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Drug-coated balloons (DCB) have shown promising results for the treatment of in-stent restenosis (ISR) and small vessel disease (SVD). However, data comparing the treatment efficacy of different DCBs are limited.Methods and Results: AGENT Japan is a prospective randomized controlled trial that compares the Agent balloon coated with a low-dose formulation of paclitaxel (2 μg/mmData from this study demonstrate good clinical outcomes with the Agent DCB when used to treat patients with SVD or ISR.

Background Drug-coated balloon (DCB) technology was developed as an alternative treatment for obstructive coronary artery disease (CAD) and in-stent restenosis (ISR). Management of coronary ISR is clinically challenging and frequently encountered in practice. The Agent DCB uses an inactive excipient to effectively deliver a targeted, therapeutic dose of paclitaxel to the vessel wall. Study Design AGENT IDE is a prospective, multicenter, randomized controlled trial to evaluate superiority of the Agent DCB to balloon angioplasty in treating patients with ISR. A total of 480 patients with ISR of a previously treated lesion length 2.0 mm to ≤4.0 mm will be initially randomized. Subjects presenting with recent myocardial infarction (MI), complex lesions, or thrombus in the target vessel will be excluded. An adaptive group sequential design with one formal interim analysis for sample size re-estimation will be conducted, and the sample size may be increased to a maximum of 600 subjects. The primary endpoint is the rate of 12-month target lesion failure (TLF; composite of any ischemia-driven revascularization of the target lesion (TLR), target vessel related MI, or cardiac death) and will be tested for superiority in the test arm against the control. Functional status and general health-related quality of life will be measured by changes in the EQ-5D scores. Subjects will be followed for 5 years following the index procedure. Conclusion This study will prospectively evaluate the safety and efficacy of Agent DCB in patients treated for coronary ISR.

ImportanceLong-term follow-up after transcatheter aortic valve replacement (TAVR) is of interest given that longitudinal data on mortality and durability of transcatheter heart valves are limited. The REPRISE III (Repositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus Valve System—Randomized Clinical Evaluation) randomized clinical trial compared the mechanically expanded Lotus valve with the self-expanding CoreValve/EvolutR TAVR platforms.ObjectiveTo describe the final 5-year outcomes of the REPRISE III trial.Design, Setting, and ParticipantsThis prespecified secondary analysis assessed the final 5-year clinical, functional, and echocardiographic outcomes of 912 patients from the REPRISE III trial, which was conducted at 55 centers in North America, Europe, and Australia between September 22, 2014, and December 24, 2015. Patients had high risk for aortic stenosis or severe or symptomatic aortic stenosis. Data were analyzed from September 22, 2014, to May 21, 2021.InterventionLotus valve or CoreValve/EvolutR TAVR platforms.Main Outcomes and MeasuresValve Academic Research Consortium-2 end points, hemodynamic measures, functional status, and health status were examined through the 5-year follow-up.ResultsA total of 912 patients (mean [SD] age, 82.8 [7.3] years; 463 women [50.8%]) were randomized to either the Lotus valve group (n = 607) or CoreValve/EvolutR group (n = 305), with a baseline Society of Thoracic Surgeons risk score of 6.8%. Clinical follow-up data from the REPRISE III trial were available for 581 patients (95.7%) in the Lotus valve group and 285 patients (93.4%) in the CoreValve/EvolutR group. At 5 years, the cumulative event rate for all-cause mortality was 50.9% in the Lotus valve group vs 52.8% in the CoreValve/EvolutR group (P = .59). Disabling stroke was less frequent with the Lotus valve vs CoreValve/EvolutR (cumulative event rates, 8.3% vs 12.2%; P = .04), whereas the cumulative event rates for overall stroke were similar in both groups (14.1% vs 15.3%; P = .38). Insertion of a new permanent pacemaker (38.9% vs 27.3%; P P = .007) were more common in the Lotus valve group than in the CoreValve/EvolutR group. A smaller proportion of patients who received the Lotus valve experienced valve malpositioning (0% vs 2.6%; P P P 2 vs 1.42 [0.42] cm2; P = .10). After 5 years, the proportion of patients with moderate or greater paravalvular leak was not significantly higher with the CoreValve/EvolutR than with the Lotus valve (1.9% vs 0%; P = .31); however, the proportion of patients with mild paravalvular leak was higher in the CoreValve/EvolutR group compared with the Lotus valve group (23.1% vs 7.8%; P = .006). Long-term, similar improvements in New York Heart Association class and Kansas City Cardiomyopathy Questionnaire score were observed in both groups.Conclusions and RelevanceThe REPRISE III trial found that, at 5 years, the clinical outcomes of the Lotus valve were comparable to those of the CoreValve/EvolutR and that the Lotus valve was safe and effective.Trial RegistrationClinicalTrials.gov Identifier: NCT02202434

