One-Year Outcomes of the ROBUST II Study Evaluating the Use of a Drug-Coated Balloon for Treatment of Urethral Stricture

Objective To report 1-year results of the ROBUST II study investigating the safety and efficacy of a paclitaxel-coated balloon for the treatment of recurrent urethral strictures. Methods Subjects were adult men with a single anterior urethral stricture ≤ 3 cm in length and at least 2 prior stricture treatments. After treatment with the Optilume urethral drug-coated balloon (DCB), subjects were followed through 1 year. The primary safety endpoint was the rate of treatment-related serious complications at 90 days post-procedure. Efficacy outcomes included symptomatic assessments, erectile function measured using the International Index of Erectile Function (IIEF), Qmax, and anatomic success. Results Sixteen men with an average of 4.1 prior dilations were treated with the DCB. Anatomic success was achieved at 6 months in 73%. Average IPSS improved from 18.4 to 6.0 at 1 year (P < 0.001). Qmax improved from 6.9 mL/sec to 20.8 mL/sec (P < 0.001). There was no change in IIEF. Four subjects received additional treatment within 1 year. There were no treatment-related serious complications. Conclusions Short-term follow-up of men with urethral stricture treated with the Optilume DCB showed durable anatomic results at 6 months and sustained symptomatic improvement through 1 year. Treatment with the device was safe.

No Mortality Signal With Stellarex Low-Dose Paclitaxel DCB: ILLUMENATE Pivotal 4-Year Outcomes

Background: Paclitaxel-coated balloons have shown safety and efficacy in the short- to intermediate-term; however, long-term data remain limited. Objectives: To report late safety and efficacy outcomes for a low-dose paclitaxel drug-coated balloon (DCB) compared with percutaneous transluminal angioplasty (PTA) in femoropopliteal lesions from a large randomized controlled trial (RCT). Methods: ILLUMENATE Pivotal is a multicenter, single-blind RCT conducted across 43 US and EU centers to examine the safety and efficacy of the Stellarex DCB for the treatment of femoropopliteal disease. Assessments were recorded for all active patients at 36 and 48 months. Vital status of patients formally exited from the study was also collected. Results: Primary patency through 36 months for patients treated with DCB was significantly higher compared with PTA (p=0.016). The primary safety endpoint through 36 months was 77.4% and 72.4%, respectively (p=0.377). Kaplan-Meier analysis indicated that a higher proportion of DCB subjects were event-free compared with PTA at all study visits. The rate of major adverse event (MAE) through 48 months was 32.9% in the DCB group and 37.9% in the PTA group (p=0.428). No differences in the rate of mortality were evident through 48 months of follow-up with 15.6% in the DCB group and 15.2% in the PTA group (p=0.929). Conclusions: Stellarex DCB was associated with significantly higher patency compared with PTA through 3 years with no mortality difference detected through 4 years. The data from the ILLUMENATE Pivotal RCT support the long-term safety and efficacy of the low-dose Stellarex DCB.

Experience of Combined Procedure During Percutaneous Left Atrial Appendage Closure.

Introduction: Percutaneous left atrial appendage closure (LAAC) is an alternative to oral anticoagulant (OAC) in patients with non-valvular atrial fibrillation (AF) and contraindication to long-term OAC. Combined strategy with percutaneous LAAC at the same time of other cardiac structural or electrophysiological procedure has emerged as an alternative to staged strategy. Aim: To describe our experience of combined LAAC procedures using Watchman™ devices. Method: All patients with combined LAAC procedure using Watchman™ (WN) devices performed from 2016-2021 were included. The primary safety endpoint was a composite of periprocedural complications and adverse events during follow-up. The primary efficacy endpoint included strokes, systemic embolisms, major bleeding, and cardiovascular death. Results: Since 2016, among the 157 patients who underwent LAAC using WN devices, 16 underwent a combined strategy: 6 TEMVR (37%), 6 typical atrial flutter ablation (37%), 2 LP implantation (13%) and 2 atrial fibrillation ablation (13%). The WN device was successfully implanted in 98% and 100% for single and combined LAAC respectively (p = 0.63). Median follow-up was 13 months (IQR 25/75 3/24) in the whole cohort. Device related complications occurred in 6 out of 141 patients (4%) who underwent single LAAC and in no (0/16) patient in the combined LAAC procedure (p=ns). The procedural related complications did not differ significantly between groups (5% vs 12%, respectively in the single and combined group, p=0.1). Conclusion: Combined procedure combining LAAC using the Watchman™ devices and one other structural or electrophysiological procedure is safe and effective. Larger series are needed to confirm these results.

