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The long-term implications of pacemaker insertion in younger adults are poorly described in the literature.We performed a retrospective analysis of consecutive younger adult patients (18-50 yrs) undergoing pacemaker implantation at a quaternary hospital between 1986-2020. Defibrillators and cardiac resynchronisation therapy devices were excluded. All clinical records, pacemaker checks and echocardiograms were reviewed.Eighty-one (81) patients (median age 41.0 yrs IQR=35-47.0, 53% male) underwent pacemaker implantation. Indications were complete heart block (41%), sinus node dysfunction (33%), high grade AV block (11%) and tachycardia-bradycardia syndrome (7%). During a median 7.9 (IQR=1.1-14.9) years follow-up, nine patients (11%) developed 13 late device-related complications (generator or lead malfunction requiring reoperation [n=11], device infection [n=1] and pocket revision [n=1]). Five (5) of these patients were40 years old at time of pacemaker insertion. At long-term follow-up, a further nine patients (11%) experienced pacemaker-related morbidity from inadequate lead performance managed with device reprogramming. Sustained ventricular tachycardia was detected in two patients (2%). Deterioration in ventricular function (LVEF decline10%) was observed in 14 patients (17%) and seven of these patients required subsequent biventricular upgrade. Furthermore, four patients (5%) developed new tricuspid regurgitation (moderate-severe). Of 69 patients with available long-term pacing data, minimal pacemaker utilisation (pacing5% at all checks) was observed in 13 (19%) patients.Pacemaker insertion in younger adults has significant long-term implications. Clinicians should carefully consider pacemaker insertion in this cohort given risk of device-related complications, potential for device under-utilisation and issues related to lead longevity. In addition, patients require close follow-up for development of structural abnormalities and arrhythmias.

Background: The diagnostic work-up for cardiac arrest from ventricular tachyarrhythmias occurring in younger adults and structurally normal hearts is variable and often incomplete. Methods: We reviewed records for all recipients of a secondary prevention implantable cardiac defibrillator (ICD) younger than 60 years at a single quaternary referral hospital from 2010-2021. Patients were included if they had unexplained ventricular arrhythmias (UVA) and absence of structural heart disease on echocardiogram, normal coronary assessment and no clear diagnostic features on ECG. We specifically evaluated the adoption rate of five modalities of ‘second-line’ cardiac investigations: cardiac magnetic resonance imaging (CMR), exercise ECG, flecainide challenge, electrophysiology study (EPS) and genetic testing. We also evaluated patterns of anti-arrhythmic drug therapy and device-detected arrhythmias and compared them with secondary prevention ICD recipients with a clear aetiology found on initial assessment. Results: 102 recipients of a secondary prevention ICD under the age of 60 were analysed. 39 patients (38.2%) were identified with UVA and were compared with the remaining 63 patients with VA of clear aetiology (61.8%). UVA patients were younger (35.6 ± 13.0 years vs 46.0 ± 8.6 years, pConclusion: In this real-world analysis of patients with UVA, the diagnostic work-up is often incomplete. While CMR was increasingly utilized at our institution, investigations for channelopathies and genetic causes appear to be underutilized. Implementation of a systematic protocol for work-up of these patients requires further study.

Background Exclusion of left atrial appendage thrombus (LAAT) by transoesophageal echocardiography (TOE) is recommended in patients with inadequate anticoagulation prior to direct cardioversion (DCR) or catheter ablation for atrial fibrillation/flutter (AF/AFL). LAAT risk factors in this population remain poorly defined. Purpose Determine LAAT predictors in AF/AFL patients undergoing pre-procedural TOE. Methods We evaluated available clinical and transthoracic echocardiographic (TTE) parameters in AF/AFL patients undergoing TOE between 1999–2022 in our institution in Melbourne, Australia. Regression analysis identified predictors of LAAT, which were applied to a weighted score developed in the derivation cohort (70%) and validated in the remaining 30%. Results Of 627 patients (age 62±12 years, 27% female, AF 84%,AFL 16%, left ventricular ejection fraction (LVEF) 44±20%), 24% had LAAT and 13.8% dense spontaneous echo contrast precluding DCR. Anticoagulation was NOAC 56.5%, warfarin 32.1% and none in 11.4%. In the LAAT cohort, thrombus resolution occurred in 39% on serial transoesophageal imaging with a median time to resolution of 131 days (IQR 54–398). Diabetes (p=0.004), prior stroke (p=0.009), coronary disease (p=0.015), renal impairment (p2 (73% vs. 55%, p Conclusion A novel LAAT risk model comprising clinical and echocardiographic parameters enhances risk prediction over CHADS2VASc in AF/AFL and may guide the need for pre-procedural TOE imaging. Funding Acknowledgement Type of funding sources: None.