Background: For patients with symptomatic atrial fibrillation (AF), physicians typically offer AF ablation for symptom relief; however, patients often anticipate/expect a life free from anticoagulation. This belief puts patients at increased risk of stroke due to the potential for asymptomatic AF postablation if anticoagulation is ceased contrary to clinical guidelines. Although the WATCHMAN device has been FDA-approved to decrease the risk of thromboembolism from the left atrial appendage (LAA) in patients with an appropriate rationale to avoid oral anticoagulation, it has not been well-studied following AF ablation. Additionally, there are limited data comparing the WATCHMAN device to direct oral anticoagulants. The OPTION study will investigate whether LAA closure with the WATCHMAN FLX device is a reasonable alternative to oral anticoagulation following percutaneous catheter ablation for nonvalvular AF. Trial design: OPTION is a multinational, multicenter, prospective randomized clinical trial. Patients with a CHA2DS2-VASc of ≥2 in men or ≥3 in women and who underwent a AF catheter ablation procedure between 90 and 180 days prior to randomization (sequential) or are planning to have catheter ablation within 10 days of randomization (concomitant) will be randomized in a 1:1 allocation of WATCHMAN FLX vs control. Control patients will start or continue market-approved oral anticoagulation for the duration of the trial. A total of 1600 patients were randomized from 130 global investigational sites. Follow-up for both device and control patients will occur at 3, 12, 24, and 36 months. The primary effectiveness noninferiority endpoint is stroke (ischemic or hemorrhagic), all-cause death, or systemic embolism at 36 months. The primary safety superiority endpoint is nonprocedural bleeding through 36 months (International Society on Thrombosis and Haemostasis [ISTH] major bleeding or clinically relevant nonmajor bleeding). The secondary noninferiority endpoint is ISTH major bleeding through 36 months (including procedural bleeding). Conclusions: This trial will assess the safety and efficacy of WATCHMAN FLX in a postablation contemporary clinical AF patient population at risk of stroke.

Background Transcatheter aortic valve implantation (TAVI) has become standard treatment for elderly patients with symptomatic severe aortic valve stenosis. The ACURATE neo AS study evaluates 30-day and 1-year clinical and hemodynamic outcomes in patients treated with the ACURATE neo2 valve. Methods The primary endpoint of this single-arm multicenter study is 30-day all-cause mortality. Other key endpoints include device performance, echocardiographic measures assessed by an independent core laboratory, and VARC-2 clinical efficacy and safety endpoints through 12 months. Results The study enrolled 120 patients (mean age 82.1 ± 4.0 years; 67.5% female, mean baseline STS score 4.8 ± 3.8%). The VARC-2 composite safety endpoint at 30 days occurred in 13.3% of patients. All-cause mortality was 3.3% at 30 days and 11.9% at 1 year. The 30-day stroke rate was 2.5% (disabling stroke 1.7%); there were no new strokes between 30 days and 12 months. The rate of permanent pacemaker implantation was 15.0% (18/120) at 30 days and 17.8% (21/120) at 1 year. No patients required re-intervention for valve-related dysfunction and there were no cases of valve thrombosis or endocarditis. Patients demonstrated significant improvement in mean aortic valve gradient (baseline 38.9 ± 13.1 mmHg, 1 year 7.8 ± 3.5 mmHg; P Conclusions One-year outcomes from the ACURATE neo AS study support the safety and performance of TAVI with the ACURATE neo2 valve. Graphic Abstract

