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Background: Patients with respiratory manifestations of acute COVID-19 infection have enlarged luminal areas of central conducting airways demonstrated on computed tomography imaging and abnormal pulmonary function. In some cases, COVID-19 symptoms may persist for more than 4 weeks, referred to as long COVID, and the effect on airway luminal area remains unknown. Herein, we report airway luminal cross-sections areas among a long COVID group, compared to individuals with an acute COVID-19. We aim to investigate if large conducting airways sizes are different between acute COVID-19 and long COVID patients. Methods: A cohort of 181 people with long COVID were screened, of which 20 people (9 men, 11 women; 55.9 ± 14.1 years) were included in analyses. Twenty age, height, and sex matched patients with an acute (< 4 weeks of persistent symptoms from diagnosis) COVID-19 infection (55.7 ± 15.2 years) served as a comparison group. We used a three-dimensional reconstruction of computed tomography imaging to measure luminal areas of the trachea, right and left main bronchi, bronchus intermediate, right and left upper lobe, and left lower lobe bronchi at proximal, middle, and distal cross-sectional points in both groups. Airway luminal area was taken as the average of the three points. We compared average lumen area of long COVID patients with acute COVID-19 individuals, using an independent samples t-test. Results: We found no significant difference comparing measurements of the following airway luminal cross-sectional areas: trachea (277.7 ± 100.4 vs. 268.0 ± 70.5 mm2 p=0.73), right main bronchus (191.0 ± 66.1 vs. 190.1 ± 49.0 mm2, p=0.96), bronchus intermediate (112.3 ± 33.4 vs. 109.3 ± 27.9 mm2, p=0.76), right upper lobe bronchus (74.4 ± 21.0 vs. 73.7 ± 25.5 mm2, p=0.92), left main bronchus (129.1 ± 50.1 vs. 136.9 ± 38.0 mm2, p=0.58), left lower lobe bronchus (57.8 ± 18.2 vs. 59.0 ± 13.4 mm2, p=0.82), and left upper lobe bronchus (80.1 ± 19.5 vs. 77.9 ± 22.9 mm2, p=0.75) in the long COVID and acute COVID-19 groups respectively. Conclusion: In patients with long COVID, compared to those with an acute COVID-19 infection, we did not see differences in central airway luminal areas. Further analysis of a larger cohort is needed to determine whether enlarged airway luminal areas, associated with acute COVID-19, persist in long COVID. This research will expand knowledge on functional consequences for patients with long COVID. Funding: F32HL154320 to JWS; 5R35HL139854 to MJJ. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract: Background and Aims The BNT162b2 and mRNA-1273 COVID-19 vaccines are efficacious in patients with inflammatory bowel disease; but there is a lack of data examining if holding immunosuppressive therapy around vaccination improves immune response. We studied the effect of holding IBD medications around the time of vaccination on antibody response and breakthrough COVID-19 infection. Methods Partnership to Report Effectiveness of Vaccination in populations Excluded from iNitial Trials of COVID is a prospective cohort of individuals with IBD receiving COVID-19 vaccination. Quantitative measurement of anti-receptor binding domain IgG antibodies to SARS-CoV-2 was performed 8 weeks after completing a vaccination series. Results A total of 1854 patients were included; 59% were on anti-tumour necrosis factor [TNF] [10% of these on combination therapy], 11% on vedolizumab, and 14% on ustekinumab; 11% of participants held therapy before or after vaccine administration for at least 2 weeks. Antibody levels were similar in participants continuing versus holding anti-TNF monotherapy before or after the second vaccine [BNT162b2: 10 μg/mL vs 8.9 μg/mL; mRNA-1273: 17.5 μg/mL vs 14.5 μg/mL]. Comparable results were seen in those on combination therapy. Antibody titres in those on ustekinumab or vedolizumab were higher compared with anti-TNF users, but there was no significant difference if the drug was held or continued [BNT162b2: 22.5 μg/mL vs 23 μg/mL; mRNA-1273: 88 μg/mL vs 51 μg/mL]. Holding therapy was not associated with decreased rate of COVID-19 infection compared with those not holding therapy [BNT162b2: 28% vs 29%; mRNA-1273: 19% vs 31%]. Conclusion We recommend continuing IBD medications while receiving mRNA COVID-19 vaccination without interruption.