Monitoring the Effectiveness and Safety of ARNI vs. Angiotensin Receptor Blocker by Frailty Status

Using Medicare data 2015-2017, we conducted 5 sequential 1-to-1 propensity score-matched analyses of ARNI initiators and angiotensin receptor blockers (ARB) initiators, mimicking the accrual of new data every 6 months. Primary effectiveness endpoint was a composite of heart failure hospitalization or all-cause mortality and primary safety endpoint was a composite of hospitalization or emergency department visits for hypotension, acute kidney injury, hyperkalemia, and angioedema. Among non-frail patients (n=5,014), the rates (per 100 person-years) for ARNI vs ARB were 12.7 and 9.2 (rate difference: 3.4, 95% CI: 0.8 to 6.1), respectively, for the effectiveness endpoint and 5.2 and 3.6 (rate difference: 1.5, 95% CI: -0.1 to 3.2), respectively, for the safety endpoint. Among frail patients (n=2,694), the corresponding rates were 19.8 and 21.6 (rate difference: -1.8, 95% CI: -7.0 to 3.4) for the effectiveness endpoint and 10.9 and 8.0 (rate difference: 2.9, 95% CI: -0.6 to 6.4) for the safety endpoint.

Randomised controlled trial to investigate optimal antithrombotic therapy in patients with non-valvular atrial fibrillation undergoing percutaneous coronary intervention: a study protocol of the OPTIMA-AF trial

IntroductionThe optimal antithrombotic strategy for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) is uncertain. For patients with non-AF, many trials are now evaluating short 1-month dual antiplatelet therapy. In patients with AF undergoing PCI, in contrast, short dual therapy (P2Y12 inhibitor +direct oral anticoagulant (DOAC)) has not yet been evaluated.Methods and analysisThe OPTIMA-AF trial (OPTIMAl antiplatelet therapy in combination with direct oral anticoagulants in patients with non-valvular Atrial Fibrillation undergoing percutaneous coronary intervention with everolimus-eluting stent) is an investigator-initiated, open-label, nationwide, multicentre, prospective, randomised controlled trial. The primary objective is to compare the efficacy and safety of short dual therapy (1-month DOAC +P2Y12 inhibitor followed by DOAC monotherapy) against long dual therapy (12-month DOAC +P2Y12 inhibitor followed by DOAC monotherapy) in the treatment of AF subjects undergoing PCI. The primary efficacy endpoint is a composite of death or thromboembolic events (myocardial infarction, definite stent thrombosis, stroke or systemic embolism) at 365 days; and the primary safety endpoint is bleeding (International Society on Thrombosis and Haemostasis major or clinically relevant non-major bleeding) at 365 days. This trial is intended to show the non-inferiority of short dual therapy versus long dual therapy in terms of the primary efficacy endpoint and show superiority in terms of the primary safety endpoint. A total of 1090 subjects will be randomised in a 1:1 ratio at approximately 60 sites.Ethics and disseminationThis study received approval from the Certified Review Board of Osaka University (a certified research ethics committee by the Japanese Clinical Research Act). The findings will be disseminated through peer-reviewed publications and conference presentations.Trial registration numberJapan Registry of Clinical Trials: jRCTs051190053; Pre-results.

Diversion-p64: results from an international, prospective, multicenter, single-arm post-market study to assess the safety and effectiveness of the p64 flow modulation device

