Real-world Registry Research Articles

Safe implementation of surgical innovation: a prospective registry of the Versius Robotic Surgical System

ObjectivesTo describe a new, international, prospective surgical registry developed to accompany the clinical implementation of the Versius Robotic Surgical System by accumulating real-world evidence of its safety and effectiveness.InterventionsThis robotic...

Abstract 28: First Pass Outcomes And Associated Clot Characteristics: Secondary Analysis Of The Excellent Registry

Introduction: EXCELLENT (NCT03685578) is a global prospective, multicenter, real-world registry of mechanical thrombectomy for stroke with the EmboTrap device as first line treatment which includes clot collection and analysis. Aim of the study: To report the rates of clinical outcomes and clot characteristics associated with first pass reperfusion in EXCELLENT. Methods: Per pass angiographic outcomes assessed by an independent core lab were available in 984 subjects Analysis of clot from 538 cases was performed by independent central labs blinded to clinical data. 90-day mRS assessment was blinded to subject data. Results: First pass reperfusion of mTICI 2b-3 (63.2%) and 2c-3 (38.3%) was significantly predictive of mRS 0-2 or ≤pre-stroke (p=0.011 and p=0.016) but not all-cause mortality at 90 days (p=0.080 and p=0.123, respectively). Further, mTICI 2c-3 in one pass was associated with a higher rate of mRS 0-2 or ≤pre-stroke vs. mTICI 2c-3 reperfusion in >1 pass, (55.5% and 45.1%, respectively, p=0.013) and a rate of all-cause mortality at 90 days of 14.6% vs. 19.8% (p=0.097). Full patient characteristics and clinical outcomes are shown in Table 1. Notable clot composition findings included: RBC (%, mean±SD): mTICI 2c-3, 1 pass 47.69±22.25, mTICI 2c-3, >1 pass 43.86±19.05, (p=0.088); fibrin: mTICI 2c-3, 1 pass 23.20±13.80, mTICI 2c-3 >1 pass 25.40 ± 13.52 (p=0.131); von Willebrand factor (VWF): mTICI2c-3, 1 pass 16.09±14.62, mTICI 2c-3, >1 pass 19.42±17.15 (p=0.038). Conclusions: First pass reperfusion in the EXCELLENT registry was associated with better clinical outcomes at 90 days. Clots retrieved with first pass reperfusion had higher RBC and lower fibrin and VWF content compared to those who achieved reperfusion at greater than one pass.

OP36 Real-world evidence on comparative effectiveness of Ustekinumab vs anti-TNF in Crohn’s disease with propensity score adjustment: two-year maintenance phase results from the prospective observational RUN-CD study

Abstract Background Within the framework of the prospective real-world RUN-CD registry on the effectiveness and safety of ustekinumab (UST) in Crohn’s disease (CD), a total of 901 CD-patients undergoing a newly initiated biologics therapy were enrolled in 44 IBD-experienced centers from all over Germany between 2017-2020 with a follow-up of 3 years. Here, the results on the effectiveness of the maintenance therapy over 24 months are presented as a real-world evidence (RWE) comparison of CD-patients with UST vs anti-TNF. Methods After exclusion of other biologics than UST and anti-TNF and missing outcomes (HBI), the final sample consisted of 550 CD patients. Clinical remission (HBI ≤ 4) was the predefined endpoint at month 24 and additionally, switching of biologics therapy was considered as an outcome failure. Patients were analysed on a modified intent-to-treat basis (mITT; switchers considered as outcome failure). To reduce the effect of confounders, propensity score (PS) adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used, and the results were reported as odds ratio (OR) and 95% confidence interval (CI). Quality of life was assessed using the self-reported visual analogue scale (EQ-VAS) of the EQ-5D with changes from baseline to 2 years. Results 308 UST (naïve: 27) and 242 anti-TNF (naïve: 162) CD-patients were included (ADA: 61.2%, IFX: 38.8%). The number of switches within 24 months was significantly lower with UST than with anti-TNF (27.6% vs 37.1%; p=0.038), and especially with IFX, whereby the difference between UST and IFX (27.6% vs 46.7%; p=0.003) proves to be statistically significant (Fig. 1). Clinical remission at two years was not statistically different for the overall UST vs anti-TNF groups (51.2% vs 54.4) (numerically higher in biologic-naïve UST- vs anti-TNF-patients, without statistically significance) (Tab. 1). Remission rates were similar for UST vs ADA, while they were significantly higher for UST vs IFX (54.4% vs 37.9%; p=0.008) (Tab. 2), and also significantly higher for ADA vs. IFX (58.2% vs 37.9%; p=0.003). As a sign of an improved QoL we observed a significant increase in EQ-VAS within both treatment groups. However, a similar increase in EQ-VAS was observed with UST and anti-TNF (+14.2 vs +12.3; p=0.147). Conclusion In this prospective two-year RWE comparison clinical remission was, also due to more frequent switches within the IFX group, significantly higher with UST when compared with IFX and higher with ADA than with IFX. Considering the effectiveness results of UST and the proven favourable safety profile, UST can be considered a first-line targeted therapy for CD.