Background: Left atrial appendage (LAA) occlusion provides an alternative to oral anticoagulation for thromboembolic risk reduction in patients with nonvalvular atrial fibrillation. Since regulatory approval in 2015, the WATCHMAN device has been the only LAA closure device available for clinical use in the United States. The PINNACLE FLX study (Protection Against Embolism for Nonvalvular AF Patients: Investigational Device Evaluation of the Watchman FLX LAA Closure Technology) evaluated the safety and effectiveness of the next-generation WATCHMAN FLX LAA closure device in patients with nonvalvular atrial fibrillation in whom oral anticoagulation is indicated, but who have an appropriate rationale to seek a nonpharmaceutical alternative. Methods: This was a prospective, nonrandomized, multicenter US Food and Drug Administration study. The primary safety end point was the occurrence of one of the following events within 7 days after the procedure or by hospital discharge, whichever was later: death, ischemic stroke, systemic embolism, or device- or procedure-related events requiring cardiac surgery. The primary effectiveness end point was the incidence of effective LAA closure (peri-device flow ≤5 mm), as assessed by the echocardiography core laboratory at 12-month follow-up. Results: A total of 400 patients were enrolled. The mean age was 73.8±8.6 years and the mean CHA 2 DS 2 -VASc score was 4.2±1.5. The incidence of the primary safety end point was 0.5% with a 1-sided 95% upper CI of 1.6%, meeting the performance goal of 4.2% ( P P Conclusions: LAA closure with this next-generation LAA closure device was associated with a low incidence of adverse events and a high incidence of anatomic closure. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02702271.

Background: SYNERGY is a thin-strut, platinum-chromium metal alloy stent with an ultrathin abluminal everolimus-eluting bioabsorbable polymer. EVOLVE II was a global randomized controlled trial that enrolled 1,684 patients treated with either a SYNERGY or durable polymer PROMUS Element Plus (PE+) everolimus-eluting stent, including 155 patients from Japanese sites. This substudy analyzed 5-year clinical outcomes in the Japanese and non-Japanese cohorts. Methods and Results: Patients aged ≥18 years with ≤3 native coronary artery lesions (reference vessel diameter ≥2.25–≤4.00 mm; length ≤34 mm) in ≤2 major vessels were randomized 1 : 1 to receive either SYNERGY (n=74 patients in Japan) or PE+ (n=81 patients in Japan). Five-year target lesion failure (TLF) was observed in 8.3% SYNERGY- and 11.2% PE+-treated patients (P=0.54). There were no cardiac deaths, and rates of target lesion revascularization and myocardial infarction were comparable between treatment arms. One patient in the SYNERGY arm experienced a very late definite stent thrombosis (ST); no ST occurred in the PE+ arm (P=0.30). Despite differences in baseline clinical and lesion characteristics, the 5-year TLF rates were not significantly different in SYNERGY-treated patients either in (8.3%) or outside (14.8%) Japan (P=0.14). Conclusions: In Japanese patients with coronary artery disease, SYNERGY showed comparable efficacy to PE+, with low rates of adverse events over 5 years. Similarly, 5-year clinical outcomes were favorable in Japanese vs. non-Japanese patients implanted with SYNERGY.

Background High blood pressure (BP) is a major risk factor for cardiovascular disease (CVD). Consumption of dark chocolate, which is high in flavonoids that may reduce CVD risk, is an attractive intervention to reduce to BP. Additionally, the use of mobile health (mHealth) technologies (eg, telehealth, smartphones, and wearable devices) can improve outcomes in patients with CVD. Objective The purpose of this study was to investigate the impact of dark chocolate intake on BP, subject use of mHealth, and integration of mHealth into a clinical trial. Methods The COCOA-BP (ChOcolate COnsumption And Blood Pressure) study was a prospective, single-center, pre-/postintervention study that enrolled 62 healthy volunteers. The study consisted of 3 phases: smartwatch/smart BP monitor familiarization and washout from chocolate (week 1); control (week 2); and intervention (weeks 3 and 4). During the intervention phase, subjects consumed 50 g of dark chocolate per day. The primary endpoint was change in resting systolic BP between the intervention and control phases. Additional endpoints included device accuracy and correlation with physical activity. Results Mean resting systolic BP was 116.4 mm Hg before chocolate intake among 62 participants (mean age 37 years; 61% female). After chocolate intake, mean resting systolic BP was 116.0 mm Hg (difference –0.4; P = .69). These findings suggest that 2 weeks of dark chocolate intake did not reduce resting systolic BP. There was poor agreement between mHealth device and standard (nurse-performed) measurements. Conclusion In this study, short-term dark chocolate intake did not seem to reduce BP. mHealth technology shows great potential for use in clinical studies, but challenges related to device accuracy and compliance need to be addressed.