BackgroundThe use of flow diversion to treat intracranial aneurysms has increased in recent years.ObjectiveTo assess the safety and angiographic efficacy of the p64 flow modulation device.MethodsDiversion-p64 is an international, prospective, multicenter, single-arm, study conducted at 26 centers. The p64 flow modulation device was used to treat anterior circulation aneurysms between December 2015 and January 2019. The primary safety endpoint was the incidence of major stroke or neurologic death at 3–6 months, with the primary efficacy endpoint being complete aneurysm occlusion (Raymond-Roy Occlusion Classification 1) on follow-up angiography.ResultsA total of 420 patients met the eligibility criteria and underwent treatment with the p64 flow modulation device (mean age 55±12.0 years, 86.2% female). Mean aneurysm dome width was 6.99±5.28 mm and neck width 4.47±2.28 mm. Mean number of devices implanted per patient was 1.06±0.47, with adjunctive coiling performed in 14.0% of the cases. At the second angiographic follow-up (mean 375±73 days), available for 343 patients (81.7%), complete aneurysm occlusion was seen in 287 (83.7%) patients. Safety data were available for 413 patients (98.3%) at the first follow-up (mean 145±43 days) with a composite morbidity/mortality rate of 2.42% (n=10).ConclusionsDiversion-p64 is the largest prospective study using the p64 flow modulation device. The results of this study demonstrate that the device has a high efficacy and carries a low rate of mortality and permanent morbidity.

1108. Evaluation of Vancomycin Dosing in Adolescents

Background Pediatric vancomycin dosing varies based on age and renal function. Recent literature suggests previously recommended doses of 45-60 mg/kg/day may be insufficient to achieve an AUC:MIC ratio of 400-600 mg-hr/L and higher doses of at least 60 mg/kg/day may be required. However, data to guide dosing in adolescents is limited. Methods A single-center, retrospective chart review of patients aged 12 to 18 years who received vancomycin and had therapeutic drug monitoring (TDM) performed between July 2017 to June 2020 were included. The primary endpoint was the median total daily dose (TDD) of vancomycin required to achieve therapeutic serum concentrations. Secondary endpoints were to characterize how factors such as age, weight, trough versus AUC monitoring, malignancy, and trauma may influence dosing. The safety endpoint was the development of acute kidney injury (AKI). Results 130 vancomycin courses in 86 patients were included. Baseline characteristics are presented in Table 1. Of the 130 vancomycin courses, 50 courses (38%) achieved therapeutic serum concentrations at a median TDD of 49.8 mg/kg/day (IQR 42 – 59.4). This was not statistically different from the sub- or supra-therapeutic groups (p=0.22). Based on age, the median TDD for 12-14 year olds was higher at 60 mg/kg/day (IQR 45-78.8; n=14) than for 15-16 and 17-18 year olds [45.3 mg/kg/day (IQR 41.1-51; n=15), 48 mg/kg/day (IQR 42-52; n=21), respectively]. Obese patients needed a median TDD of 43.5 mg/kg/day vs at least 51 mg/kg/day in healthy and overweight patients. Finally, AUC guided dosing resulted in a slightly lower overall median TDD vs trough guided dosing (45.8 mg/kg/day vs 50.5 mg/kg/day). Additional dose requirements based on age, weight, TDM and other characteristics are presented in Table 2. Of the 15 patients who developed AKI per pRIFILE criteria, 2 were classified as injury and 3 as failure. Table 2. Total Daily Dose Course Analysis Conclusion To achieve therapeutic levels, adolescents 12 to14 years old need higher empiric doses of 60 mg/kg/day compared to 45 mg/kg/day in 15 to 18 year olds. Obese patients, however, may require lower TDD than underweight, healthy, and overweight patients. Patients that receive AUC versus trough monitoring may also require lower TDD to achieve therapeutic concentrations. More data is needed to further evaluate our findings. Disclosures All Authors: No reported disclosures

Outcomes and Hemodynamic Performances of Transcatheter Aortic Valve Replacement With Two Generations of Self-expanding Transcatheter Aortic Valves

The aim of this study was to investigate the hemodynamic and clinical performance of the Evolut R compared with its direct predecessor, CoreValve, in Taiwanese population. This study included all consecutive patients who underwent TAVR with either the CoreValve or Evolut R between March 2013 to December 2020. Thirty-day Valve Academic Research Consortium-2 (VARC-2)-defined outcomes and hemodynamic performances were investigated. There were no significant differences in baseline demographic characteristics between patients receiving CoreValve (n= 117) or Evolut R (n=117). Aortic valve-in-valve procedures for failed surgical bioprosthesis and procedures under conscious sedation were performed significantly more often with Evolut R. Pre-dilatation was performed significantly more often and contrast media volume was significantly higher with CoreValve. Stroke (0% vs 4.3%, p = 0.024) and the need for emergent conversion to open surgery (0% vs 5.1%, P = 0.012) were significantly lower in Evolut R than CoreValve recipients. Evolut R significantly reduce 30-day composite safety endpoint (4.3% vs 15.4%, p = 0.004). In conclusion, advancements in transcatheter valve technologies have resulted in improved outcomes for patients undergoing TAVR with self-expanding valves. With new-generation Evolut R, device success was high and significantly reduced 30-day composite safety endpoint after TAVR compared with CoreValve.

