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Bispecific antibodies revolutionized immunotherapy by improving the specificity of target recognition and extending the spectrum of treatments by enabling efficient target and effector cell interaction. Engineering strategies have led to novel designs of tri- and multispecific antibodies, which combine even more beneficial properties and promise superior efficacy and safety. Several of them efficiently harvest the patient's immune response by addressing effector cells of the innate immune system. [ABSTRACT FROM AUTHOR]

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Background: Atrioesophageal fistula (AEF) is a worrisome complication of atrial fibrillation (AF) ablation. Its clinical manifestations and time course are unpredictable and may contribute to diagnostic and treatment delays. We conducted a systematic review of all available cases of AEF, aiming at characterizing clinical presentation, time course, diagnostic pitfalls, and outcomes. Methods: The digital search retrieved 150 studies containing 257 cases, 238 (92.6%) of which with a confirmed diagnosis of AEF and 19 (7.4%) of pericardioesophageal fistula. Results: The median time from ablation to symptom onset was 21 days (interquartile range [IQR]: 11–28). Neurological abnormalities were documented in 75% of patients. Compared to patients seen by a specialist, those evaluated at a walk‐in clinic or community hospital had a significantly greater delay between symptom onset and hospital admission (median: 2.5 day [IQR: 1–8] vs. 1 day [IQR: 1–5); p =.03). Overall, 198 patients underwent a chest scan (computed tomography [CT]: 192 patients and magnetic resonance imaging [MRI]: 6 patients), 48 (24.2%; 46 CT and 2 MRI) of whom had normal/unremarkable findings. Time from hospital admission to diagnostic confirmation was significantly longer in patients with a first normal/unremarkable chest scan (p <.001). Overall mortality rate was 59.3% and 26.0% survivors had residual neurological deficits at the time of discharge. Conclusions: Since healthcare professionals of any specialty might be involved in treating AEF patients, awareness of the clinical manifestations, diagnostic pitfalls, and time course, as well as an early contact with the treating electrophysiologist for a coordinated interdisciplinary medical effort, are pivotal to prevent diagnostic delays and reduce mortality. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the arrhythmia profile and ablation outcome in women with atrial fibrillation (AF) aged ≥75 years. Methods: A total of 573 consecutive female patients undergoing first AF ablation were classified into group 1: ≥75 years (n = 221) and group 2: < 75 years (n = 352). Isolation of PVs, posterior wall and superior vena cava was performed in all. Non‐PV triggers from other areas were ablated based on operator's discretion. Results: Group 1 had higher prevalence of hypertension (154 (69.7%) vs. 188 (53.4%), p <.001) and non‐paroxysmal AF (136 (61.5%) vs. 126 (35.8%), p <.001). Non‐PV triggers were detected in 194 (87.8%) patients from group 1 and 143 (40.6%) from group 2 (p <.001) and were ablated in 152 (68.8%) and 114 (32.4%) from group 1 and 2 respectively. Remaining patients (group 1: 69/221 and group 2: 238/352) received no additional ablation. At 4 years, 109 (49.3%) and 185 (52.6%) from group 1 and 2, respectively, were arrhythmia‐free, p =.69. When stratified by ablation‐strategy, success‐rate was similar across groups in patients receiving non‐PV trigger ablation (96 (63.2%) in group 1 and 76 (66.7%) in group 2, p =.61), whereas it was significantly lower in group 1 patients not receiving additional ablation compared to those from group 2 (13 (18.8%) vs. 109 (45.8%), p <.001). Conclusion: Non‐paroxysmal AF was more common in women aged ≥75 years. Furthermore, significantly higher number of non‐PV triggers were detected in elderly women and ablation of those provided similar ablation success as that in women aged < 75 years. [ABSTRACT FROM AUTHOR]

Introduction: Early evidence suggests that multipoint left ventricular pacing (MPP) may improve response to cardiac resynchronization therapy (CRT). It is unknown whether this benefit is sustained and cost‐effective. We used real‐world data to evaluate long‐term impact of MPP‐ON clinical status, heart failure hospitalizations (HFH) and costs. Methods: The Italian registry on multipoint left ventricular pacing is a prospective, multicenter registry of patients implanted with MPP‐enabled CRT devices. For this analysis, clinical and echocardiographic data were collected through 24 months and compared between patients with (MPP‐ON) or without (MPP‐OFF) early MPP activation at implant. The total cost of each HFH was estimated with national Italian reimbursement rates. Results: The study included 190 MPP‐OFF and 128 MPP‐ON patients with similar baseline characteristics. At 1 and 2 years, the MPP‐ON group had lower rates of HFH vs MPP‐OFF (1‐year hazard ratio [HR]: 0.14, P =.0014; 2‐year HR: 0.38, P =.009). The finding persisted in a subgroup of patients with consistent MPP activation through follow‐up (1‐year HR: 0.19; P =.0061; 2‐year HR: 0.39, P =.022). Total HFH per‐patient costs were lower in the MPP‐ON vs the MPP‐OFF group at 1 year (€101 ± 50 vs €698 ± 195, P <.001) and 2 years (€366 ± 149 vs €801 ± 203, P =.038). More MPP‐ON patients had ≥5% improvement in ejection fraction (76.8% vs 65.4%, P =.025) and clinical composite score (66.7% vs 47.5%, P =.01). Conclusions: In this multicenter clinical study, early MPP activation was associated with a significant reduction in cumulative HFH and related costs after 1 and 2 years of follow‐up. [ABSTRACT FROM AUTHOR]