Transcatheter aortic-valve replacement (TAVR) for the treatment of aortic stenosis can lead to embolization of debris. Capture of debris by devices that provide cerebral embolic protection (CEP) may reduce the risk of stroke.We randomly assigned patients with aortic stenosis in a 1:1 ratio to undergo transfemoral TAVR with CEP (CEP group) or without CEP (control group). The primary end point was stroke within 72 hours after TAVR or before discharge (whichever came first) in the intention-to-treat population. Disabling stroke, death, transient ischemic attack, delirium, major or minor vascular complications at the CEP access site, and acute kidney injury were also assessed. A neurology professional examined all the patients at baseline and after TAVR.A total of 3000 patients across North America, Europe, and Australia underwent randomization; 1501 were assigned to the CEP group and 1499 to the control group. A CEP device was successfully deployed in 1406 of the 1489 patients (94.4%) in whom an attempt was made. The incidence of stroke within 72 hours after TAVR or before discharge did not differ significantly between the CEP group and the control group (2.3% vs. 2.9%; difference, -0.6 percentage points; 95% confidence interval, -1.7 to 0.5; P = 0.30). Disabling stroke occurred in 0.5% of the patients in the CEP group and in 1.3% of those in the control group. There were no substantial differences between the CEP group and the control group in the percentage of patients who died (0.5% vs. 0.3%); had a stroke, a transient ischemic attack, or delirium (3.1% vs. 3.7%); or had acute kidney injury (0.5% vs. 0.5%). One patient (0.1%) had a vascular complication at the CEP access site.Among patients with aortic stenosis undergoing transfemoral TAVR, the use of CEP did not have a significant effect on the incidence of periprocedural stroke, but on the basis of the 95% confidence interval around this outcome, the results may not rule out a benefit of CEP during TAVR. (Funded by Boston Scientific; PROTECTED TAVR ClinicalTrials.gov number, NCT04149535.).

In the U.S. Food and Drug Administration (FDA) clinical trials of left atrial appendage (LAA) closure, a postimplantation peridevice leak (PDL) of ≤5 mm (PDL≤5) was accepted as sufficient LAA "closure." However, the clinical consequences of these PDLs on subsequent thromboembolism are poorly characterized.We sought to assess the impact of PDL≤5 on clinical outcomes after implantation of the Watchman device.Using combined data from the FDA studies PROTECT-AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation), PREVAIL (Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation vs Long Term Warfarin Therapy), and CAP2 (Continued Access to PREVAIL), we assessed patients with successful device implantation for PDL by means of protocol-mandated transesophageal echocardiograms (TEEs) at 45 days and 1 year. Five-year outcomes were assessed as a function of the absence or presence of PDL≤5.The cohort included 1,054 patients: mean age 74 ± 8.3 years, 65% male, and CHAPDL≤5 at 1 year after percutaneous LAA closure with the Watchman device are associated with increased thromboembolism, driven by increased nondisabling stroke, but similar mortality. (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation [PROTECT-AF; NCT00129545]; Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation vs Long Term Warfarin Therapy [PREVAIL; NCT01182441]; Continued Access to PREVAIL [CAP2; NCT01760291]).

