Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a cystic tumor with a disease spectrum ranging from low-grade dysplasia to invasive carcinoma. The evidence for adjuvant treatment in invasive IPMN is limited and mostly derived from studies in conventional pancreatic ductal adenocarcinoma (PDAC). We performed a systematic review focusing on all clinical studies concerning the efficacy of adjuvant therapy in patients with invasive IPMN. We identified 8 retrospective cohort studies, using either adjuvant chemotherapy alone (n=1), adjuvant radiotherapy alone (n=1) or adjuvant chemotherapy in combination with radiation (n=6). Adjuvant therapy was associated with a survival benefit in 7 out of the 8 studies. Specific survival benefit was noted for patients with node-positive disease, higher TNM stage, positive resection margins, poor differentiation and tubular subtype. We conclude that adjuvant therapy may be beneficial in invasive IPMN, but current data suggest that it should be given selectively based on individual tumor characteristics. Further prospective, randomized studies are warranted.

Introduction: Cardiac resynchronization therapy (CRT) is an established treatment for heart failure in selected patients. However, current guideline indications do not accurately predict individual prognosis with CRT, and up to 30% are non-responders. Previous studies have shown that QRS area reduction following CRT is associated with improved survival. This study evaluates the incremental value of using QRS area derived from digital ECG recordings, preoperatively and during CRT pacing. Methods: Medical records of 445 patients receiving CRT implants at a large-volume tertiary care center in Sweden were retrospectively evaluated. Digital electrocardiograms (ECG) before and after CRT implantation were collected and ECG parameters were analyzed in relation to a primary composite endpoint of heart failure hospitalization or death from any cause. Results: 147 patients (33%) reached the primary endpoint (93 deaths and 103 heart failure hospitalizations) over a median follow-up time of 2.7 years. A larger pre-implant QRS area (HR, 0.89; [0.85-0.93]; p=<0.0001; adjusted HR, 0.93; [0.88-0.98]; p=0.011) and larger QRS area reduction (HR, 0.92; [0.88-0.96]; p=<0.0001; adjusted HR, 0.95; [0.90-0.99]; p=0.042) post-implant correlated with a reduced risk of reaching the primary endpoint. This association was seen in patients with native left bundle branch block morphology, non-specific intraventricular conduction delay, or paced ECG morphology but not in patients with right bundle branch block. Conclusion: Larger pre-implant QRS area and QRS area reduction was associated with better clinical outcome following CRT in this retrospective material. This knowledge could help optimize patient selection and postoperative management.

Funding Acknowledgements Type of funding sources: None. Introduction Cardiac resynchronization therapy (CRT) is an established treatment for heart failure in selected patients(1). A recently developed device-based algorithm for optimization of AV- and VV-timing (SyncAV) has shown promising acute hemodynamic improvement by tailoring the device settings for maximum reduction in QRS-duration(2). We aimed to evaluate if optimization by maximizing QRS reduction is feasible in an all-comer CRT population and if reduced QRS-duration is associated with a better clinical outcome. Methods Medical records of 254 consecutive patients with left bundle branch block receiving CRT implants during the period 2015-2020 were retrospectively evaluated. Implants from 2015-2017 were designated as control group. Typical programming in the control group included a short AV-time to ensure biventricular capture and synchronous pacing of the right and left ventricle, or in selected patients a slight preexitation (20-40 ms) of the left ventricle. Starting from 2018 and onwards, an active 12-lead electrogram (ECG) based optimization of QRS duration had been implemented and these patients were designated as the intervention group. QRS duration and morphology were evaluated in a structured way at various device settings, including use of specific device algorithms when applicable and manual modifications of AV- and VV-delays and LV only pacing when applicable, aiming to maximize reduction of QRS duration. Digital ECGs before and after CRT implantation were collected and QRS duration reduction was automatically analyzed. The primary endpoint was a composite of heart failure hospitalization or death from any cause. Results Patients were followed for up to 6 years (median 2.9 [1.8-4.1]), during which 82 patients (32%) reached the primary endpoint; 53 deaths (21%) and 58 (23%) heart failure hospitalizations. Median QRS duration pre-implant was 162ms [150-174] and post-implant 146ms [132-160]. Mean reduction in QRS duration was progressively larger for each year during the intervention period, changing from -9.5ms in the control group to -24 in the year 2020 (p=0.005). In Kaplan Meier analysis across all groups, QRS reduction &gt;14ms (median value) was associated with lower risk of death or heart failure hospitalization (p=0.049). In a multivariate model the hazard ratio was 0.60 [0.38-0.96] (p=0.03). Conclusion Implementing a general strategy of CRT device-optimization by aiming for shorter QRS duration is feasible in a structured clinical setting, and results in larger reductions in QRS duration post-implant. In patients with larger QRS reduction, compared to those with smaller QRS reduction, there is an association with a better clinical outcome, including lower risk of mortality and heart failure hospitalization. If confirmed in prospective trials, this strategy may become useful for improving clinical outcome for CRT recipients, regardless of device-brand and underlying etiology.