Background: Multipoint pacing (MPP) may improve clinical outcomes in patients with cardiac resynchronization therapy defibrillators (CRT‐D), but its impact on battery longevity in a real‐world population has not been investigated in large trials. Objective: Compare projected battery longevity in CRT‐D patients with and without MPP during long‐term follow‐up. Methods: The Italian registry on multipoint left ventricular pacing (IRON‐MPP) is a prospective, multicenter registry of patients implanted with MPP‐capable CRT‐D devices. Projected battery longevity during follow‐up was compared for patients with MPP (MPP ON) vs single‐site (MPP OFF) left ventricular pacing at CRT‐D implantation. A sub‐analysis excluded crossover patients with MPP activation or deactivation occurring after implantation. A second sub‐analysis excluded patients with a right or left ventricular pacing amplitude >2.5 V. Results: Out of 237 CRT‐D patients (71 ± 9 years, 81% male) followed for 1.9 ± 0.8 years, 102 (43%) had MPP ON at implantation. Programmed atrial and ventricular outputs and percentage of pacing were similar between groups. MPP was associated with a 0.44 years reduction in projected battery longevity (P = .03) during long‐term follow‐up. Results were similar for the first and second sub‐analyses, with a 0.57 years (P < .001) and 0.71 years (P < .001) reduction in projected longevity, respectively. Conclusion: In this long‐term real‐world registry, early MPP activation is associated with less than a 1‐year reduction in projected battery life compared to single‐site biventricular pacing. [ABSTRACT FROM AUTHOR]

Abstract: Aims: This study investigated the impact of weight loss in longstanding persistent (LSPAF) patients undergoing catheter ablation (CA). Methods: Ninety consecutive obese LSPAF patients were approached; 58 volunteered to try weight loss interventions for up to 1 year (group 1), while 32 patients declined weight loss interventions and were included as a control (group 2). Both groups remained on antiarrhythmic drugs. If they continued to experience AF, CA was performed. Body weight was measured at 6‐month intervals and arrhythmia status was assessed by event recorder, electrocardiogram (ECG), and Holter monitoring. Symptom severity and quality of life (QoL) were evaluated by AFSS and SF‐36 survey, respectively. A scoring algorithm with two summary measures, physical component score (PCS) and mental component score (MCS), was prepared for QoL analysis. Results: Significant reduction in body weight (median −24.9 (IQR −19.1 to −56.7) kg, P < 0.001) was observed in the group 1 patients, while no such change was seen in group 2. The PCS and MCS scores improved significantly in group 1 only, with a change from baseline of 8.4 ± 3 (P = 0.013) and 12.8 ± 8.2 (P < 0.02). However, AF symptom severity remained unchanged from baseline in both groups (P = 0.84). All 90 patients eventually underwent CA and received PVAI+ posterior wall+ non‐PV triggers ablation. At 1‐year follow‐up after single procedure, 37 (63.8%) in group 1 and 19 (59.3%) patients in group 2 remained arrhythmia‐free off AAD (P = 0.68). Conclusion: In this prospective analysis, in LSPAF patients weight loss improved QoL but had no impact on symptom severity and long‐term ablation outcome. [ABSTRACT FROM AUTHOR]

Gender-Specific Link of Exercise Intensity With AF Background Despite widespread interest and extensive research, the association between different levels of physical activity (PA) and risk of atrial fibrillation (AF) is still not clearly defined. Therefore, we systematically evaluated and summarized the evidences regarding association of different intensity of PA with the risk of AF in this meta-analysis. Methods and Results An extensive literature search was performed on databases for studies showing association of exercise with AF risk. Twenty-two studies were identified that included 656,750 subjects. Meta-analytic estimates were derived using random-effects models and pooled odds ratio estimates were obtained. Potential sources of heterogeneity were examined in sensitivity analyses, and publication biases were estimated. Pooled analysis of 7 studies with 93,995 participants reported high risk of incident AF with sedentary lifestyle (pooled OR 2.47 [95% CI 1.25-3.7], P = 0.005). In 3 trials, 149,048 women involved in moderate PA were 8.6% less likely to develop AF compared to women with sedentary life (OR 0.91 [95% CI 0.78-0.97], P = 0.002). Women performing intense exercise were found to have 28% lower risk of AF (OR 0.72 [95% CI 0.57-0.88], P < 0.001). The overall pooled estimate indicated a protective impact of moderate PA in men (pooled OR 0.8133 [95% CI 0.26-1.004], P = 0.06) whereas vigorous PA was associated with a significantly increased AF risk (pooled OR 3.30 [1.97-4.63], P = 0.0002). Conclusion Sedentary lifestyle significantly increases and moderate amount of physical activity reduces the risk of AF in both men and women. However, intense exercise has a gender-specific association with AF risk. [ABSTRACT FROM AUTHOR]