Post-ST-Segment Elevation Myocardial Infarction Follow-Up Care During the COVID-19 Pandemic and the Possible Benefit of Telemedicine: An Observational Study

Background: Infectious control measures during the COVID-19 pandemic have led to the propensity toward telemedicine. This study examined the impact of telemedicine during the pandemic on the long-term outcomes of ST-segment elevation myocardial infarction (STEMI) patients.Methods: This study included 288 patients admitted 1 year before the pandemic (October 2018–December 2018) and during the pandemic (January 2020–March 2020) eras, and survived their index STEMI admission. The follow-up period was 1 year. One-year primary safety endpoint was all-cause mortality. Secondary safety endpoints were cardiac readmissions for unplanned revascularisation, non-fatal myocardial infarction, heart failure, arrythmia, unstable angina. Major adverse cardiovascular events (MACE) was defined as the composite outcome of each individual safety endpoint.Results: Despite unfavorable in-hospital outcomes among patients admitted during the pandemic compared to pre-pandemic era, both groups had similar 1-year all-cause mortality (11.2 vs. 8.5%, respectively, p = 0.454) but higher cardiac-related (14.1 vs. 5.1%, p &lt; 0.001) and heart failure readmissions in the pandemic vs. pre-pandemic groups (7.1 vs. 1.7%, p = 0.037). Follow-up was more frequently conducted via teleconsultations (1.2 vs. 0.2 per patient/year, p = 0.001), with reduction in physical consultations (2.1 vs. 2.6 per patient/year, p = 0.043), during the pandemic vs. pre-pandemic era. Majority achieved guideline-directed medical therapy (GDMT) during pandemic vs. pre-pandemic era (75.9 vs. 61.6%, p = 0.010). Multivariable Cox regression demonstrated achieving medication target doses (HR 0.387, 95% CI 0.164–0.915, p = 0.031) and GDMT (HR 0.271, 95% CI 0.134–0.548, p &lt; 0.001) were independent predictors of lower 1-year MACE after adjustment.Conclusion: The pandemic has led to the wider application of teleconsultation, with increased adherence to GDMT, enhanced medication target dosing. Achieving GDMT was associated with favorable long-term prognosis.

Endovascular renal sympathetic denervation to improve heart failure with reduced ejection fraction: the IMPROVE-HF-I study

Introduction The aim of the present study was to assess the safety and efficacy of renal sympathetic denervation (RDN) in patients with heart failure with reduced ejection fraction (HFrEF). Methods We randomly assigned 50 patients with a left ventricular ejection fraction (LVEF) ≤ 35% and NYHA class ≥ II, in a 1:1 ratio, to either RDN and optimal medical therapy (OMT) or OMT alone. The primary safety endpoint was the occurrence of a combined endpoint of cardiovascular death, rehospitalisation for heart failure, and acute kidney injury at 6 months. The primary efficacy endpoint was the change in iodine-123 meta-iodobenzylguanidine (123I‑MIBG) heart-to-mediastinum ratio (HMR) at 6 months. Results Mean age was 60 ± 9 years, 86% was male and mean LVEF was 33 ± 8%. At 6 months, the primary safety endpoint occurred in 8.3% vs 8.0% in the RDN and OMT groups, respectively (p = 0.97). At 6 months, the mean change in late HMR was −0.02 (95% CI: −0.08 to 0.12) in the RDN group, versus −0.02 (95% CI: −0.09 to 0.12) in the OMT group (p = 0.95) whereas the mean change in washout rate was 2.34 (95% CI: −6.35 to 1.67) in the RDN group versus −2.59 (95% CI: −1.61 to 6.79) in the OMT group (p-value 0.09). Conclusion RDN with the Vessix system in patients with HFrEF was safe, but did not result in significant changes in cardiac sympathetic nerve activity at 6 months as measured using 123I‑MIBG.