P656 Superior treatment persistence with ustekinumab in biologic-experienced luminal Crohn’s disease: real-world registry data from the Persistence Australian National IBD Cohort (PANIC) study

Abstract Background Ustekinumab has been shown equivalent to adalimumab in the treatment of biologic-naïve patients with Crohn’s disease (CD) at 1 year. However the real world persistence of these medications, and particularly when used sequentially in biologic-experienced patients is unknown. Prescription data provides real-world evidence about treatment efficacy, tolerability and prescriber and patient acceptability. Methods Persistent of medication was analysed from the Australian Pharmaceutical Benefits Scheme (PBS) registry data 2005-2019 for luminal Crohn’s disease, using a 10% representative sample. Results There were 2029 patients over the 15 year period with 5618 years of patient follow up. The median age was 43 years (interquartile range (IQR): 34-58), with 891/2029 (43.9%) male. Via therapy, 915/2029 (45.1%) were on adalimumab, 722/2029 (35.6%) were on infliximab 155/2029 (7.6%) were on vedolizumab, and 237/2029 (11.7%) were on ustekinumab. Used as a first-line biologic (bio-naïve), there was no difference between any agent for persistence (p>0.05). Used after first-line (bio-experienced), ustekinumab had significantly better persistence than TNFa inhibitors (TNFi) (p= 0.006) and vedolizumab (p<0.001), additionally vedolizumab had poorer persistence than TNFi (p=0.028). In bio-experienced patients, ustekinumab persistence was greater than non-ustekinumab biologic agents (p= 0.0018). TNFi persistence was significantly poorer in bio-experienced vs naïve patients (p=0.042), with a non-significant trend for poorer outcomes in vedolizumab (p= 0.059), but did not differ for ustekinumab (p=0.509). Used after a TNFi agent, ustekinumab had superior persistence to an alternative TNFi agent (p=0.033). Using a propensity score matched analysis for age, immunomodulator use and line of therapy, ustekinumab had superior to persistence to non-ustekinumab agents (p=0.0044) and to TNFi (p=0.01). Multivariate predictors of loss of persistence were biologic used (adjusted hazard ratios (aHR): 0.84, p=0.001), and line of therapy (aHR: 1.16, p=0.003). Conclusion The PANIC cohort with real-world data of non-hierarchical prescribing of biological agents does not support the superiority of any agent in biologic-naïve luminal CD. However for biologic experienced, the persistence is greater with ustekinumab than TNFa inhibitors, and vedolizumab persistence is significantly poorest. These findings will assist in the positioning of biological therapies in luminal CD.

Real-world comparison of intracoronary imaging and fractional flow reserve measurements on outcomes of semi-urgent and elective percutaneous coronary intervention in a multi-ethnic asian population

