467 Update on supra-annular sizing of transcatheter aortic valve prostheses in raphe-type bicuspid aortic valve disease according to the LIRA method

Aims Transcatheter Aortic Valve Replacement (TAVR) in patients with bicuspid aortic valve (BAV) still represents a challenge due to the peculiar anatomy and the lack of consensus for the optimal CT scan sizing method for prosthesis selection. Recent evidences have shown that transcatheter heart valve (THV) anchoring in BAV patients might occur at the raphe-level, known as the LIRA (Level of Implantation at the RAphe) plane. Furthermore, a novel supra-annular sizing method based on the measurement of the perimeter at the raphe-level (LIRA-method) was shown to be safe and effective in 20 consecutive BAV patients with severe aortic stenosis. The purpose of this study was to confirm the safety and the efficacy of the LIRA method in a larger study population. Methods and results the LIRA plane method was applied to all consecutive patients with raphe-type BAV disease between November 2018 to September 2021 in our centre. We prospectively sized TAVI prosthesis according to the manufacture recommendations on the basis of baseline CT scan perimeters at the LIRA plane. Post-procedural device success, defined according to Valve Academic Research Consortium-2 (VARC-2) criteria, was evaluated in the overall cohort. Forty-four patients were identified as having a raphe-type BAV disease at pre-TAVI CT scans. Mean patient age was 80 ± 6.2 years and 74% were males; median Society of Thoracic Surgeons (STS) predicted risk of mortality score was 4.3 (3.0–6.5). Three different BAV anatomies (36 patients with BAV type 1 with calcific raphe, 5 patients with BAV type 1 with fibrotic raphe, and 3 patients with BAV type 2) were implanted with different types of TAVI prostheses (6 Acurate Neo 2,16 Acurate Neo, 21 Core Valve Evolut R/Pro , 1 Lotus) sized prospectively according to the LIRA plane method. In all patients, there was a significant discrepancy between LIRA and virtual basal ring (VBR) measurements with LIRA plane perimeter smaller than VBR perimeter (mean perimeter LIRA 73.1 ± 8.3 mm vs. mean perimeter VBR 81.5 ± 6.6 mm; P < 0.001). The prostheses were sized according to the manufacture recommendations on the basis of the LIRA plane perimeter (diameter prosthesis implanted/diameter prosthesis according to LIRA plane = 1) (DPI/DP LIRA = 1) and significantly downsized according to the VBR perimeter (DPI/DP VBR 0.89; P < 0.001). The median prosthesis size was 25 mm (23–27). Pre-dilatation was frequently performed (86%) with a median balloon size of 20 mm (18–22), whereas post-dilatation was applied in 27% of the cases with a median balloon size of 23 mm (20–26). The LIRA plane method appeared to be highly successful (100% VARC-2 device success) with no procedural mortality, no valve migration, residual trivial/mild paravalvular leak with no cases of moderate-severe regurgitation and low transprosthetic gradient (residual mean gradient of 8.3 ± 3.5 mmHg) with no cases of mean gradient >20 mmHg pre-discharge. The rate of new pacemaker implantation was 9%. Conclusions Supra-annular sizing according to the LIRA plane method confirmed to be safe with a high device success in a larger study population. The application of the LIRA plane method might optimize TAVI prosthesis sizing in patients with raphe-type BAV disease.

A nomogram to predict stricture-free survival in patients with ureteral stricture after balloon dilation

Background Balloon dilation is a commonly used minimally invasive endourological treatment of ureteral stricture, but the postoperative recurrence rate is relatively high. And factors contributing to recurrence after treatment are poorly understood. Herein, we sought to develop a novel clinical nomogram to predict ureteral stricture-free survival in patients suffering from ureter stricture and performed balloon dilation. Methods The nomogram was established based on a retrospective analysis of 321 patients who received endoscopic balloon dilation alone for ureter strictures from January 2016 to January 2020 in Sun Yat-sen Memorial Hospital using the Cox regression model. Perioperative clinical data and disease outcomes were analyzed. The primary endpoint was the onset of ureteral re-stricture after ureter balloon dilation. Discrimination of the nomogram was assessed by the concordance index (C-index) and the calibration curve. The results were internally validated using bootstrap resampling. Results Overall, 321 patients with a median follow-up of 590 days were enrolled in the study, among which 97 patients (30.2%) developed recurrence of ureteral stricture during follow-up. Five variables remained significant predictors of ureteral re-stricture after multivariable analyses: stricture nature (P < 0.001), urinary nitrite (P = 0.041), CKD (P = 0.005), stent retention time (P < 0.001), and balloon size (P = 0.029). The calibration craves for the probability of 1-, 3-, and 5-years stricture-free survival (SFS) presented satisfied with the consistency of nomogram prediction and actual observation. The C-index of the model was 0.74 (95% CI 0.70–0.79). Conclusions Our study developed the first nomogram to effectively predict stricture-free survival in patients suffering from ureter stricture after balloon dilation. It is helpful to identify the optimal patients with ureter stricture for balloon dilation and improve treatment outcomes. However, further external validation of the nomogram is warranted.

