Independent Clinical Events Committee Research Articles

Three-year outcomes for transcatheter repair in patients with mitral regurgitation from the CLASP study.

Mitral valve transcatheter edge-to-edge repair (M-TEER) is an effective option for treatment of mitral regurgitation (MR). We previously reported favorable 2-year outcomes for the PASCAL transcatheter valve repair system. We report 3-year outcomes from the multinational, prospective, single-arm CLASP study with analysis by functional MR(FMR) and degenerative MR (DMR). Patients with core-lab determined MR ≥ 3+ were deemed candidates for M-TEER by the local heart team. Major adverse events were assessed by an independent clinical events committee to 1 year and by sites thereafter. Echocardiographic outcomes were evaluated by the core laboratory to 3 years. The study enrolled 124 patients, 69% FMR; 31% DMR (60% NYHA class III-IVa, 100% MR ≥ 3+). The 3-year Kaplan-Meier estimate for survival was 75% (66% FMR; 92% DMR) and freedom from heart failure hospitalization (HFH) was 73% (64% FMR; 91% DMR), with 85% reduction in annualized HFH rate (81% FMR; 96% DMR) (p < 0.001). MR ≤ 2+ was achieved and maintained in 93% of patients (93% FMR; 94% DMR) and MR ≤ 1+ in 70% of patients (71% FMR; 67% DMR) (p < 0.001). The mean left ventricular end-diastolic volume (181 mL at baseline) decreased progressively by 28 mL [p < 0.001]. NYHA class I/II was achieved in 89% of patients (p < 0.001). The 3-year results from the CLASP study demonstrated favorable and durable outcomes with the PASCAL transcatheter valve repair system in patients with clinically significant MR. These results add to the growing body of evidence establishing the PASCAL system as a valuable therapy for patients with significant symptomatic MR.

PD15-11 EFFICACY AND SAFETY OF BIODEGRADABLE RECTAL SPACER BALLOON IN PATIENTS RECEIVING PROSTATE IMRT: AN INTERNATIONAL PHASE 3 RANDOMIZED TRIAL

You have accessJournal of UrologyCME1 Apr 2023PD15-11 EFFICACY AND SAFETY OF BIODEGRADABLE RECTAL SPACER BALLOON IN PATIENTS RECEIVING PROSTATE IMRT: AN INTERNATIONAL PHASE 3 RANDOMIZED TRIAL Daniel Song, Mateusz Dabkowski, Warsaw Poland, Paulo Costa, Rizwan Nurani, Michael Kos, Ben Vanneste, David Margel, Eli Sapir, Shawn Zimberg, Oleksandr Boychak, Edward Soffen, Abdulla Alhasso, Kenneth Tokita, Dian Wang, Zvi Symon, and Richard Hudes Daniel SongDaniel Song More articles by this author , Mateusz DabkowskiMateusz Dabkowski More articles by this author , Warsaw PolandWarsaw Poland More articles by this author , Paulo CostaPaulo Costa More articles by this author , Rizwan NuraniRizwan Nurani More articles by this author , Michael KosMichael Kos More articles by this author , Ben VannesteBen Vanneste More articles by this author , David MargelDavid Margel More articles by this author , Eli SapirEli Sapir More articles by this author , Shawn ZimbergShawn Zimberg More articles by this author , Oleksandr BoychakOleksandr Boychak More articles by this author , Edward SoffenEdward Soffen More articles by this author , Abdulla AlhassoAbdulla Alhasso More articles by this author , Kenneth TokitaKenneth Tokita More articles by this author , Dian WangDian Wang More articles by this author , Zvi SymonZvi Symon More articles by this author , and Richard HudesRichard Hudes More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003262.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Rectal gel spacers have been shown to reduce rectal side effects in patients receiving prostate radiation. However, concerns remain regarding precise and reproducible gel injection. We report on a novel rectoprostatic spacer balloon which allows potential for controlled, adaptable deployment without time constraints associated with hydrogel injection. To determine efficacy and safety, the study had co-primary hypotheses: 1) Balloon spacer would result in ≥25% reduction of rectal V70 in >75% of subjects, and 2) Implantation procedure-related and rectal ≥ Grade 1 adverse events would be non-inferior in balloon vs control subjects (events with duration ≥2 days within 6 months, CTCAE 4.0). METHODS: 222 subjects were enrolled at 16 centers. All patients had biopsy-proven T1-T3 prostate cancer without MRI evidence of posterior extraprostatic invasion. Patients receiving brachytherapy or whole pelvic RT were excluded. Randomization was 2:1 (balloon:control) and subject-blinded. All patients underwent transperineal TRUS-guided fiducial marker placement±biodegradable balloon, followed by IMRT. For efficacy endpoint comparisons, plans were generated by central core lab on pre- and post-implant CT scans (81 Gy in 1.8 Gy fractions). Adverse events were reviewed by blinded, independent Clinical Events Committee. RESULTS: The primary efficacy endpoint was met, with 97.9% of balloon subjects (139/142) having rectal V70 reduction of >25% (pre- vs post-implant; p<0.001, 95% CI (94.0, 99.6%). Mean V70 was 7.0 % pre- vs 1.1% post-implant. Similar decreases were observed in rectal V40–V80. Mean prostate-rectal spacing achieved (19+3.7mm) was maintained through radiation treatment (18+3.9mm). Balloon placement was successful in 99% of subjects. The primary safety endpoint was met with balloon subjects experiencing fewer ≥ Grade 1 events, 18% vs 23% (p<0.001, 95% CI -15.7%, 5.5%). Event rate was higher in balloon subjects in early post-implant period, but control arm surpassed balloon group at/beyond day 44 post-implant. On pre-defined secondary endpoint of ≥Grade 2 events, rates were lower in balloon subjects (4.3% vs 6.5%). Complete balloon resorption was observed on 6-month CT in 98.5% (133/135) of subjects. CONCLUSIONS: Biodegradable rectal spacer balloon was effective in significantly reducing dose to rectum, and associated with decreased cumulative rectal plus implantation-related adverse events. Balloon resorption was consistently observed by 6 months. Source of Funding: BioProtect, Ltd © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e423 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniel Song More articles by this author Mateusz Dabkowski More articles by this author Warsaw Poland More articles by this author Paulo Costa More articles by this author Rizwan Nurani More articles by this author Michael Kos More articles by this author Ben Vanneste More articles by this author David Margel More articles by this author Eli Sapir More articles by this author Shawn Zimberg More articles by this author Oleksandr Boychak More articles by this author Edward Soffen More articles by this author Abdulla Alhasso More articles by this author Kenneth Tokita More articles by this author Dian Wang More articles by this author Zvi Symon More articles by this author Richard Hudes More articles by this author Expand All Advertisement PDF downloadLoading ...