Abstract Funding Acknowledgements Type of funding sources: None. Background Intracoronary imaging and fractional flow reserve measurements (FFR) are helpful in optimisation of percutaneous coronary intervention (PCI) for patients with stable coronary artery disease, but their comparative efficacy is not well described. Furthermore, few studies involve Asian patients in a real-world context. Purpose This study aims to compare the use of intracoronary imaging and fractional flow reserve measurements on the outcomes of semi-urgent and elective PCI in a multi-ethnic Asian population. Methods This was a retrospective database study of patients who underwent semi-urgent and elective PCI from 1st Jan 2014 to 31st Dec 2015 at a tertiary academic centre. The patients were split into 2 groups – imaging-guided (IG) consisting of intravascular ultrasound guided PCI or optical coherence tomography guided PCI and physiology-guided (PG) which included FFR-guided PCI. Patients who underwent both IG PCI and PG PCI were excluded. Incidence rates of major adverse cardiovascular events (MACE) (Subsequent myocardial infarction, congestive cardiac failure, all-cause mortality) and major adverse cardiovascular and cerebrovascular events (MACCE) (Subsequent myocardial infarction, congestive cardiac failure, stroke or transient ischemic attack and all-cause mortality) were compared between the two groups. One-to-one propensity score matching (PSM) was performed to control for potential bias. Results Of 1,732 patients studied, the median age was 61.0 years (IQR 53.0 to 68.0) and 336 were female (19.4%). There were 266 patients (15.4%) in IG and 186 (10.7%) in PG. The patients were followed up for 33 ±37 months. A total of 133 pairs were matched. In the unmatched cohort, there was no statistical difference between the IG and PG group in the incidence of MACE (24.2% vs 15.5%, p= 0.099) and MACCE (26.6% vs 17.7%, p= 0.112). Baseline and procedural characteristics were balanced between the IG and PG groups. In the matched cohort, the incidence rates of MACE (11.3% vs 7.5%, p= 0.383) and MACCE (15.8% vs 12.8%, p=0.596) did not differ significantly between the two groups. Conclusion In a real-world multi-ethnic Asian registry of semi-urgent and elective PCI patients, there was no difference in outcomes whether patients underwent the use of intracoronary imaging or fractional flow reserve measurements during PCI.

Left atrial appendage closure in end-stage renal disease and hemodialysis: Data from a German multicenter registry.

Left atrial appendage closure (LAAC) has emerged as an alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF). OAC treatment has been proven feasible in mild-to-moderate chronic kidney disease (CKD). In contrast, the optimal antithrombotic management of AF patients with end-stage renal disease (ESRD) is unknown and LAAC has not been proven in these patients in prospective randomized clinical trials. The objective of this study is to evaluate safety and efficacy of LAAC in patients with ESRD. Patients undergoing LAAC were collected in a German multicenter real-world observational registry. A composite endpoint consisting of the occurrence of ischemic stroke/transient ischemic attack, systemic embolism, and/or major clinical bleeding was assessed. Patients with ESRD were compared with propensity score-matched patients without severe CKD. ESRD was defined as a glomerular filtration rate < 15 ml/min/1.73 m2 or chronic hemodialysis treatment. A total of 604 patients were analyzed, including 57 with ESRD and 57 propensity-matched patients. Overall, 596 endocardial and 8 epicardial LAAC procedures were performed. Frequency of major complications was 7.0% (42/604 patients) in the overall cohort, 8.8% (5/57 patients) in patients with ESRD, and 10.5% (6/57 patients) in matched controls (p = 0.75). The estimated event-free survival of the combined endpoint after 500 days was 90.7 ± 4.5% in patients with ESRD and 90.2 ± 5.5% in matched controls (p = 0.33). LAAC had comparable procedural safety and clinical efficacy in patients with ESRD and patients without severe CKD.

Racial and ethnic disparities in a real-world precision oncology data registry

Biorepositories enable precision oncology research by sharing clinically annotated genomic data, but it remains unknown whether these data registries reflect the true distribution of cancers in racial and ethnic minorities. Our analysis of Project Genomics Evidence Neoplasia Information Exchange (GENIE), a real-world cancer data registry designed to accelerate precision oncology discovery, indicates that minorities do not have sufficient representation, which may impact the validity of studies directly comparing mutational profiles between racial/ethnic groups and limit generalizability of biomarker discoveries to all populations.

Patent foramen ovale occlusion with the Cocoon PFO Occluder. The PROS-IT collaborative project.

The Cocoon patent foramen ovale (PFO) Occluder is a new generation nitinol alloy double-disk device coated with nanoplatinum, likely useful in patients with nickel hypersensitivity. Early results and mid-term outcomes of this device in percutaneous PFO closure are missing. To assess the preliminary efficacy and safety profile of PFO closure with Cocoon device in an Italian multi-center registry. This is a prospective registry of 189 consecutive adult patients treated with the Cocoon PFO Occluder at 15 Italian centers from May 2017 till May 2020. Patients were followed up for 2 years. Closure of the PFO with Cocoon Occluder was carried out successfully in all patients, with complete closure without residual shunt in 94.7% of the patients and minimal shunt in 5.3%. Except from a case of paroxysmal supraventricular tachycardia and a major vascular bleeding, no procedural and in-hospital device-related complications occurred. No patient developed cardiac erosions, allergic reactions to nickel, or any other major complications during the follow-up. During the follow-up period, 2 cases of new-onset atrial fibrillation occurred within thirty-day. Percutaneous closure of PFO with Cocoon Occluder provided satisfactory procedural and mid-term clinical follow-up results in a real-world registry.