A Nomogram to Predict Stricture-free Survival in Patients with Ureteral Stricture after Balloon Dilation

Background Balloon dilation is a commonly used minimally invasive endourological treatment of ureteral stricture, but the postoperative recurrence rate is relatively high. And factors contributing to recurrence after treatment are poorly understood. Herein, we sought to develop a novel clinical nomogram to predict ureteral stricture-free survival in patients suffering from ureter stricture and performed balloon dilation. Methods The nomogram was established based on a retrospective analysis of 321 patients diagnosed with ureter strictures from January 2016 to January 2020 in Sun Yat-sen Memorial Hospital using the Cox regression model. Perioperative clinical data and disease outcomes were analyzed. Discrimination of the nomogram was assessed by the concordance index (C-index) and the calibration curve. The results were internally validated using bootstrap resampling. Results Overall, 321 patients with a median follow-up of 590 days were enrolled in the study, among which 97 patients (30.2%) developed recurrence of ureteral stricture during follow-up. Five variables remained significant predictors of ureteral re-stricture after multivariable analyses: stricture nature (P < 0.001), urinary nitrite (P = 0.041), CKD (P = 0.005), stent retention time (P < 0.001), and balloon size (P = 0.029). The calibration craves for the probability of 1-, 3-, and 5-years stricture-free survival (SFS) presented satisfied with the consistency of nomogram prediction and actual observation. The C-index of the model was 0.74 (95% CI 0.70–0.79). Conclusions Our study developed the first nomogram to effectively predict stricture-free survival in patients suffering from ureter stricture after balloon dilation. It is helpful to identify the optimal patients with ureter stricture for balloon dilation and improve treatment outcomes. However, further external validation of the nomogram is warranted.

A robotic pill for oral delivery of biotherapeutics: safety, tolerability, and performance in healthy subjects

Biotherapeutics are highly efficacious, but the pain and inconvenience of chronic injections lead to poor patient compliance and compromise effective disease management. Despite innumerable attempts, oral delivery of biotherapeutics remains unsuccessful due to their degradation in the gastrointestinal (GI) environment and poor intestinal absorption. We have developed an orally ingestible robotic pill (RP) for drug delivery, which protects the biotherapeutic drug payload from digestion in the GI tract and auto-injects it into the wall of the small intestine as a safe, pain-free injection since the intestines are insensate to sharp stimuli. The payload is delivered upon inflation of a balloon folded within the RP, which deflates immediately after drug delivery. Here we present results from two clinical studies demonstrating the safety, tolerability and performance of the RP in healthy humans. In the first study, three versions of the RP (A, B and C) were evaluated, which were identical in all respects except for the diameter of the balloon. The RP successfully delivered a biotherapeutic (octreotide) in 3 out of 12 subjects in group A, 10 out of 20 subjects in group B and 16 out of 20 subjects in group C, with a mean bioavailability of 65 ± 9% (based on successful drug deliveries in groups A and B). Thus, reliability of drug delivery with the RP ranged from 25 to 80%, with success rate directly related to balloon size. In a separate study, the deployment of the RP was unaffected by fed or fasting conditions suggesting that the RP may be taken with or without food. These promising clinical data suggest that biotherapeutics currently administered parenterally may be safely and reliably delivered via this versatile, orally ingestible drug delivery platform. Graphical abstract

Improving pulmonary vein isolation during cryoballoon ablation using the re-look angiography technique