Identification of vulnerable non-culprit lesions by coronary computed tomography angiography in patients with chronic coronary syndrome and diabetes mellitus.

Among patients with diabetes mellitus (DM) and chronic coronary syndrome (CCS), non-culprit lesions (NCLs) are responsible for a substantial number of future major adverse cardiovascular events (MACEs). Thus, we aimed to establish the natural history relationship between adverse plaque characteristics (APCs) of NCLs non-invasively identified by coronary computed tomography angiography (CCTA) and subsequent MACEs in these patients. Between January 2016 and January 2019, 523 patients with DM and CCS were included in the present study after CCTA and successful percutaneous coronary intervention (PCI). All patients were followed up for MACEs (the composite of cardiac death, myocardial infarction, and unplanned coronary revascularization) until January 2022, and the independent clinical event committee classified MACEs as indeterminate, culprit lesion (CL), and NCL-related. The primary outcome was MACEs arising from untreated NCLs during the follow-up. The association between plaque characteristics detected by CCTA and primary outcomes was determined by Marginal Cox proportional hazard regression. Overall, 1,248 NCLs of the 523 patients were analyzed and followed up for a median of 47 months. The cumulative rates of indeterminate, CL, and NCL-related MACEs were 2.3%, 14.5%, and 20.5%, respectively. On multivariate analysis, NCLs associated with recurrent MACEs were more likely to be characterized by a plaque burden >70% [hazard ratio (HR), 4.35, 95% confidence interval (CI): 2.92-6.44], a low-density non-calcified plaque (LDNCP) volume >30 mm3 (HR: 3.40, 95% CI: 2.07-5.56), a minimal luminal area (MLA) <4 mm2 (HR: 2.30, 95% CI: 1.57-3.36), or a combination of three APCs (HR: 13.69, 95% CI: 9.34-20.12, p < 0.0001) than those not associated with recurrent MACEs. Sensitivity analysis regarding all indeterminate MACEs as NCL-related ones demonstrated similar results. In DM patients who presented with CCS and underwent PCI, half of the MACEs occurring during the follow-up were attributable to recurrence at the site of NCLs. NCLs responsible for unanticipated MACEs were frequently characterized by a large plaque burden and LDNCP volume, a small MLA, or a combination of these APCs, as determined by CCTA.

Complementary evidence on the performance of coronary stents generated by a randomized controlled trial and a worldwide registry

Large-scale registries can provide valuable complementary data to randomized controlled trials (RCT) for the postmarketing evaluation of coronary stents, but their scientific relevance remains debated. We sought to compare the evidence on the performance of a single coronary stent platform generated by the RCT for its regulatory approval and a well-conducted international registry. Patients treated with the Ultimaster coronary stent in the CENTURY II (CII-UM) trial (n=551) were compared to patients in the real-world e-ULTIMASTER (e-UM) registry (n=35,389). All major events were adjudicated by an independent clinical event committee in both studies. Propensity weighted analysis was used to balance baseline and procedural differences between the 2 populations. Coronary artery disease was more complex in e-UM compared to CII-UM, including more acute coronary syndromes, multivessel disease, left main, arterial, or venous grafts, and chronic total occlusions (P < .005 for all). At one-year follow-up and after excluding periprocedural myocardial infarction (MI) there was no statistically significant difference between CII-UM and e-UMregarding all-cause death (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.26-1.20, P=.14), cardiac death (HR 0.71, 95% CI 0.29-1.72, P=.45), target lesion failure (HR 1.18, 95% CI 0.78-1.78, P=.44), and target vessel MI (HR 0.76, 95% CI 0.24-2.38, P=.63). However, target vessel revascularization rate was significantly higher in CII-UM than in e-UM, HR 1.78, 95% CI 1.23-2.56, P=.002. A well-conducted large-scale registry can provide valuable complementary evidence to RCTs on the postmarket performance of new coronary stents, across a wider range of uses and various geographic areas.

Thirty-day and one-year outcomes of the Navitor transcatheter heart valve in patients with aortic stenosis: the prospective, multicentre, global PORTICO NG Study.