Background A transapical (TA) approach to transcatheter aortic valve replacement (TAVR) may be used when a transfemoral (TF) approach is not feasible. The CHANGE neo TA study evaluated patients treated in routine clinical practice via TA-TAVR with the ACURATE neo bioprosthetic aortic valve. Methods and results This single-arm post-market study had a planned enrolment of 200 subjects; enrolment was terminated early due to declining TA-TAVR procedures at participating centers. Final enrolment was 107 patients (mean age: 79.3 years; 54.2% female; mean STS score at baseline: 6.2%). The mortality rate in the intent-to-treat population was 11.2% at 30 days (primary endpoint) and 25.6% at 12 months. The VARC-2 composite endpoint for 30-day safety occurred in 24.3% of patients. Six patients (5.6%) received a permanent pacemaker within 30 days. Site-reported echocardiographic data showed early improvements in mean aortic valve gradient (baseline: 38.8 [SD 13.1] mmHg, discharge: 6.7 [SD 3.7] mmHg) and effective orifice area (baseline: 0.7 [SD 0.2] cm2, discharge: 1.9 [SD 0.6] cm2), and the discharge rate of paravalvular regurgitation was low (74.7% none/trace, 24.2% mild, 1.1% severe). Conclusions TA-TAVR with the ACURATE neo valve system yields acceptable clinical outcomes, providing an alternative for patients with aortic stenosis who are not candidates for TF-TAVR.

PROMUS Element (PE) Plus post-approval study was a large prospective, observational, all-comers study designed to evaluate the safety and performance of a thin-strut platinum chromium everolimus-eluting PE Plus stent in everyday clinical practice. A total of 2,683 "real-world" patients with limited clinical or anatomic exclusion criteria were enrolled at 52 clinical sites in the United States. The study met its primary end point of 12-month cardiac death or myocardial infarction (CD/MI) compared with a prespecified performance goal (p

Background A transapical (TA) approach to transcatheter aortic valve replacement (TAVR) may be used when a transfemoral (TF) approach is not feasible. The CHANGE neo TA study evaluated patients treated in routine clinical practice via TA-TAVR with the ACURATE neo bioprosthetic aortic valve. Methods and results This single-arm post-market study had a planned enrolment of 200 subjects; enrolment was terminated early due to declining TA-TAVR procedures at participating centers. Final enrolment was 107 patients (mean age: 79.3 years; 54.2% female; mean STS score at baseline: 6.2%). The mortality rate in the intent-to-treat population was 11.2% at 30 days (primary endpoint) and 25.6% at 12 months. The VARC-2 composite endpoint for 30-day safety occurred in 24.3% of patients. Six patients (5.6%) received a permanent pacemaker within 30 days. Site-reported echocardiographic data showed early improvements in mean aortic valve gradient (baseline: 38.8 [SD 13.1] mmHg, discharge: 6.7 [SD 3.7] mmHg) and effective orifice area (baseline: 0.7 [SD 0.2] cm2, discharge: 1.9 [SD 0.6] cm2), and the discharge rate of paravalvular regurgitation was low (74.7% none/trace, 24.2% mild, 1.1% severe). Conclusions TA-TAVR with the ACURATE neo valve system yields acceptable clinical outcomes, providing an alternative for patients with aortic stenosis who are not candidates for TF-TAVR.

Background: Prolonged dual antiplatelet therapy (DAPT) after percutaneous coronary intervention is associated with increased bleeding, despite a reduced incidence of ischemic events. The SYNERGY everolimus-eluting stent is a thin-strut platinum-chromium stent that elutes everolimus from a thin abluminal layer of bioabsorbable polymer. These design elements may facilitate rapid endothelialization and enable shorter-duration DAPT. Methods: EVOLVE Short DAPT prospectively evaluated the safety of 3-month DAPT in high bleeding risk patients treated with the SYNERGY everolimus-eluting stent, enrolling 2009 patients at 110 global sites. Patients with acute myocardial infarction or complex lesions were excluded. After percutaneous coronary intervention, patients were required to take DAPT (aspirin+P2Y 12 inhibitor) for 3 months, except those on chronic anticoagulation in whom aspirin was optional. Patients free of events (stroke, myocardial infarction, revascularization, and stent thrombosis) who discontinued P2Y 12 inhibitor at 3 months, but continued aspirin, and had at least 1 year of follow-up or an end point event were included in the primary analysis. Two powered coprimary end points were (1) death/myocardial infarction compared with a historical control and (2) study stent-related definite/probable stent thrombosis compared to a performance goal. Results: The analysis population consisted of 1487 patients. The adjusted rate of death/myocardial infarction between 3 and 15 months was 5.6% among patients receiving 3-month DAPT versus 5.7% patients in the 12-month DAPT control (propensity adjusted difference=−0.12%; 97.5% upper bound=1.63% which was less than the prespecified margin of 2.52; P non-inferiority =0.0016). The rate of study stent-related stent thrombosis between 3-15 months was 0.2% in the 3-month DAPT group (97.5% upper bound=0.63%; P =0.0005 for comparison to 1% performance goal). Conclusions: Favorable rates of ischemic outcomes were observed among selected high bleeding risk patients undergoing percutaneous coronary intervention with the SYNERGY everolimus-eluting stent who tolerated 3 months of P2Y 12 inhibitor and then discontinued it, supporting the safety of abbreviated DAPT with this stent platform. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02605447.