Background Cryoballoon ablation for pulmonary vein (PV) antral isolation is contact-dependent. Currently, occlusion assessment using the cryoballoon is most commonly performed using contrast venogram prior to ablation. However, there is a known difference in balloon size/shape between the inflated and ablation state, due to significant increase in cryoballoon pressure, which can cause potential undetected leak and, thus, failure of PV isolation. This phenomenon is currently not detected using standard techniques and effectiveness of mitigation techniques have not been assessed. Purpose We hypothesize that repeat injection of contrast five seconds after the initiation of cryoballoon ablation can be used to assess changes in shape and confirm ongoing occlusion during ablation; the re-look angiography technique. The incidence of PVI leak and the ability for the relook angiography to remedy the leak is assessed. Methods A total of 125 patients (440 PVs) undergoing cryoballoon ablation (Medtronic Arctic Front Advance Balloon™) were assessed using the re-look angiography technique unless they required occlusion with a segmental approach. Fifteen patients were excluded from contrast use due to renal insufficiency. Results Successful single occlusion was seen in 330 (75%) PVs and the re-look angiography technique was employed in each of those events. In 180 of the 330 (55%) single PV occlusions, a new PV leak undetected during the initial PV angiogram was identified. This prompted repositioning of the balloon to achieve complete PV isolation in 85 of 180 of the PV cases, with 95 of the cases requiring additional segmental ablation to complete full PV isolation. Conclusion A significant amount of insufficient PV antral contact during cryo-ablation may not be detected with conventional single PV angiography and may explain inadequate PV isolation. The re-look angiography technique is a simple tool to confirm robust balloon contact and guide repositioning as well as identify the need for additional segmental ablation. Additional follow up is needed for translation to improved clinical outcomes. Funding Acknowledgement Type of funding source: None

Not only power and energy but also balloon size is correlated with lesion formation in laser ablation model in vitro study

Background Power and total energy were known to correlate with lesion formation during laser balloon ablation for atrial fibrillation. However, it is unclear whether balloon size can influence lesion formation. The aim of this study was to evaluate the impact of balloon size on lesion formation during laser balloon procedure in vitro model. Methods Laser energy was applied to chicken muscles using first generation laser balloon. Laser ablation was performed with different 2 balloon size (18mm and 32mm) using 2 different power settings (12W/20sec and 8.5W/20sec). Forty lesions were evaluated for each setting. We compared maximum lesion width, maximum lesion depth, depth at maximum width and endocardial lesion width between 18mm and 32mm balloon groups at 12W/20sec and 8.5W/20sec, respectively. Results At 8.5W/20sec, inadequate lesion formation to assess lesion size was observed in 1/40 lesion of 18mm balloon group and in 5/40 lesions of 32mm balloon group. Thus, at 8.5W/20sec 18 mm balloon group consisted of 39 lesions and 32 mm balloon group consisted of 35 lesions. At 12W/20sec 18 mm balloon group consisted of 40 lesions and 32 mm balloon group consisted of 40 lesions. At both power settings, maximum lesion depth was larger in 18mm balloon than in 32mm balloon group. At 12W/20sec setting, maximum lesion width and endocardial width were larger in 32mm balloon group than in 18mm balloon group. At 12W/20sec setting, depth at maximum width was smaller in 32mm balloon group than in 18mm balloon group. Lesion morphologies were summarized in a figure. Conclusion Balloon size could affect lesion formation during laser balloon ablation in addition to laser power and energy. Laser ablation lesion were wider but shallower in 32mm balloon group compared with in 18mm balloon group. Funding Acknowledgement Type of funding source: None

A simple experiment on global warming

A simple experiment has been developed to demonstrate the global warming potential of carbon dioxide (CO 2 ) gas in the Earth's atmosphere. A miniature electric resistance heating element was placed inside an inflatable balloon. The balloon was filled with either air or CO 2 . Whereas the CO 2 partial pressure on the earth's atmosphere is approximately 4 × 10 −4 atm, in this experiment, a high partial pressure of CO 2 (1 atm) was used to compensate for the short radiation absorption path in the balloon. The element was heated to approximately 50°C, the power was then switched off and the element's cooling trends in air and in CO 2 were monitored. It took a longer time to cool the heating element back to ambient temperature in CO 2 than in air. It also took longer times to cool the element in larger size balloons and in pressurized balloons when they were filled with CO 2 . To the contrary, the balloon size or pressure made no difference when the balloons were filled with air. A simple mathematical model was developed, and it confirmed that the radiative heat loss from the element decreased significantly in CO 2 . This investigation showed that the cooling rate of an object, with surface temperature akin to temperatures found on Earth, is reduced in a CO 2 -rich atmosphere because of the concomitant lower heat loss to its environment.