3D bioprinting has recently emerged as a very useful tool in tissue engineering and regenerative medicine. However, developing suitable bioinks to fabricate specific tissue constructs remains a challenging task. Herein, we report on a nanocellulose/chitosan-based bioink, which is compatible with a 3D extrusion-based bioprinting technology, to design and engineer constructs for bone tissue engineering and regeneration applications. Bioinks were prepared using thermogelling chitosan, glycerophosphate, hydroxyethyl cellulose, and cellulose nanocrystals (CNCs). Formulations were optimized by varying the concentrations of glycerophosphate (80-300 mM), hydroxyethyl cellulose (0-0.5 mg/mL), and CNCs (0-2% w/v) to promote fast gelation kinetics (7 s) at 37 °C and retain the shape integrity of constructs post 3D bioprinting. We investigated the effect of CNCs and pre-osteoblast cells (MC3T3-E1) on the rheological properties of bioinks, bioink printability, and mechanical properties of bioprinted scaffolds. We demonstrate that the addition of CNCs and cells (5 million cells/mL) significantly improved the viscosity of bioinks and the mechanical properties of chitosan scaffolds post-fabrication. The bioinks were biocompatible and printable at an optimized range of printing pressures (12-20 kPa) that did not compromise cell viability. The presence of CNCs promoted greater osteogenesis of MC3T3-E1 cells in chitosan scaffolds as shown by the upregulation of alkaline phosphatase activity, higher calcium mineralization, and extracellular matrix formation. The versatility of this CNCs-incorporated chitosan hydrogel makes it attractive as a bioink for 3D bioprinting to engineer scaffolds for bone tissue engineering and other therapeutic applications.

Develop a prototype steroid eluting stent suitable for endoscopic treatment of subglottic stenosis. Rectangular-shaped spoke design stents thermally molded into horseshoe-shaped stents were developed using AutoCAD program, and printed on a Lulzbot 3D printer with polycaprolactone (PCL). Kenalog saturated AEROSIL 200 was embedded in the PCL filament. Horizontal radial force measurements were measured at baseline, 1 day, and 1 month when deformation switched from bending to compression. Amount of Kenalog eluted after 1 day, 1 week and 1 month were measured using HPLC. Horizontal pressure applied to the PCL stent corresponding to a 5–0 ET were 1.27 ± 0.38 lb. at baseline, 1.79 ± 0.045 lb. at 1 day, 1.94 ± − 0.22 lb. at 1 week and 2.07 ± 0.11 lb. at 1 month. The horizontal pressure applied to PCL stent corresponding to an 8–0 ET tube were 0.82 ± 0.018 lb. at baseline, 1.008 ± 0.045 lb. at 1 day, 0.95 ± − 0.064 lb. at 1 week and 1.078 ± 0.021 lb. at 1 month. The amount of Kenalog eluted increased from 5.78 µg/mL at 1 day to 15.01 µg/mL at 1 week to 19.35 µg/mL at 1 month. This proof-of-concept project is an initial step to demonstrate and create a novel stent in the treatment of subglottic stenosis that applies expansile force on the trachea, elutes steroids and dissolves. Over time the expansile force along the trachea increases allowing the PCL to mucosalize, while it dissolves and continues to elute steroids. The limitations of this in vitro study necessitate experiments on animal models, such as rabbit tracheas to observe for complications and histologic changes. This proof-of-concept project is a Level 5 mechanism-based reasoning study.

Majority of methods currently used for quality assessment of tissue engineered medical products (TEMPs) are offline and destructive in nature, which is one of the factors impeding the scale up and translation of these technologies. In this study, we investigate quality assessment of TEMP via dielectric impedance spectroscopy (DIS) and supervised machine learning (ML) as a non-destructive alternative that requires minimal human intervention. 3D printed, NaOH-treated polycaprolactone (PCL) scaffolds seeded with human adipose-derived stem cells (hASC), NIH 3T3, MG63, and human chondrocyte cells were assessed via DIS over 4 days of in vitro culture. The results showed that the cell type and duration in culture had a significant effect on the delta permittivity (Δe, an important DIS metric. Five supervised ML algorithms – K Nearest Neighbors (KNN), Logistic Regression, Random Forest Classifiers, Support Vector Machines, and artificial neural network – were then used to analyze the comprehensive structured permittivity datasets to determine their ability to discern between different cell types and culture durations. The KNN algorithm demonstrated the best accuracy (99%). The outcomes of this study demonstrate the approach of using DIS and supervised ML in conjunction for assessment of TEMPs in an automated manufacturing system.

Biocompatible polymer fibers have garnered significant interest due to their unique properties. Applications range from absorbent media to tissue engineering and drug delivery products. Many manufacturing processes produce such fibers, but a gap exists in highly scalable processes for fibers loaded with thermolabile additives like pharmaceuticals. This study investigates preliminary process-structure-function relationships of solution blown poly(ethylene oxide) fibers loaded with doxycycline, a drug that has demonstrated antibiotic, anti-inflammatory, and anti-tumoral properties. After parameter screening, a factorial experiment mapped the solution blowing design space with a multi-nozzle apparatus. A 1 mm-thick mat was fabricated comprising doxycycline loaded polymer fibers with a mean diameter of 552 ± 200 nm. Study of release kinetics showed the doxycycline released with a significant burst effect over approximately 1 minute. This study highlights solution blowing as a scalable manufacturing platform for fabricating poly(ethylene oxide) fibers loaded with this impactful drug.