAA as a significant predictor of AF recurrence post-ablation in patients receiving MRI-guided fibrosis ablation in addition to standard PVI.

Identifying the prognostic significance of early arrhythmia recurrence during the blanking period and the optimal blanking period duration: insights from the DECAAF II study.

OBJECTIVE: Early atrial arrhythmia recurrence following atrial fibrillation (AF) ablation is common. Current guidelines promulgate a 3-month blanking period. We hypothesize that early atrial arrhythmia recurrence during the blanking period may predict longer-term ablation outcomes. METHODS AND RESULTS: A total of 688 patients with persistent AF undergoing catheter ablation were included in the DECAAF II trial database. The primary endpoint of the study was the first confirmed recurrence of atrial arrhythmia. Recurrence was also monitored during the 90-day blanking period. A total of 287 patients experienced recurrent atrial arrhythmia during the blanking period, while 401 remained in sinus rhythm. Rates of longer-term arrhythmia recurrence were substantially higher among those who developed recurrence during the blanking period compared to those who remained in sinus rhythm throughout the blanking period (68% vs. 32%, P < 0.001). The study cohort was divided into three groups according to the timing of arrhythmia recurrence during the blanking period. Of those who had recurrent arrhythmia during the first month of the blanking period (Group 1), 43.9% experienced longer-term recurrence, compared to 61.6% who recurred during the second month of the blanking period (Group 2), and 93.3% of those who had arrhythmia recurrence during the third month (Group 3, P < 0.001). The risk of recurrent arrhythmia was highest in Group 3 (HR = 10.15), followed by Group 2 (HR = 2.35) and Group 1 (HR = 1.5). Receiver operating characteristic analysis was performed to assess the relationship between the timing of arrhythmia recurrence and the primary outcome (AUC = 0.746, P < 0.001). The optimal blanking period duration was identified as 34 days. Atrial fibrillation burden determined by smartphone electrocardiogram technology over the 18 months follow-up period was significantly higher in Group 3 (29%) compared to Groups 1 (6%) and 2 (7%) and in patients who stayed in sinus rhythm during the blanking period (5%) (P < 0.0001). CONCLUSION: Early atrial arrhythmia recurrence during the blanking period, particularly during the third month, is significantly associated with later recurrence. Although a blanking period is warranted, it should be abbreviated.

Baseline natriuretic peptides as a predictor of atrial fibrillation recurrence after radiofrequency-based pulmonary vein isolation in a non-heart failure population: A subanalysis from DECAAF II.

BACKGROUND: Brain natriuretic peptide (BNP) is a marker of myocardial stretch and may have prognostic significance in patients with atrial fibrillation (AF) without heart failure (HF). We investigated the association between baseline BNP levels and arrhythmia recurrence following pulmonary vein isolation (PVI) among patients with persistent AF without HF. METHODS: We analyzed 125 patients with persistent AF without HF who had baseline BNP measured from the DECAAF II trial. The primary outcome was arrhythmia recurrence following ablation. The baseline characteristics across the two groups were compared using Chi-square test and Wilcoxon rank test accordingly. Cox regression analysis was used to analyze the association between baseline BNP levels and the primary outcome. RESULTS: Across the entire cohort, 64 (51%) patients experienced arrhythmia recurrence. When comparing patients who experienced arrythmia recurrence to patients who did not, patients with recurrent arrhythmia had higher levels of pre-ablation BNP, as evidenced by differences in means (330.05 pg/mL) compared to patients without recurrent arrhythmia (182.39 pg/mL) (p < .05). A cut-off BNP value of 300 pg/mL provided the largest area under curve (AUC) of receiver-operating characteristic (ROC) curve on univariate logistic regression. On unadjusted Cox analysis, for every 100 unit increase in BNP, the hazard ratio for the primary outcome increased 1.09 (1.026-1.158) times (p = .004). After adjusting for sex, hypertension, and stroke, the results remained significant (HR = 1.8516, CI 95% [1.0139 - 3.381], p = .045). CONCLUSION: In the non-heart failure population, BNP levels predict AF recurrence following PVI in persistent AF patients.

Catheter ablation improved ejection fraction in persistent AF patients: a DECAAF-II sub analysis.

AIMS: The aim of our study was to assess differences in post-ablation atrial fibrillation (AF) recurrence and burden and to quantify the change in LVEF across different congestive heart failure (CHF) subcategories of the DECAAF-II population. METHODS AND RESULTS: Differences in the primary outcome of AF recurrence between CHF and non-CHF groups was calculated. The same analysis was performed for the three subgroups of CHF and the non-CHF group. Differences in AF burden after the 3-month blanking period between CHF and non-CHF groups was calculated. Improvement in LVEF was calculated and compared across the three CHF groups. Improvement was also calculated across different fibrosis stages. There was no significant differences in AF recurrence and AF burden after catheter ablation between CHF and non-CHF patients and between different CHF subcategories. Patients with heart failure with reduced ejection fraction (HFrEF) experienced the greatest improvement in EF following catheter ablation (CA, 16.66% ± 11.98, P < 0.001) compared to heart failure with moderately reduced LVEF, and heart failure with preserved EF (10.74% ± 8.34 and 2.00 ± 8.34 respectively, P-value < 0.001). Moreover, improvement in LVEF was independent of the four stages of atrial fibrosis (7.71 vs. 9.53 vs. 5.72 vs. 15.88, from Stage I to Stage IV respectively, P = 0.115). CONCLUSION: Atrial fibrillation burden and recurrence after CA is similar between non-CHF and CHF patients, independent of the type of CHF. Of all CHF groups, those with HFrEF had the largest improvement in LVEF after CA. Moreover, the improvement in ventricular function seems to be independent of atrial fibrosis in patients with persistent AF.