The Navitor transcatheter heart valve (THV) is a self-expanding valve, with an intra-annular leaflet position and an outer cuff intended to reduce paravalvular leak (PVL). The aim of the PORTICO NG Study is to assess the safety and performance of the Navitor THV in patients with symptomatic, severe aortic stenosis who are at high or extreme surgical risk. PORTICO NG is a prospective, multicentre, global, single-arm, investigational study with follow-up at 30 days, 1 year, and annually up to 5 years. The primary endpoints are all-cause mortality and moderate or greater PVL at 30 days. Valve Academic Research Consortium-2 events and valve performance are assessed by an independent clinical events committee and echocardiographic core laboratory. A total of 120 high- or extreme-risk subjects (age 83.5±5.4 years; 58.3% female; Society of Thoracic Surgeons score 4.0±2.0%) were enrolled in the European conformity (CE) mark cohort. Procedural success was high at 97.5%. At 30 days, the rate of all-cause mortality was 0%, and no subjects had moderate or greater PVL. The rate of disabling stroke was 0.8%, life-threatening bleeding was 2.5%, stage 3 acute kidney injury 0%, major vascular complications 0.8%, and new pacemaker implantation 15.0%. At 1 year, the rates of all-cause mortality and disabling stroke were 4.2% and 0.8%, respectively. The rate of moderate PVL was 1.0% at 1 year. Haemodynamic performance with a mean gradient of 7.5±3.2 mmHg and effective orifice area of 1.9±0.4 cm2 was sustained up to 1 year. The PORTICO NG Study demonstrates low rates of adverse events and PVL up to 1 year in patients at high or extreme surgical risk, confirming the safety and efficacy of the Navitor THV system.

Virtual Care Team Guided Management of Patients With Heart Failure During Hospitalization

BackgroundScalable and safe approaches for heart failure guideline-directed medical therapy (GDMT) optimization are needed. ObjectivesThe authors assessed the safety and effectiveness of a virtual care team guided strategy on GDMT optimization in hospitalized patients with heart failure with reduced ejection fraction (HFrEF). MethodsIn a multicenter implementation trial, we allocated 252 hospital encounters in patients with left ventricular ejection fraction ≤40% to a virtual care team guided strategy (107 encounters among 83 patients) or usual care (145 encounters among 115 patients) across 3 centers in an integrated health system. In the virtual care team group, clinicians received up to 1 daily GDMT optimization suggestion from a physician-pharmacist team. The primary effectiveness outcome was in-hospital change in GDMT optimization score (+2 initiations, +1 dose up-titrations, −1 dose down-titrations, −2 discontinuations summed across classes). In-hospital safety outcomes were adjudicated by an independent clinical events committee. ResultsAmong 252 encounters, the mean age was 69 ± 14 years, 85 (34%) were women, 35 (14%) were Black, and 43 (17%) were Hispanic. The virtual care team strategy significantly improved GDMT optimization scores vs usual care (adjusted difference: +1.2; 95% CI: 0.7-1.8; P < 0.001). New initiations (44% vs 23%; absolute difference: +21%; P = 0.001) and net intensifications (44% vs 24%; absolute difference: +20%; P = 0.002) during hospitalization were higher in the virtual care team group, translating to a number needed to intervene of 5 encounters. Overall, 23 (21%) in the virtual care team group and 40 (28%) in usual care experienced 1 or more adverse events (P = 0.30). Acute kidney injury, bradycardia, hypotension, hyperkalemia, and hospital length of stay were similar between groups. ConclusionsAmong patients hospitalized with HFrEF, a virtual care team guided strategy for GDMT optimization was safe and improved GDMT across multiple hospitals in an integrated health system. Virtual teams represent a centralized and scalable approach to optimize GDMT.

Abstract Number ‐ 33: Patients Treated with The Pipeline Shield Flow Diverter Enrolled Within the INSPIRE Study: Primary analysis

Introduction The INSPIRE study collects post‐market data on multiple devices from more than 40 centers world‐wide. One of these devices is the PipelineTM Flex flow diverter with Shield TechnologyTM (Pipeline Shield) for the treatment of intracranial aneurysms. The Shield surface modification is designed to enhance endothelization of the device with low thromboembolic risks. We analyze the efficacy and safety outcomes after Pipeline Shield therapy at the 1‐year follow‐up in a large prospective study. Methods INSPIRE is a prospective, multicenter, single arm study. Patients are followed for 1‐year post‐procedure and results are adjudicated by an independent Clinical Events Committee and Imaging Core Laboratory. All patients were treated per their hospital’s standard of care. The primary safety endpoint was neurological death or major stroke in the treated vascular area. The primary efficacy endpoint was complete aneurysm occlusion without significant parent artery stenosis (&gt;50%) or retreatment. For this analysis, the last‐available observation was carried forward to overcome differences between centers’ imaging schedules. Results A total of 537 patients were enrolled, with 504 patients with 488 aneurysms included in the analysis (mean age 53.8±12.2, 77.0% [388/504] female). The majority of aneurysms were located in the ICA (74.2%, 362/488). Of the remaining aneurysms, 16.0% (78/488) were in the anterior circulation and 9.8% (48/488) were in the posterior circulation. The majority of aneurysms were saccular (89.3% [436/488]). A total of 47.1% of aneurysms were small (&lt; 7mm, 230/488), 30.9% were medium (7‐&lt; 13 mm, 151/488), 16.8% were large (13‐&lt; 25 mm, 82/488), and 5.1% were giant (&gt; = 25 mm, 25/488). Adjunctive devices were used in 20.9% (102/488) of cases, including balloon (42.2% [19/43]), coil (63.7%, [65/102]), stent (5.9% [6/102]), or flow diverter (9.8% [10/102]). At 1‐year post‐procedure, complete occlusion (Raymond Roy Class I) was achieved in 74.9% (326/435) aneurysms. The primary safety endpoint occurred in 2.2% (11/504) patients. The primary endpoint was achieved in 73.2% (290/396) cases; reasons for primary endpoint failure included residual neck (5.8% [23/396]), residual aneurysm (19.4% [77/396]), stenosis &gt;50% (1.0% [4/396]), and re‐treatment (1.5% [6/396]). Among ICA aneurysms, complete occlusion was achieved in 78.1% (249/319). The primary safety endpoint occurred in 2.0% (7/356) patients. The primary endpoint was achieved in 77.1% (225/292) cases; reasons for primary endpoint failure among ICA aneurysms included residual neck (5.5% [16/292]), residual aneurysm (16.4% [48/292]), stenosis &gt;50% (0.7% [2/292]), and re‐treatment (1.4% [67/292]). Conclusions INSPIRE data suggests good rates of complete occlusion, efficacy, and safety among a large cohort of patients with aneurysms in a variety of challenging locations and sizes treated with the Pipeline Shield device, with adjudication by CEC and Imaging Core Lab ensuring high quality of these data.