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Idiopathic ventricular fibrillation (IVF) is responsible for 5-7% of sudden cardiac arrests in the absence of substrate for ventricular arrhythmia, structural diseases, or primary arrhythmic syndromes. The characteristics, management, and prognosis of these patients are unclear. Purpose To investigate the clinical features, management, and prognosis of IVF in our hospital healthcare system Methods Mayo Database Explorer software was used to identify IVF patients from our hospital electronic medical records between 1990 to 2022 in 5 states. The medical records were manually reviewed. Results A total of 132 patients were initially diagnosed with IVF. During the 9.2±6.8 years mean follow-up, 36 [27.3%] patients were later diagnosed with structural diseases or primary arrhythmic syndromes (dilated cardiomyopathy [41.7%], Long QT syndrome [27.8%], catecholaminergic polymorphic ventricular tachycardia [8.3%], Brugada syndrome [5.6%], mitral valve-related arrhythmia [5.6%], and short QT syndrome [2.8%]). Among the rest of the 96 patients with true IVF (mean age 38.4±15.7 years, male 59.4%, Caucasian 80.2%, hypertension 28.1%, diabetes 8.3%), 91 (94.8%) patients presented with out-of-hospital cardiac arrest and 88 (91.7%) patients had a history of syncope. Early repolarization and fragmented QRS were noted in 32 (33.3%) and 28 (29.1%) patients, respectively. Defibrillators were implanted in 92 (95.8%) patients. Genetic testing was performed in 35 (36.5%) patients, and possible associated mutations were found in 13 (37.1%) patients. An Electrophysiology study was conducted in 55 (57.3%) patients, and ventricular fibrillation was induced in 17 (30.9%) patients. The medical management with antiarrhythmic drugs was selected in 60 (62.5%) patients, and the catheter ablation ± anti-arrhythmic drugs was selected in 36 (37.5%) patients. The recurrence of ventricular fibrillation during 9.2±6.8 years of mean follow-up was significantly higher in the ablation strategy group (p=0.0003) (Figure 1). Conclusions We reported the largest cohort of IVF patients from a single healthcare system. Early repolarization and fragmented QRS were common in IVF. The possible associated mutations were found in one-third of IVF who underwent genetic testing. The ventricular fibrillation recurrences were significantly higher in the catheter ablation strategy group.

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Pfizer Background Type 1 long QT syndrome (LQT1) is a genetic channelopathy characterized by both haploinsufficient and dominant-negative loss-of-function pathogenic variants in the KCNQ1-encoded Kv7.1 K+ channels conducting IKs. Patients with LQT1 may manifest QT prolongation and ventricular arrhythmias that can culminate in sudden cardiac death. Purpose With this project, we aim to investigate whether our mutation independent, KCNQ1-specific suppression-replacement (SupRep) gene therapy can restore the deficient K+-channel and thereby restore the healthy phenotype. Methods Our proprietary dual component SupRep gene therapy was created by combining a custom-designed KCNQ1 shRNA and a shRNA-immune (shIMM) KCNQ1 cDNA into AAV9. In vivo AAV9-mediated KCNQ1SupRep gene therapy was performed by targeted intra-aortic root construct injection (1E12 vg/kg body weight) during balloon occlusion using a Swan Ganz catheter. 2 weeks after in vivo gene therapy, 12-lead ECGs were assessed in adult transgenic LQT1 (KCNQ1-Y315S, loss-of IKs) and wild-type (WT) rabbits to determine the effect of SupRep therapy on the rabbit’s QTc. Patch-clamp and calcium transient measurements were performed in isolated ventricular cardiomyocytes to evaluate the effect of SupRep on the cardiomyocyte’s action potential duration (APD90) and Ca2+ transient duration (Ca2+90) both, in vitro – after plasmid transfection, and in vivo – after AAV9-mediated gene therapy. AAV9-KCNQ1-construct expression was verified with immunohistochemistry targeting the GFP-tag. Results After injection of 3 LQT1 rabbits so far, no significant changes were observed in the LQT1 rabbits’ QTc before and after in vivo AAV9-mediated gene therapy. However, at the cellular level, LQT1 cardiomyocytes transfected in vitro with the SupRep-plasmid demonstrated a significant reduction of APD90 (ms, 1Hz stimulation at 37°) compared to LQT1 control cells (SupRep-in-vitro, 358±21 vs. control 447±22, p&lt;0.05). No differences were observed between sham-plasmid transfected cardiomyocytes and LQT1 control cells after one day of culturing. Similarly, cardiomyocytes isolated from the 3 LQT1 rabbits that underwent in vivo SupRep gene therapy demonstrated pronounced shortening of both APD90 and Ca2+90 compared to LQT1 controls, leading to levels similar to WT controls (APD90, 1Hz, 37°: LQT1: 530±18, WT: 445±18, LQT1-SupRep: 375±25, p&lt;0.0001 LQT1 vs. LQT1-SupRep, p=ns LQT1-SupRep vs. WT) (Ca2+90: LQT1: 487±23, WT: 346±16, LQT1-SupRep: 393±19, p&lt;0.0001 LQT1 vs. LQT1-SupRep, p=ns LQT1-SupRep vs. WT). Conclusion In vivo KCNQ1-suppression-replacement gene therapy normalizes cellular action potential and calcium transient duration in transgenic LQT1 rabbits. Further in vivo experiments will be conducted to evaluate whether this therapeutic correction at the cardiomyocyte level will translate into normalization of the LQT1 rabbits’ QTc both at rest and during stress testing.