OBJECTIVES The EVOLVE 48 study evaluated the safety and effectiveness of the SYNERGY 48 mm stent for the treatment of long lesions. BACKGROUND Clinical evidence supporting the use of very long stents during percutaneous coronary intervention (PCI) is limited. The bioabsorbable polymer SYNERGY stent has shown good long-term data in a broad population of patients undergoing PCI. METHODS Patients with lesion length >34- ≤44 mm and reference vessel diameter (RVD) ≥2.5- ≤ 4.0 mm were enrolled in this prospective, multicenter, single-arm study. The primary endpoint was 12-month target lesion failure (TLF; composite of target lesion revascularization [TLR], target-vessel myocardial infarction [TV-MI], or cardiac death) compared to a prespecified performance goal (PG). RESULTS A total of 100 patients with mean lesion length of 35.34 ± 7.15 mm (26 patients with lesion length > 40 mm) and mean RVD 2.72 ± 0.44 mm were enrolled. Moderate to severe calcification was present in 30% of the patients and 89% had pre-TIMI flow grade 3. The rates of technical and clinical procedural success were 100%. One-year TLF was observed in 4.1% patients compared to a prespecified PG of 19.5% (95% upper confidence bound = 9.1%; p

Background Minorities and women are underrepresented in cardiovascular research. Whether their higher enrollment can be predicted or influences research site performance is unclear. Methods We evaluated 104 sites that enrolled 4,184 patients in the U.S. Platinum Diversity (PD) and Promus Element Plus (PE Plus) studies (2012 to 2016). Research sites were ranked from lowest to highest minority and female enrollment, respectively. United States Census Bureau division and core-based statistical area (CBSA) populations were determined for each site and the following study performance metrics compared across quartiles of minority and female enrollment, respectively: (1) study subject enrollment rate (SER), (2) time to first patient enrolled, (3) rate of follow-up visits not done, (4) rate of follow-up visits out of window, and (5) protocol deviation rate (PDR). Multivariable regression was used to predict SER and PDR. Results Minority enrollment varied by region (P = .025) and population (P = .024) with highest recruitment noted in the Pacific, West South Central, South Atlantic, Mid-Atlantic and East North Central divisions. Female enrollment bore no relationship to region (P = .67) or population (P = .40). Median SER was similar in sites withi the highest vs lowest quartile of minority enrollment (SER of 4 vs 5 patients per month, respectively, P =0.78) and highest vs. lowest female enrollment (SER of 4 vs 4, respectively, P = .21). Median PDR was lower in sites within the highest vs lowest minority enrollment (0.23 vs 0.50 PDs per patient per month, respectively, P = .01) and highest vs. lowest female enrollment (0.28 vs. 0.37 PDs per patient per month, respectively, P = .04). However, this relationship did not persist after multivariable adjustment. All other site performance metrics were comparable across quartiles of minority and female enrollment. Conclusions Minority, but not female enrollment, correlated with research site geographic region and surrounding population. High enrollment of minorities and women did not influence study performance metrics. These findings help inform future strategies aimed at increasing clinical trial diversity. Trial Registration The PD and PE Plus studies are registered at www.clinicaltrials.gov under identifiers NCT02240810 and NCT01589978, respectively. Key Points Question: Does the enrollment of more Blacks, Hispanics and women in US cardiovascular research studies influence the overall rate of study subject enrollment and/or other key study site performance metrics and can diverse enrollment be predicted? Findings: In this pooled analysis of 104 sites that enrolled 4,184 patients in the Platinum Diversity and Promus Element Plus Post-Approval Studies, we found that the enrollment of higher proportions of underrepresented minorities and women was univariately associated with lower protocol deviation rates while having no effect on other site performance metrics. A site's geographic location and surrounding population predicted minority, but not female enrollment. Meaning: These findings suggest that cardiovascular research subject diversity may be predicted from site characteristics and enhanced without compromising key study performance metrics. These insights help inform future strategies aimed at improving clinical trial diversity.