30-Day Clinical Outcomes of a Self-Expanding Transcatheter Aortic Valve: The International PORTICO NG Study

BackgroundThe self-expanding, intra-annular Navitor (Abbott Structural Heart) valve includes an outer cuff to reduce paravalvular leak (PVL) and large stent cells for future coronary access. ObjectivesThe purpose of the PORTICO NG (Evaluation of the Portico NG [Next Generation] Transcatheter Aortic Valve in High and Extreme Risk Patients With Symptomatic Severe Aortic Stenosis) study is to evaluate the safety and effectiveness of the Navitor valve in patients with symptomatic, severe aortic stenosis who are at high or extreme surgical risk. MethodsPORTICO NG is a prospective, multicenter, global study with follow-up at 30 days, 1 year, and annually through 5 years. The primary endpoints are all-cause mortality and moderate or greater PVL at 30 days. Valve Academic Research Consortium-2 events and valve performance are assessed by an independent clinical events committee and echocardiographic core laboratory. ResultsA total of 260 subjects were treated at 26 clinical sites across Europe, Australia, and the United States between September 2019 and August 2022. The mean age was 83.4 ± 5.4 years, 57.3% were female, and the average Society of Thoracic Surgeons score was 3.9% ± 2.1%. At 30 days, the rate of all-cause mortality was 1.9%, and no subjects had moderate or greater PVL. The rate of disabling stroke was 1.9%, life-threatening bleeding was 3.8%, stage 3 acute kidney injury was 0.8%, major vascular complications were 4.2%, and new permanent pacemaker implantation was 19.0%. Hemodynamic performance included a mean gradient of 7.4 ± 3.5 mm Hg and an effective orifice area of 2.00 ± 0.47 cm2. ConclusionsThe Navitor valve is safe and effective for the treatment of subjects with severe aortic stenosis who are at high or greater risk for surgery, which is supported by low rates of adverse events and PVL. (Evaluation of the Portico NG [Next Generation] Transcatheter Aortic Valve in High and Extreme Risk Patients With Symptomatic Severe Aortic Stenosis [PORTICO NG]; NCT04011722)

Two‐Year Outcomes With a Next‐Generation Left Atrial Appendage Device: Final Results of the PINNACLE FLX Trial

Background The PINNACLE FLX (Protection Against Embolism for Non-valvular AF [Atrial Fibrillation] Patients: Investigational Device Evaluation of the Watchman FLX LAA [Left Atrial Appendage] Closure Technology) trial evaluated the safety and efficacy of a next-generation left atrial appendage closure device (WATCHMAN FLX; Boston Scientific, Marlborough, MA). At 1 year, the study met the primary end points of safety and anatomical efficacy/appendage closure. This final report of the PINNACLE FLX trial includes the prespecified secondary end point of ischemic stroke or systemic embolism at 2 years, also making it the first report of 2-year outcomes with this next-generation left atrial appendage closure device. Methods and Results Patients with nonvalvular atrial fibrillation with CHA2DS2-VASc score ≥2 (men) or ≥3 (women), with an appropriate rationale for left atrial appendage closure, were enrolled to receive the left atrial appendage closure device at 29 US centers. Adverse events were assessed by an independent clinical events committee, and imaging was assessed by independent core laboratories. Among 395 implanted patients (36% women; mean age, 74 years; CHA2DS2-VASc, 4.2±1.5), the secondary efficacy end point of 2-year ischemic stroke or systemic embolism was met, with an absolute rate of 3.4% (annualized rate, 1.7%) and an upper 1-sided 95% confidence bound of 5.3%, which was superior to the 8.7% performance goal. Two-year rates of adverse events were as follows: 9.3% all-cause mortality, 5.5% cardiovascular death, 3.4% all stroke, and 10.1% major bleeding (Bleeding Academic Research Consortium 3 or 5). There were no additional systemic embolisms, device embolizations, pericardial effusions, or symptomatic device-related thrombi after 1 year. Conclusions The secondary end point of 2-year stroke or systemic embolism was met at 3.4%. In these final results of the PINNACLE FLX trial, the next-generation WATCHMAN FLX device demonstrated favorable safety and efficacy outcomes.