Treatment strategies in patients with gynecological sarcoma: Results of the prospective intergroup real-world registry for gynecological sarcoma in Germany (REGSA-NOGGO RU1)

ObjectiveGynecological sarcomas account for 3% of all gynecological malignancies and are associated with a poor prognosis. Due to the rarity and heterogeneity of gynecological sarcomas there is still no consensus...

Real-world evidence of switching P2Y12 receptor–inhibiting therapies to prasugrel after PCI in patients with ACS: results from EFF-K registry

BackgroundPotent P2Y12 inhibitors are recommended for up to 12 months after percutaneous coronary intervention (PCI) in patients diagnosed with acute coronary syndrome (ACS). However, the prescription pattern is diverse in real world practice, which includes various switching between antiplatelet regimens. In this study, we analyzed the prescription patterns of prasugrel, and assessed the safety and effectiveness of P2Y12 inhibitors switching patterns in a real world registry of patients subjected to PCI after ACS.MethodsThe EFF-K study included 3077 ACS patients receiving prasugrel-based dual antiplatelet therapy. The cohort was divided into those who were administered with prasugrel as the primary antiplatelet treatment (naïve cohort) or as a substitute agent after clopidogrel or ticagrelor pre-treatment (switch cohort). The primary endpoint was a net adverse clinical event (NACE; a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or TIMI major bleeding unrelated to coronary-artery bypass grafting).ResultsA total of 3077 patients diagnosed with ACS were included in the analysis. Among the total population, 726 patients (23.6%) were classed as the naïve cohort and 2351 patients (76.4%) as the switch cohort. Baseline characteristics showed that the switch cohort had more comorbidities, such as hypertension, diabetes mellitus, heart failure and previous PCI. The major cause of switching to prasugrel in the switch cohort was the necessity for a more potent antiplatelet agent (56.3%). During a 12-month follow-up period, 51 patients (1.7%) experienced at least one NACE. The incidence of NACE did not differ between the naïve and switch cohort (1.5% vs. 1.7%, Hazard ratio 1.17, 95% Confidence interval 0.56–2.43, P = 0.677). In subgroup analysis, no significant interaction was observed between the treatment strategy and the incidence of NACE across various subgroups.ConclusionsDual antiplatelet therapy with prasugrel seems to be safe and effective both as a primary treatment and as a substitute for other P2Y12 inhibitors in a real world registry of Asian ACS patients receiving PCI.Trial registration: KCT0002356, registered June 13, 2017.

Automation of Hematopoietic Cell Transplantation Outcomes Reporting Leads to Dramatic Reduction in Errors Reported to Real-World Data Registry

Institutions that perform hematopoietic cell transplantation (HCT) are required by law to report standardized, structured data on transplantation outcomes. A key post-transplantation outcome is engraftment, the time between HCT infusion and reemergence of circulating neutrophils and platelets. At our center, we found that manual chart abstraction for engraftment data was highly error-prone. We developed a custom R/Shiny application that automatically calculates engraftment dates and displays them in an intuitive format to augment the manual chart review. Our hypothesis was that use of the application to assist with calculating and reporting engraftment dates would be associated with a decreased error rate. The study was conducted at a single tertiary care institution. The application was developed in a collaborative, multidisciplinary fashion by members of an embedded cellular therapy informatics team. Retrospective validation of the application's accuracy was conducted on all malignant HCTs from February 2016 to December 2020 (n=198). Real-world use of the application was evaluated prospectively from April 2021 through April 2022 (n=53). The Welch 2-sample t test was used to compare error rates preimplementation and postimplementation. Data were visualized using p charts, and standard special cause variation rules were applied. The accuracy of reported data postdeployment increased dramatically; the engraftment error rate decreased from 15% to 3.8% for neutrophils (P=.003) and from 28% to 1.9% for platelets (P < .001). This study demonstrates the effective deployment of a custom R/Shiny application that was associated with significantly reduced error rates in HCT engraftment reporting for operational, research, and regulatory purposes. Users reported subjective satisfaction with the application and that it addressed difficulties with the legacy manual process. Identifying and correcting erroneous data in engraftment reporting could lead to a more efficient and accurate nationwide assessment of transplantation success. Furthermore, we show that it is possible and practical for academic medical centers to create and support embedded informatics teams that can quickly build applications for clinical operations in a manner compliant with regulatory requirements.