BACKGROUND In this analysis of the EWOLUTION registry, we evaluated the incidence, relevance and predictors of device-related thrombus in a large multi-center real-world cohort undergoing LAAc with the WATCHMAN device. METHODS AND RESULTS We analyzed the 835 patients who underwent percutaneous LAA closure with the WATCHMAN device in the EWOLUTION registry in whom at least one TEE follow up was performed. Patients were 74 ± 9 y/o and were at high risk for stroke and bleeding (CHA2DS2-VASC-Score 4.3 ± 1.7; HAS-BLED-Score 2.3 ± 1.2). Device-related thrombus was detected in 4.1% (34/835) after a median of 54 days (IQR 42-111 days) with 91.2% (31/34) being detected within 3 months after the procedure or at the time of first TEE. Hereby DRT occurred irrespective of postprocedural anticoagulation. Patients with DRT more frequently had long-standing, non-paroxysmal atrial fibrillation (82.4 vs. 64.9%, p

Objective We evaluated 1-year outcomes after platinum chromium everolimus-eluting stents (PtCr-EES) in small versus non-small coronary arteries within a large, diverse sample of men, women, and minorities. Background There exists limited outcomes data on the use of second-generation drug-eluting stent to treat small diameter coronary arteries. Methods We pooled patients from the PLATINUM Diversity and PROMUS Element Plus stent registries. Small-vessel percutaneous coronary intervention (SV-PCI) was defined as ≥1 target lesion with reference vessel diameter (RVD) ≤2.5 mm. Endpoints included major adverse cardiac event (MACE; death, myocardial infarction [MI] or target vessel revascularization [TVR]), target vessel failure (TVF; death related to the target vessel, target vessel MI or TVR) and definite/probable stent thrombosis (ST). Multivariable Cox regression was used to risk-adjust outcomes. Results We included 4,155/4,182 (99%) patients with available RVD, of which 1,607 (39%) underwent small-vessel PCI. SV-PCI was not associated with increased MACE (adjHR 1.02; 95%CI 0.81-1.30) or TVF (adjHR 1.07; 95%CI 0.82-1.39). MI risk was lower in white men compared to women and minorities, both in the setting of SV-PCI (adjHR 0.41; 95%CI 0.23-0.74 and adjHR 0.39; 95%CI 0.20-0.75, respectively) and for non-SV-PCI (adjHR 0.61; 95%CI 0.38-0.99 and adjHR 0.45; 95%CI 0.27-0.74, respectively). There was no significant interaction between RVD and sex or minority status for any endpoint. Conclusion In a large diverse contemporary PCI outcomes database, SV-PCI with PtCr-EES was not associated with increased MACE or TVR and did not account for the increased MI risk noted in women and minorities compared to white men.