Propensity-Matched Outcomes Comparing TAVR in Bicuspid vs Surgery in Tricuspid Aortic Valve Stenosis.

To compare 1-year outcomes in patients at low surgical risk with bicuspid aortic valve stenosis (AS) following transcatheter aortic valve replacement (TAVR) and low-risk patients with tricuspid AS following surgical aortic valve replacement (SAVR). The pivotal randomized, prospective, multicenter TAVR trials compared TAVR vs SAVR in patients with tricuspid AS. No such trials exist for bicuspid AS. The Low Risk Bicuspid Study is a prospective, single-arm, TAVR trial that enrolled 150 patients from 25 sites in the United States. A screening committee confirmed bicuspid anatomy and valve classification based on computed tomography using the Sievers classification. Annular measurements guided valve sizing. These patients were propensity-matched to the SAVR patients in the randomized Evolut Low Risk Trial using 1:1 5-to-1-digit Greedy method, resulting in 144 matched pairs. For both trials, an independent clinical events committee adjudicated all serious adverse events, and the same independent core laboratory assessed all echocardiograms. The 1-year composite of death, disabling stroke, or aortic valve-related rehospitalization for bicuspid TAVR vs tricuspid SAVR was 6 (4.2%) vs 6 (4.2%) (P = .99). The effective orifice area (2.2 ± 0.7 cm2 vs 2.0 ± 0.6 cm2) was larger and the valve gradient was lower (8.7 ± 3.9 mm Hg vs 11.2 ± 4.7 mm Hg) in the TAVR group at 1 year (both P < .001). Moderate/severe aortic regurgitation was present in 1 TAVR and 2 SAVR patients (0.8% vs 1.6%; P > .99). In this select group of low-risk bicuspid patients, in the short-term follow-up, TAVR appears to have similar outcomes to those seen in comparable low-risk tricuspid patients undergoing SAVR.

One-year cardiovascular outcomes after coronavirus disease 2019: The cardiovascular COVID-19 registry.

The long-term cardiovascular (CV) outcomes of COVID-19 have not been fully explored. This was an international, multicenter, retrospective cohort study conducted between February and December 2020. Consecutive patients ≥18 years who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 were included. Patients were classified into two cohorts depending on the nasopharyngeal swab result and clinical status: confirmed COVID-19 (positive RT-PCR) and control (without suggestive symptoms and negative RT-PCR). Data were obtained from electronic records, and clinical follow-up was performed at 1-year. The primary outcome was CV death at 1-year. Secondary outcomes included arterial thrombotic events (ATE), venous thromboembolism (VTE), and serious cardiac arrhythmias. An independent clinical event committee adjudicated events. A Cox proportional hazards model adjusted for all baseline characteristics was used for comparing outcomes between groups. A prespecified landmark analysis was performed to assess events during the post-acute phase (31-365 days). A total of 4,427 patients were included: 3,578 (80.8%) in the COVID-19 and 849 (19.2%) control cohorts. At one year, there were no significant differences in the primary endpoint of CV death between the COVID-19 and control cohorts (1.4% vs. 0.8%; HRadj 1.28 [0.56-2.91]; p = 0.555), but there was a higher risk of all-cause death (17.8% vs. 4.0%; HRadj 2.82 [1.99-4.0]; p = 0.001). COVID-19 cohort had higher rates of ATE (2.5% vs. 0.8%, HRadj 2.26 [1.02-4.99]; p = 0.044), VTE (3.7% vs. 0.4%, HRadj 9.33 [2.93-29.70]; p = 0.001), and serious cardiac arrhythmias (2.5% vs. 0.6%, HRadj 3.37 [1.35-8.46]; p = 0.010). During the post-acute phase, there were no significant differences in CV death (0.6% vs. 0.7%; HRadj 0.67 [0.25-1.80]; p = 0.425), but there was a higher risk of deep vein thrombosis (0.6% vs. 0.0%; p = 0.028). Re-hospitalization rate was lower in the COVID-19 cohort compared to the control cohort (13.9% vs. 20.6%; p = 0.001). At 1-year, patients with COVID-19 experienced an increased risk of all-cause death and adverse CV events, including ATE, VTE, and serious cardiac arrhythmias, but not CV death. URL: https://www.clinicaltrials.gov. Unique identifier: NCT04359927.

Paclitaxel-coated balloons for femoropopliteal peripheral arterial disease: final five-year results of the IN.PACT Global Study.

Numerous randomised controlled trials (RCTs) have demonstrated the superiority of paclitaxel drug-coated balloons (DCBs) over non-coated angioplasty balloons for treatment of femoropopliteal peripheral arterial disease (PAD). There is a paucity of clinical evidence in more complex patients who are often excluded from RCTs and long-term data up to 5 years are very limited in PAD revascularisation studies. This is a report of the 5-year outcomes from the prospective, single-arm, international IN.PACT Global Study. The IN.PACT Admiral DCB was evaluated for femoropopliteal atherosclerotic disease treatment in a real-world patient population. In total, 1,535 patients were enrolled at 64 international sites. The prespecified clinical cohort included 1,406 patients with claudication or rest pain. Patients were evaluated up to 5 years for the occurrence of adverse events and clinically driven target lesion revascularisations (CD-TLR). The mean lesion length was 12.1±9.5 cm in 1,774 lesions, 18.0% had in-stent restenosis, 35.5% were total occlusions and 68.7% were calcified. Per independent clinical events committee adjudication, the Kaplan-Meier estimate of freedom from CD-TLR up to 5 years was 69.4%, and the restricted mean survival time to first CD-TLR was 1,470.1 days. Outcomes were similar for males and females; freedom from CD-TLR was 69.1% in females and 69.6% in males (p=0.602). The cumulative incidence of major adverse events for the clinical cohort was 45.9% and freedom from all-cause mortality with the vital status update was 78.9% up to 5 years. The IN.PACT Admiral DCB demonstrated safe and durable outcomes in real-world participants with complex femoropopliteal disease. gov: NCT01609296.