Real-World Examination of Revascularization Strategies for Left Main Coronary Disease in Ontario, Canada

BackgroundRandomized trials have compared percutaneous coronary intervention and coronary artery bypass grafting (CABG) in patients with left main coronary artery disease undergoing nonemergent revascularization. However, there is a paucity of real-world contemporary observational studies comparing percutaneous coronary intervention (PCI) and CABG. ObjectivesThe purpose of this study was to compare the long-term clinical outcomes of CABG versus PCI in patients with left main coronary disease. MethodsClinical and administrative databases for Ontario, Canada, were linked to obtain records of all patients with angiographic evidence of left main coronary artery disease (≥50% stenosis) treated with either isolated CABG or PCI from 2008 to 2020. Emergent, cardiogenic shock, and ST-segment elevation myocardial infarction patients were excluded. Baseline characteristics of patients were compared and 1:1 propensity score matching was performed. Late mortality and major adverse cardiac and cerebrovascular events were compared between the matched groups using a Cox proportional hazard model. ResultsAfter exclusions, 1,299 and 21,287 patients underwent PCI and CABG, respectively. Prior to matching, PCI patients were older (age 75.2 vs 68.0 years) and more likely to be women (34.6% vs 20.1%), although they had less CAD burden. Propensity score matching on 25 baseline covariates yielded 1,128 well-matched pairs. There was no difference in early mortality between PCI and CABG (5.5% vs 3.9%; P = 0.075). Over 7-year follow-up, all-cause mortality (53.6% vs 35.2%; HR: 1.63; 95% CI: 1.42-1.87; P < 0.001) and major adverse cardiac and cerebrovascular events (66.8% vs 48.6%; HR: 1.77; 95% CI: 1.57-2.00) were significantly higher with PCI than CABG. ConclusionsCABG was the most common revascularization strategy in this real-world registry. Patients undergoing PCI were much older and of higher risk at baseline. After matching, there was no difference in early mortality but improved late survival and freedom from major adverse cardiac and cerebrovascular events with CABG.

RCT versus real-world cohorts: Differences in patient characteristics drive associations with outcome after EVT.

The selection of patients with large-vessel occlusion (LVO) stroke for endovascular treatment (EVT) depends on patient characteristics and procedural metrics. The relation of these variables to functional outcome after EVT has been assessed in numerous datasets from both randomized controlled trials (RCT) and real-world registries, but whether differences in their case mix modulate outcome prediction is unknown. We leveraged data from individual patients with anterior LVO stroke treated with EVT from completed RCTs from the Virtual International Stroke Trials Archive (N = 479) and from the German Stroke Registry (N = 4079). Cohorts were compared regarding (i) patient characteristics and procedural pre-EVT metrics, (ii) these variables' relation to functional outcome, and (iii) the performance of derived outcome prediction models. Relation to outcome (functional dependence defined by a modified Rankin Scale score of 3-6 at 90 days) was analyzed by logistic regression models and a machine learning algorithm. Ten out of 11 analyzed baseline variables differed between the RCT and real-world cohort: RCT patients were younger, had higher admission NIHSS scores, and received thrombolysis more often (all p < 0.0001). Largest differences at the level of individual outcome predictors were observed for age (RCT: adjusted odds ratio (aOR), 1.29 (95% CI, 1.10-1.53) vs real-world aOR, 1.65 (95% CI, 1.54-1.78) per 10-year increments, p < 0.001). Treatment with intravenous thrombolysis was not significantly associated with functional outcome in the RCT cohort (aOR, 1.64 (95 % CI, 0.91-3.00)), but in the real-world cohort (aOR, 0.81 (95% CI, 0.69-0.96); p for cohort heterogeneity = 0.056). Outcome prediction was more accurate when constructing and testing the model using real-world data compared to construction with RCT data and testing on real-world data (area under the curve, 0.82 (95% CI, 0.79-0.85) vs 0.79 (95% CI, 0.77-0.80), p = 0.004). RCT and real-world cohorts considerably differ in patient characteristics, individual outcome predictor strength, and overall outcome prediction model performance.