Abstract Introduction Inflatable penile prostheses have favorable short-term results for men with refractory erectile dysfunction, but few studies have evaluated the long-term outcomes, including in a VA population. Objective This study aims to evaluate the outcomes and satisfaction rates using the novel validated survey, the Satisfaction Survey for Inflatable Penile Implant (SSIPI) of a long-term single-center VA practice. Methods Chart reviews were completed as a Quality Improvement project. All patients who underwent a primary inflatable penile prosthesis implantation from 1993-2021 were included. Demographics and data were collected; SSIPI was administered to men who could be reached. Statistical analyses were performed. Results 114 men were identified, 82 alive and 32 deceased. In the cohort we contacted, mean age at time of surgery was 62.6 years old and mean follow-up 78.2 months (5-234 months). Average SSIPI scores were 64.5/80 (26-80). Smokers were less satisfied with length of penis vs. non-smokers (SSIPI#8 = 2.89 vs 3.93, p=0.032). Men with diabetes were more likely to express regret about undergoing IPP surgery compared to men without (SSIPI#4 = 4.05 vs 4.38, p=0.0029). Men with an ASA score of 2 or less had higher total SSIPI scores compared to ASA score of 3+ (70.36 vs. 61.13, p=0.046). Conclusions Long-term satisfaction with IPP in a veteran population appears favorable. However, a significant number of these men still score poorly on SSIPI and/or have complications. The utility of this novel assessment instrument appears excellent. Men with smoking, diabetes, and higher overall comorbidities may find fewer positive results. Disclosure No

Abstract Introduction Climacturia has been reported in up to 64% of patients following radical prostatectomy (RP). In 2017, a prospective multicenter, multinational, investigational pilot study was conducted examining outcomes using a novel surgical technique, the Mini-Jupette sling, for the management of men with post-RP erectile dysfunction (ED) and climacturia and/or minimal stress urinary incontinence (SUI). We sought to report the 5-year outcomes from this original cohort. Objective To assess long-term safety and efficacy of the mini-jupette sling in the treatment of ED and concomitant mild SUI and/or climacturia Methods We identified patients who were enrolled in the previous multicenter study with post-RP ED and climacturia and/or mild SUI (2 ppd) and underwent IPP insertion with simultaneous placement of a Mini-Jupette sling. Data including current ppd, improvement in climacturia, complications, need for revision of IPP or additional urinary incontinence surgery, and date of most recent follow-up were collected. Results Of the original 38 patients, 5 have since died and 10 were lost to follow-up with 23/38 (61%) patients available for evaluation of long-term outcomes. The average follow-up time was 59 months (SD= 8.8) with a mean age of 69 years (SD= 6.8). Most patients (n=21, 91%) had subjective improvement of SUI and climacturia. One patient with persistent bothersome incontinence underwent artificial urinary sphincter (AUS) placement in 2018 with no complications, while the other is still considering a repeat procedure due to minor but persistent SUI. The mean ppd decreased from 1.4 preoperatively to 0.3 at a mean 5 years of follow-up. Most patients reported satisfaction in their urinary symptoms with 91% and 73% reporting improvement in SUI and climacturia respectively, compared to 86% and 93% respectively in the original series. One (4.3%) patient had an IPP revision for pump malfunction. There were no device infections reported. Conclusions The Mini-Jupette sling appears to be a safe and effective procedure with durable improvements in SUI and climacturia at 5 years of follow-up. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast, Clarus Therapeutics, Antares Pharma, Acerus, Intuitive Surgical, Fidalis, Hims & Hers Health Inc

Abstract Remote monitoring is beneficial for the management of patients with cardiovascular implantable electronic devices by impacting morbidity and mortality. With increasing numbers of patients using remote monitoring, keeping up with higher volume of remote monitoring transmissions creates challenges for device clinic staff. This international multidisciplinary document is intended to guide cardiac electrophysiologists, allied professionals, and hospital administrators in managing remote monitoring clinics. This includes guidance for remote monitoring clinic staffing, appropriate clinic workflows, patient education, and alert management. This expert consensus statement also addresses other topics such as communication of transmission results, use of third-party resources, manufacturer responsibilities, and programming concerns. The goal is to provide evidence-based recommendations impacting all aspects of remote monitoring services. Gaps in current knowledge and guidance for future research directions are also identified.

AbstractRemote monitoring is beneficial for the management of patients with cardiovascular implantable electronic devices by impacting morbidity and mortality. With increasing numbers of patients using remote monitoring, keeping up with higher volume of remote monitoring transmissions creates challenges for device clinic staff. This international multidisciplinary document is intended to guide cardiac electrophysiologists, allied professionals, and hospital administrators in managing remote monitoring clinics. This includes guidance for remote monitoring clinic staffing, appropriate clinic workflows, patient education, and alert management. This expert consensus statement also addresses other topics such as communication of transmission results, use of third‐party resources, manufacturer responsibilities, and programming concerns. The goal is to provide evidence‐based recommendations impacting all aspects of remote monitoring services. Gaps in current knowledge and guidance for future research directions are also identified.