Spontaneous coronary artery dissection and ST-segment elevation myocardial infarction: Does clinical presentation matter?

BackgroundSome patients with spontaneous coronary artery dissection (SCAD) present as ST-segment-elevation myocardial infarction (STEMI). This study evaluates the characteristics, management and outcomes of SCAD patients presenting as STEMI compared to non-ST-segment elevation myocardial infarction (NSTEMI). MethodsWe analysed data from consecutive patients included in the prospective Spanish Registry on SCAD. All coronary angiograms were centrally reviewed. All adverse events were adjudicated by an independent Clinical Events Committee. ResultsBetween June 2015 to December 2020, 389 patients were included. Forty-two percent presented with STEMI and 56% with NSTEMI. STEMI patients showed a worse distal flow (TIMI flow 0–1 38% vs 19%, p < 0.001) and more severe (% diameter stenosis 85 ± 18 vs 75 ± 21, p < 0.001) and longer (42 ± 23 mm vs 35 ± 24 mm, p = 0.006) lesions. Patients with STEMI were more frequently treated with percutaneous coronary intervention (PCI) (31% vs 16%, p < 0.001) and developed more frequently left ventricular systolic dysfunction (21% vs 8%, p < 0.001). No differences were found in combined major adverse events during admission (7% vs 5%, p = 0.463), but in-hospital reinfarctions (5% vs 1.4%, p = 0.039) and cardiogenic shock (2.6% vs 0%, p = 0.019) were more frequently seen in the STEMI group. At late follow-up (median 29 months) no differences were found in the incidence of major adverse cardiac and cerebrovascular events (13% vs 13%, p-value = 0.882) between groups. ConclusionsPatients with SCAD and STEMI had a worse angiographic profile and were more frequently referred to PCI compared to NSTEMI patients. Despite these disparities, both short and long-term prognosis were similar in STEMI and NSTEMI SCAD patients.

Indobufen or Aspirin on Top of Clopidogrel After Coronary Drug-Eluting Stent Implantation (OPTION): A Randomized, Open-Label, End Point-Blinded, Noninferiority Trial.

Dual antiplatelet therapy (DAPT) with aspirin as a background therapy has become the standard care after percutaneous coronary intervention. However, some adverse noncardiac effects limited the use of aspirin in clinical practice. Thus, evaluation of pharmacological alternatives to aspirin is attractive. Previous data indicated that indobufen could lessen the unwanted side effects of aspirin while retaining the antithrombotic efficacy, but its combination with a P2Y12 inhibitor still lacks randomized clinical trial evidence. In this randomized, open-label, noninferiority trial, patients with negative cardiac troponin undergoing coronary drug-eluting stent implantation were randomly assigned in a 1:1 ratio to receive either indobufen-based DAPT (indobufen 100 mg twice a day plus clopidogrel 75 mg/d for 12 months) or conventional DAPT (aspirin 100 mg/d plus clopidogrel 75 mg/d for 12 months). The primary end point was a 1-year composite of cardiovascular death, nonfatal myocardial infarction, ischemic stroke, definite or probable stent thrombosis, or Bleeding Academic Research Consortium criteria type 2, 3, or 5 bleeding. The end points were adjudicated by an independent Clinical Event Committee. Between January 11, 2018, and October 12, 2020, 4551 patients were randomized in 103 cardiovascular centers: 2258 patients to the indobufen-based DAPT group and 2293 to the conventional DAPT group. The primary end point occurred in 101 patients (4.47%) in the indobufen-based DAPT group and 140 patients (6.11%) in the conventional DAPT group (absolute difference, -1.63%; Pnoninferiority<0.001; hazard ratio, 0.73 [95% CI, 0.56-0.94]; P=0.015). Cardiovascular death, nonfatal myocardial infarction, ischemic stroke, and stent thrombosis were observed in 0.13%, 0.40%, 0.80%, and 0.22% of patients in the indobufen-based DAPT group and 0.17%, 0.44%, 0.83%, and 0.17% of patients in the conventional DAPT group (all P>0.05). The occurrence of Bleeding Academic Research Consortium criteria type 2, 3, or 5 bleeding events was lower in the indobufen-based DAPT group compared with the conventional DAPT group (2.97% versus 4.71%; hazard ratio, 0.63 [95% CI, 0.46-0.85]; P=0.002), with the main decrease in type 2 bleeding (1.68% versus 3.49%; hazard ratio, 0.48 [95% CI, 0.33-0.70]; P<0.001). In Chinese patients with negative cardiac troponin undergoing drug-eluting stent implantation, indobufen plus clopidogrel DAPT compared with aspirin plus clopidogrel DAPT significantly reduced the risk of 1-year net clinical outcomes, which was driven mainly by a reduction in bleeding events without an increase in ischemic events. URL: https://www.chictr.org.cn; Unique identifier: ChiCTR-IIR-17013505.

Design and Rationale of Targeted Therapy With a Sirolimus-Eluting, Biodegradable Polymer Coronary Stent in Chronic Total Occlusions (TARGET CTO): A Multicenter, Open-Label, Randomized Noninferiority Trial.