89 GUIDE EXTENSION CATHETER: INDICATION, USE AND RESULTS IN A LARGE SERIES OF COMPLEX PERCUTANEOUS CORONARY INTERVENTIONS

Abstract Aims The guide extension catheter (GEC) is a helpful tool to increase catheter support when facing complex percutaneous coronary intervention (PCI) in unfavorable coronary anatomies. The aim of this study was to describe indication, efficacy, and safety of the GEC in a high-volume center. Methods and results From 2014 to 2021, we retrospectively identified and analyzed 351 interventional cases in which GEC was used to complete the procedure. The endpoints of the study were PCI success, procedural success and device failure. GEC use increased over the years and was more frequently used by radial approach (92.1%) in elective setting (90.6%) and using the 6F size (95.3%). The GEC was mostly implemented as bail-out strategy (75.9%) with the aim to improve back-up (89.6%), less frequently to optimize catheter alignment or obtain selective coronary cannulation (10.4%). Intracoronary advancement was performed using the guidewire in 1.3% of cases, after positioning of a second “buddy” wire in 23.2%, with support of a deflated balloon at the distal tip in 12.2%, or with anchoring technique in 63.3%. Mean coronary deep intubation depth was 38.8±23.9mm. Vessel and lesion characteristics are reported in Table I. Overall, PCI success rate was 92.5%, while procedural success (PCI success without in hospital adverse event) was 88.6%. GEC was successfully used in 92.7% of patients with no device-dependent severe adverse events; in particular, failures were related to inability to cross the target lesion in 4.5% or to device–related complication in 2.85% of cases. Conclusions This large real-world registry on GEC use in complex PCI confirms the GEC as a valid and safe tool to increase backup support and overcome the limits of conventional technique during complex PCI.

432 SACUBITRIL/VALSARTAN AND RISK OF SUPRAVENTRICULAR ARRHYTHMIAS AS DETECTED BY REMOTE MONITORING IN HEART FAILURE PATIENTS

Abstract Introduction Sacubitril/valsartan (ARNI) has demonstrated a significant benefit compared to angiotensin inhibitor (enalapril) in decreasing both morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF). While. recent studies demonstrated that in HFrEF patients, ARNI decreased ventricular arrhythmias no data is available with regards to the supraventricular arrhythmic burden in HFrEF patients with an implantable cardioverter defibrillator (ICD) or cardiac resynchronisation therapy-defibrillator (CRT-D) and remote monitoring. The aim of out study was to assess if ARNI therapy was able to significantly reduce supraventricular arrhythmias. More specifically the primary endpoint was the incidence of AT/AF episodes, as detected by the device. Secondary endpoints included the total burden of AT/AF, the mean number of premature ventricular contractions (PVC) per hour and the percentage of biventricular pacing per day (in patients with CRT-D). Methods We conducted a multicentre, observational, prospective registry : the SAVE THE RHYTHM (SAacubitril Valsartan rEal-world registry evaluating THE arRHYTHMia burden in HFrEF patients with implantable cardioverter defibrillator). We enrolled all patients with HFrEF, ICD or CRT-D actively followed through remote monitoring and starting treatment with sacubitril/valsartan. All patients were followed-up for at least one year. Results At the end of enrollment, 265 patients from 5 centres had at least one sacubitril/valsartan prescription (88% males, age 68±10 years). The annual incidence of AT/AF episodes decreased from 16.6% before sacubitril/valsartan to 12.8%, 6.7% and 0.7% according to the maximum tolerated dose (24/26 mg, 49/51 mg and 97/103 mg, respectively; p=0.026). After treatment with sacubitril/valsartan, patients with at least one episode of AT/AF decreased from 32.6% to 26.5% (24/26 mg), 24.3% (49/51 mg) and 6.9% (97/103 mg); p=.041. A significant decrease in the number of PVC (-28 per hour) and in the rate of appropriate shock (-0.8% per year) were seen in patients with a previous diagnosis of paroxysmal or persistent AF. Patients with permanent AF (n=7) experienced no benefits from sacubitril/valsartan therapy in terms of arrhythmic burden reduction. Patients with a CRT device (41%) experienced a significant increase in biventricular pacing time (+3% per day). Discussion Therapy with sacubitril/valsartan could decrease arrhythmic burden in patients with non-permanent AF and HFrEF and reduce subclinical supraventricular arrhythmias in patients with no history of AF.