Conduction system disease in cardiac amyloidosis.

Cardiac amyloidosis (CA) has diverse and deleterious effects on the conductive system. Atrial fibrillation is by far the most common electrophysiological manifestation of CA and is associated with more mortality, morbidity, and hospitalizations. While AF increases the risk of thrombosis regardless of the CHA2DS2-VASc score, the risk of thromboembolism seems to be high even in CA patients without AF. AV Nodal disease is prevalent and may precede the diagnosis of CA. The incidence of ventricular arrhythmias remains disputed, and the role of implantable cardioverter defibrillator devices in CA patients is controversial. Newer therapies targeted against specific types of CA have been developed, but their effects on conductive system disease are not well studied.

Compliance Challenges in a Longitudinal COVID-19 Cohort Using Wearables for Continuous Monitoring: Observational Study.

BACKGROUND: The WEAICOR (Wearables to Investigate the Long Term Cardiovascular and Behavioral Impacts of COVID-19) study was a prospective observational study that used continuous monitoring to detect and analyze biometrics. Compliance to wearables was a major challenge when conducting the study and was crucial for the results. OBJECTIVE: The aim of this study was to evaluate patients' compliance to wearable wristbands and determinants of compliance in a prospective COVID-19 cohort. METHODS: The Biostrap (Biostrap USA LLC) wearable device was used to monitor participants' biometric data. Compliance was calculated by dividing the total number of days in which transmissions were sent by the total number of days spent in the WEAICOR study. Univariate correlation analyses were performed, with compliance and days spent in the study as dependent variables and age, BMI, sex, symptom severity, and the number of complications or comorbidities as independent variables. Multivariate linear regression was then performed, with days spent in the study as a dependent variable, to assess the power of different parameters in determining the number of days patients spent in the study. RESULTS: A total of 122 patients were included in this study. Patients were on average aged 41.32 years, and 46 (38%) were female. Age was found to correlate with compliance (r=0.23; P=.01). In addition, age (r=0.30; P=.001), BMI (r=0.19; P=.03), and the severity of symptoms (r=0.19; P=.03) were found to correlate with days spent in the WEAICOR study. Per our multivariate analysis, in which days spent in the study was a dependent variable, only increased age was a significant determinant of compliance with wearables (adjusted R2=0.1; ß=1.6; P=.01). CONCLUSIONS: Compliance is a major obstacle in remote monitoring studies, and the reasons for a lack of compliance are multifactorial. Patient factors such as age, in addition to environmental factors, can affect compliance to wearables.

Atrial fibrillation ablation as first-line therapy for patients with heart failure with reduced ejection fraction (HFrEF): evaluating the impact on patient survival.

INTRODUCTION: Atrial fibrillation and congestive heart failure share several pathophysiological mechanisms. As a result of their association, patients have worse outcomes than if either condition were present alone. AREAS COVERED: While multiple trials report no significant difference between the use of pharmacological rhythm control and the use of rate control in terms of mortality and morbidity in patients with HFrEF, there is evidence to suggest that catheter ablation is beneficial in this patient population. The present review aims to provide a comprehensive overview of catheter ablation as a treatment modality for atrial fibrillation in patients with HFrEF as well as evaluate its outcome on survival. EXPERT OPINION: An appropriate patient selection strategy for patients with HFrEF could be the next step in determining which patients might benefit most from catheter ablation. Future atrial fibrillation management may incorporate digital health and pulsed-field ablation.

CAR-T Cell Therapy for Solid Tumors: Are we Still That Far? a Systematic Review of Literature.

This systematic review aims to assess all the prospective studies published to date on the efficacy of CAR-T cell therapy in solid tumors. Databases searched were PubMed and Google Scholar from inception through May 1st 2021. Search query was (Chimeric antigen receptor) or (CAR-T) or (T-CAR). Twenty-nine prospective studies (265 patients) were included. Most published clinical trials are phase I. Clinical benefit was 100% in epithelial ovarian cancer, 70-82% in gastrointestinal tumors, 79% in mesothelioma, 63% in small-cell lung cancer, 24-67% in sarcoma, 50-62% in prostate cancer, and 45-50% in central nervous system tumors. No serious CAR-T cell specific serious toxicities were noted.