Treatment of chronic total occlusions (CTOs) is referred to as the last frontier of percutaneous coronary interventions and is currently performed in 10% to 20% of procedures. Improved outcomes with newer generation drug-eluting stents require further research. The TARGET CTO trial (NCT03040934) is a prospective, multicenter, randomized, noninferiority trial that plans to randomize 196 subjects (1:1) to either a newer-generation sirolimus target-eluting stent or an everolimus-eluting stent. Patients are candidates if they present with at least 1 CTO lesion in a native coronary artery with a diameter of ≥2.50 mm to ≤4.00 mm and a length of <100 mm. In addition, 44 subjects will participate in an optical coherence tomography (OCT) substudy. Clinical follow-up is planned up to 5 years after stent implantation. Angiographic follow-up is planned at 12 months, whereas OCT will be obtained after the procedure, at 3 and 12 months. The primary end point is in-stent late lumen loss by quantitative coronary angiography at 12 months. The key secondary end point is neointimal thickness by OCT at 3 months. Imaging end points are assessed by an independent core lab. Clinical end points are adjudicated by an independent clinical events committee. The TARGET CTO trial compares a sirolimus target-eluting stent with an everolimus-eluting stent for management of CTOs according to contemporary interventional practices. The primary angiographic end points will be reported at 12 months and clinical follow-up will continue for up to 5 years.

Causes of death in patients with atrial fibrillation and a recent acute coronary syndrome or percutaneous coronary intervention: insights from the AUGUSTUS trial

Abstract Background Patients with atrial fibrillation (AF) and concomitant coronary artery disease are at increased risk for poor outcomes. Less is known about specific causes of death in this population. Methods We describe specific causes of death among patients with AF and acute coronary syndrome and/or percutaneous coronary intervention included in the AUGUSTUS trial and followed for 6 months. An independent clinical events committee, blinded to treatment assignment, adjudicated cause of death according to pre-defined criteria. The association between baseline factors and all-cause death was evaluated using Cox proportional hazards modeling. Results A total of 151 deaths occurred in 4614 patients and were adjudicated as follows: 111 (73.5%) deaths due to cardiovascular (CV) causes and 40 (26.5%) due to non-CV causes. The most common cause of CV death was sudden death (n=39 [35.1%]), followed by myocardial infarction (n=29 [26.1%]) and heart failure (n=24 [21.6%]). The most common causes of non-CV death were infection (n=11 [27.5%]), bleeding (n=8 [20.0%]), and malignancy (n=5 [12.5%]). Increasing age, African American race, history of heart failure, treatment with diuretics, and lower body weight were associated with an increased risk of all-cause death (Table). Conclusions Among patients with AF and coronary artery disease, cardiovascular causes were responsible for the majority of deaths within 6 months. Our findings provide relevant information to inform the design of future studies in this population. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): AUGUTUS was funded by Bristol Myers Squibb and Pfizer.

4 year outcomes in a prospective evaluation of transcatheter mitral valve-in-valve, valve-in-ring and valve-in-mitral annular calcification: results from the MITRAL trial

Abstract Background The MITRAL Trial (Mitral Implantation of TRAnscatheter vaLves) evaluates the safety and feasibility of balloon-expandable aortic transcatheter heart valves in patients with severe mitral valve disease with mitral annular calcification (MAC), failed surgical rings or failed bioprostheses. Purpose We sought to evaluate 4-year outcomes of patients enrolled in the MITRAL trial. Methods This is a prospective study that enrolled 91 high surgical risk patients at 13 sites in the U.S. 30 patients underwent Mitral Valve-in-Valve (MViV), 30 Valve-in-Ring (MViR) and 31 Valve-in-MAC (ViMAC). 4-year outcomes of these patients were evaluated in this analysis. Primary endpoints and key serious adverse events including deaths were adjudicated by an independent Clinical Events Committee. Cardiac computed tomography (CT) and echocardiographic images were evaluated by independent CT and Echocardiographic Core Laboratories. Results Mean age was 74.3±8.9 years. Most patients undergoing MViV and ViMAC were female (MVIV=63.3%, MViR=36.7% and ViMAC=71%). Mean STS score was 9.2±6.6% (MViV 10.2±6.5%, MViR 8.7±4.7%, ViMAC=8.6±8.2%). All-cause mortality at 4 years was higher for ViMAC and MViR: MViV=6.9% (cardiovascular 3.4%), MViR=48.1% (cardiovascular 18.5%), ViMAC=51.9% (cardiovascular 29.6%), p=0.002 (Figure 1). At 4 years, all survivors had ≤1+ mitral regurgitation and most had none or trace mitral regurgitation (MViV=87.5, MViR=33.3% and ViMAC=100%). Mean mitral valve gradients remained stable (MViV=5.9±2.2 mmHg, MViR= 6.6±5.1 mmHg, ViMAC=5.1±1.0 mmHg), Figure 2. Most survivors experienced significant improvement of symptoms and were in NYHA class I-II at 4-year follow-up (MViV=78.9%, MViR=66.7% and ViMAC=66.7%). Conclusions MViV is associated with excellent outcomes at 4 years. MViR and ViMAC were associated with higher mortality at 4 years. However, most survivors in all groups experienced sustained improvement of symptoms and stable THV performance at 4 years. Whether survival bias had an impact on THV performance and improved symptoms at follow-up is not known and deserves further evaluation. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Unrestricted Research Grant from Edwards Lifesciences.