929 LEADLESS PACEMAKER IMPLANTATION FOLLOWING TRANSVENOUS LEAD EXTRACTION: DATA FROM HIGH-VOLUME REFERRAL CENTERS

Abstract Background limited data on real-world safety and efficacy of leadless pacemakers (LPMs) in patients who underwent transvenous lead extraction (TLE) are currently available. The present study aims to assess long-term safety and efficacy of LPMs implantation following TLE, compared with LPM de novo implant patients. Methods consecutive patients who underwent LPM implantation in 12 centers joining the International LEAdless PacemakEr (i-LEAPER) registry were enrolled end retrospectively considered. Patients receiving LPM following TLE (n=184) were compared with patients with de novo implant (n=995). The primary endpoint was LPM-related complications rate at implant and during follow-up (FU). Additionally, differences in electrical performance were assessed between the two groups. Results 1179 patients were enrolled in this study and followed for a median of 33 months. LPM related major complications and all-cause mortality did not differ among the two groups (1.6% TLE group vs. 2.2% de novo group, p=0.785, and 5.4% TLE group vs. 7.8% de novo group, p=0.288, respectively). Pacing threshold (PT) resulted higher in the TLE group throughout the whole follow-up (FU) (Figure 1). Higher PTs were recorded in LPMs implanted at same location from where the previous transvenous lead was removed, as far as 24-months postimplant (Figure 2), with a higher proportion of patients with high PT (&amp;gt;1 to 2V @0.24ms) in the first group at implant, 1-month, and 12-month FU (Figure 3). Conclusion In this real-world registry, LPMs showed a satisfactory safety and efficacy profile after TLE. In the post-TLE cohort, better electrical parameters were obtained when LPMs were implanted at a different location from where the previous transvenous lead was extracted.

The Advanced-Stage Hodgkin Lymphoma International Prognostic Index: Development and Validation of a Clinical Prediction Model From the HoLISTIC Consortium.

The International Prognostic Score (IPS) has been used in classic Hodgkin lymphoma (cHL) for 25 years. However, analyses have documented suboptimal performance of the IPS among contemporarily treated patients. Harnessing multisource individual patient data from the Hodgkin Lymphoma International Study for Individual Care consortium, we developed and validated a modern clinical prediction model. Model development via Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines was performed on 4,022 patients with newly diagnosed advanced-stage adult cHL from eight international phase III clinical trials, conducted from 1996 to 2014. External validation was performed on 1,431 contemporaneously treated patients from four real-world cHL registries. To consider association over a full range of continuous variables, we evaluated piecewise linear splines for potential nonlinear relationships. Five-year progression-free survival (PFS) and overall survival (OS) were estimated using Cox proportional hazard models. The median age in the development cohort was 33 (18-65) years; nodular sclerosis was the most common histology. Kaplan-Meier estimators were 0.77 for 5-year PFS and 0.92 for 5-year OS. Significant predictor variables included age, sex, stage, bulk, absolute lymphocyte count, hemoglobin, and albumin, with slight variation for PFS versus OS. Moreover, age and absolute lymphocyte count yielded nonlinear relationships with outcomes. Optimism-corrected c-statistics in the development model for 5-year PFS and OS were 0.590 and 0.720, respectively. There was good discrimination and calibration in external validation and consistent performance in internal-external validation. Compared with the IPS, there was superior discrimination for OS and enhanced calibration for PFS and OS. We rigorously developed and externally validated a clinical prediction model in > 5,000 patients with advanced-stage cHL. Furthermore, we identified several novel nonlinear relationships and improved the prediction of patient outcomes. An online calculator was created for individualized point-of-care use.

Real-World Management of Pharmacological Thromboprophylactic Strategies for COVID-19 Patients in Japan

Data on prophylactic anticoagulation are important in understanding the current issues, unmet needs, and optimal management of Japanese COVID-19 patients. This study aimed to investigate the clinical management strategies for prophylactic anticoagulation of COVID-19 patients in Japan. The CLOT-COVID study was a multicenter observational study that enrolled 2,894 consecutive hospitalized patients with COVID-19. The study population consisted of 2,889 patients (after excluding 5 patients with missing data); it was divided into 2 groups: patients with pharmacological thromboprophylaxis (n=1,240) and those without (n=1,649). Furthermore, we evaluated the 1,233 patients who received prophylactic anticoagulation-excluding 7 patients who could not be classified based on the intensity of their anticoagulants-who were then divided into 2 groups: patients receiving prophylactic anticoagulant doses (n=889) and therapeutic anticoagulant doses (n=344). The most common pharmacological thromboprophylaxis anticoagulant was unfractionated heparin (68.2%). The severity of COVID-19 at admission was a predictor of the implementation of pharmacological thromboprophylaxis in the multivariable analysis (moderate vs mild: OR: 16.6; 95% CI:13.2-21.0; P< 0.001, severe vs mild: OR: 342.6, 95%CI: 107.7-1090.2; P< 0.001). It was also a predictor of the usage of anticoagulants of therapeutic doses in the multivariable analysis (moderate vs mild: OR: 2.10; 95%CI: 1.46-3.02; P< 0.001, severe vs mild: OR: 5.96; 95%CI: 3.91-9.09; P<0.001). In the current real-world Japanese registry, pharmacological thromboprophylaxis, especially anticoagulants at therapeutic doses, was selectively implemented in COVID-19 patients with comorbidities and severe COVID-19 status at admission.

Efficacy and Safety of Clopidogrel Versus Ticagrelor for Stabilized Patients With Acute Coronary Syndromes After Percutaneous Coronary Intervention: Results From a Real-World Registry in China.

The first 3 months after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) is a high-risk period for adverse events, including ischemic and bleeding events, which decrease greatly with time. It is worth investigating whether the use of potent P2Y12 inhibitors is necessary after the early stage. The purpose of this study was to investigate the differences in clinical outcomes between clopidogrel and ticagrelor in stable patients without ischemic or major bleeding events during the first 3 months after PCI. Data for this study were obtained from the PHARM-ACS registry (NCT04184583). Patients who were free from ischemic and major bleeding events in the first 3 months after PCI were enrolled. Inverse probability of treatment weighting (IPTW) and Cox proportional hazards model were applied to compare the differences in clinical outcomes between the 2 groups. Major adverse cardiovascular and cerebrovascular events (MACCE) were considered the primary end point, and major bleeding was considered the secondary end point. A total of 6662 patients were included in this study. Of these, 3465 were treated with clopidogrel plus aspirin (clopidogrel group) and 3197 with ticagrelor plus aspirin (ticagrelor group). There were no significant differences in MACCE after IPTW adjustment for baseline variables (IPTW-adjusted HR, 1.06; 95% CI, 0.90-1.25) or major bleeding events (IPTW-adjusted HR, 0.97; 95% CI, 0.67-1.41) between the 2 groups. However, the incidence of minor bleeding in the clopidogrel group was significantly lower than that in the ticagrelor group (IPTW-adjusted HR, 0.65; 95% CI, 0.59-0.71). In patients with ACS who were free from ischemic or major bleeding events during the first 3 months after PCI, the subsequent clopidogrel treatment might reduce minor bleeding events without increasing the risk of MACCE compared with ticagrelor. However, the results still need to be confirmed by large randomized controlled studies in the future.

Admission lactate level and the GRACE 2.0 score are independent and additive predictors of 30-day mortality of STEMI patients treated with primary PCI-Results of a real-world registry.

In many of the risk estimation algorithms for patients with ST-elevation myocardial infarction (STEMI), heart rate and systolic blood pressure are key predictors. Yet, these parameters may also be altered by the applied medical treatment / circulatory support without concomitant improvement in microcirculation. Therefore, we aimed to investigate whether venous lactate level, a well-known marker of microcirculatory failure, may have an added prognostic value on top of the conventional variables of the "Global Registry of Acute Coronary Events" (GRACE) 2.0 model for predicting 30-day all-cause mortality of STEMI patients treated with primary percutaneous coronary intervention (PCI). In a prospective single-center registry study conducted from May 2020 through April 2021, we analyzed data of 323 cases. Venous blood gas analysis was performed in all patients at admission. Nested logistic regression models were built using the GRACE 2.0 score alone (base model) and with the addition of venous lactate level (expanded model) with 30-day all-cause mortality as primary outcome measure. Difference in model performance was analyzed by the likelihood ratio (LR) test and the integrated discrimination improvement (IDI). Independence of the predictors was evaluated by the variance inflation factor (VIF). Discrimination and calibration was characterized by the c-statistic and calibration intercept / slope, respectively. Addition of lactate level to the GRACE 2.0 score improved the predictions of 30-day mortality significantly as assessed by both LR test (LR Chi-square = 8.7967, p = 0.0030) and IDI (IDI = 0.0685, p = 0.0402), suggesting that the expanded model may have better predictive ability than the GRACE 2.0 score. Furthermore, the VIF was 1.1203, indicating that the measured lactate values were independent of the calculated GRACE 2.0 scores. Our results suggest that admission venous lactate level and the GRACE 2.0 score may be independent and additive predictors of 30-day all-cause mortality of STEMI patients treated with primary PCI.