Long-term effects of coronavirus disease 2019 on the cardiovascular system: the CV COVID-19 registry

Abstract Background Patients with COVID-19 have an increased risk of cardiovascular adverse events during the acute phase. However, the long-term cardiovascular outcomes are unknown. Objective We aimed to determine the long-term effects of COVID-19 in the cardiovascular system. Methods This is a multicenter, observational, retrospective registry conducted at 17 centers in Spain and Italy. Consecutive patients older than 18 years who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 in the participating institutions were included. Patients were classified into two groups, according to the results of the RT-PCR: COVID-19 positive or negative. The primary outcome was cardiovascular (CV) death at 1-year. The secondary outcomes included acute myocardial infarction, stroke, heart failure hospitalization, pulmonary embolism, and serious cardiac arrhythmias at 1-year. Outcomes were compared between the two groups. An independent clinical event committee adjudicated events. Results A total of 4427 patients were included, 3578 (80.8%) patients with COVID-19 and 849 (19.2%) without COVID-19. COVID-19 patients were older, had a higher rate of classical cardiovascular risk factors, except for active smoking, and had fewer comorbidities. At a median time of 13.5 (IQR 11.8–15.8) months, after an adjustment by baseline characteristics, there was no difference in CV death (1.4% vs. 1.1%; HR 1.03 [0.49–2.18]; p=0.941) between patients with COVID-19 and without. However, COVID-19 patients experienced higher rate of venous thromboembolism (VTE) (3.9% vs. 0.6%, HR 6.11 [2.46–15.16]; p=0.001), major bleeding (2.9% vs. 0.5%, HR 5.38 [1.95–14.84]; p=0.001), and serious cardiac arrhythmias (2.6% vs. 0.9%, HR 2.25 [1.07–4.73]; p=0.033). During follow-up, between discharge and end of follow-up, COVID-19 patients did not experience a higher risk of adverse cardiovascular outcomes (composite of CV death, any MI, ischemic stroke, systemic arterial thrombosis, VTE, heart failure hospitalization, or any serious arrhythmia) compared to patients without (HR 0.80; [0.53–1.21]; p=0.298). Conclusions At 1-year follow-up, COVID-19 was not associated with an increased risk of cardiovascular death but with a higher risk of VTE events, major bleeding, and serious cardiac arrhythmias. COVID-19 was not associated with a higher risk of adverse cardiovascular events during follow-up. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Carlos III Institute, Madrid, Spain

UNISUS study design: a phase 3 superiority study comparing the efficacy, safety, and tolerability of macitentan 75 mg vs macitentan 10 mg in patients with pulmonary arterial hypertension (PAH)

Abstract Background While advances in PAH-specific therapies have substantially improved survival, there is still an unmet need to improve long-term outcomes in PAH. Purpose The UNISUS study is the first head-to-head superiority study in PAH, comparing the time to morbidity or mortality (M/M) with macitentan 75 mg vs macitentan 10 mg in PAH patients. Methods UNISUS, an ongoing multicentre, prospective, double-blind (DB), adaptive, event-driven superiority study randomises PAH patients 1:1 to receive macitentan 75 mg or macitentan 10 mg, with a target enrolment of ∼900 patients. Efficacy and safety are continuously assessed by an independent data monitoring committee (IDMC), who advises on pre-specified adaptive changes in study conduct, including expansion of the study population. An independent clinical event committee adjudicates all M/M events. The initial population was restricted to patients in functional class (FC) II/III, aged 18–75 years and excluded those with portopulmonary hypertension (PoPH) and those who were PAH treatment-naïve or receiving a prostanoid analogue. Stable (≥3 months) background PAH-therapy may be maintained, except for endothelin receptor agonists (ERAs), which must be stopped the day before initiating study drug. The study is comprised of a screening period, a 4-week run-in period (if ERA treatment-naïve or on sub-optimal ERA dose), and an event-driven DB treatment period, followed by a 2-year open-label extension with macitentan 75 mg. Initiation of macitentan 75 mg occurs after a 4-week up-titration step with macitentan 37.5 mg (Figure 1). The primary endpoint is time to first on-treatment M/M event, defined as first of: all-cause death, PAH-related hospitalisation, or PAH-related disease progression (confirmed ≥15% decrease in 6-minute walk distance (6MWD) and either FC worsening or addition of PAH therapy). Other endpoints include change from baseline to Week 24 in 6MWD and PAH-SYMPACT symptom scores; time to PAH-related hospitalisation or death; time to all-cause death (may be supplemented with data from an external control arm derived from the CARE PAH study [NCT04955990]); and the safety and tolerability of the study drugs. Figure 2 shows planned assessments and sub-studies. To maximise patient retention, add-on PAH therapies are allowed after a M/M event and, for patients at risk of withdrawing and unable to attend visits, the investigator may consider options for reduced follow-up. Results After 60 patients had been exposed for ≥8 weeks, the IDMC reviewed unblinded safety/tolerability data and recommended to expand recruitment from the restricted population to the target population (i.e., including patients: with PoPH, in FC II–IV, from any PAH therapy background [including naïve], aged ≥18 years). Conclusion UNISUS is the first head-to-head superiority study in PAH; with over 200 patients enrolled, it is currently recruiting the target population. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Actelion Pharmaceuticals Ltd., a Janssen pharmaceutical company of Johnson &amp; Johnson.

Self-expanding Transcatheter vs Surgical Aortic Valve Replacement in Intermediate-Risk Patients

In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm2 vs 1.8 [0.6] cm2; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.