Objectives The authors sought to evaluate 1-year clinical outcomes with the Lotus valve (Boston Scientific, Marlborough, Massachusetts) in a large international, multicenter prospective registry including patients eligible for transcatheter aortic valve replacement (TAVR) based on heart team consensus. Background TAVR is a safe and effective treatment for severe aortic valve stenosis; however, limited data are available on TAVR with the repositionable and fully retrievable Lotus valve in unrestricted contemporary clinical practice. Methods The RESPOND (Repositionable Lotus Valve System—Post-Market Evaluation of Real World Clinical Outcomes) study enrolled 1,014 patients; 996 patients were implanted with the Lotus valve (mean age 80.8 years, 50.8% female, mean STS score 6.0 ± 6.9%). The primary endpoint was all-cause mortality in the intent-to-treat population at 30 days and 1 year. An Extension cohort of 50 patients was treated with the Lotus valve with Depth Guard including a modified delivery system. Mortality and stroke were independently adjudicated. An independent core laboratory assessed echocardiographic data. Results One-year clinical follow-up was available for 99.9% of Lotus valve-treated patients. At 1 year, the all-cause mortality rate was 11.7% and 4.1% of patients had experienced a disabling stroke. The permanent pacemaker implantation rate was 32% (37% among pacemaker-naive patients). Echocardiographic data at 1 year were available for core laboratory assessment in 62.6% of patients. Paravalvular leak was absent or trace in 94.5%, mild in 5.1%, and moderate in 0.4% of patients. Data from the Extension cohort confirmed good clinical outcomes at 30 days with an 18% permanent pacemaker rate (20% among pacemaker-naive patients). Conclusions One-year outcomes from the RESPOND study confirm the safety and efficacy of the Lotus valve when used in routine clinical practice. (Repositionable Lotus Valve System—Post-Market Evaluation of Real World Clinical Outcomes [RESPOND]; NCT02031302)

Objectives The goal of this analysis was to evaluate the final 5-year safety and effectiveness of the PROMUS Element platinum-chromium everolimus-eluting stent in unselected patients treated in routine clinical practice. Background The prospective, open-label PROMUS Element™ European Post-Approval Surveillance Study (PE-PROVE) enrolled 1,010 "real-world" patients who received the PROMUS Element stent. Adverse event rates were low at 1-year, and the incidence of stent thrombosis was 0.6%. Methods The primary endpoint was target vessel failure (TVF; overall and PE stent-related), a composite of cardiac death, myocardial infarction (MI) related to the target vessel, or target vessel revascularization (TVR) at 1-year post-implantation. Five-year clinical outcomes were evaluated in overall as well as high-risk patient subgroups. Results The overall 5-year TVF rate was 14.9%, with 7.0% being related to the study stent. Cardiac death, MI and TVR related to the study stent occurred in 0.5%, 3.2%, and 5.7%, respectively. Stent thrombosis through 5-year follow-up was 1.0%. The rates of overall and study stent related TVF were numerically higher in patients with medically treated diabetes, long lesions (≥28 mm), and small diameter vessels (≤2.5 mm) compared to the overall study population. Additionally, favorable stent thrombosis rates through 5 years were reported for the PROMUS Element stent in these high-risk subgroups. Conclusions The final 5-year data from the PE-PROVE study demonstrate favorable outcomes and low rates of adverse events with the PE stent when used in "real-world" patients with coronary artery disease.

Aims: The EVOLVE China randomised study sought to evaluate the clinical safety and effectiveness of the SYNERGY bioabsorbable polymer-coated everolimus-eluting stent (EES) for the treatment of patients with coronary heart disease in China. Methods and results: Eligible patients with de novo native coronary artery lesions were randomised (1: 1) to receive the SYNERGY or PROMUS Element Plus stent. The primary endpoint was in-stent late loss at nine months. Secondary endpoints included death, MI, revascularisation, and stent thrombosis up to 12 months. A total of 412 subjects were randomised (205 SYNERGY; 207 PROMUS Element Plus) at 14 sites in China from October 2013 to July 2014. SYNERGY was non-inferior to PROMUS Element Plus for the primary endpoint of nine-month in-stent late loss: SYNERGY 0.20 +/- 0.33 mm vs. PROMUS Element Plus 0.17 +/- 0.38 mm with an upper one-sided 97.5% confidence interval of the difference (0.10 mm), significantly less than the non-inferiority margin (0.15 mm; pl0.0008). Clinical adverse event rates were low and not significantly different between groups at nine and 12 months (all pg0.05). Conclusions: In the EVOLVE China trial, the SYNERGY bioabsorbable polymer-coated EES was noninferior to the PROMUS Element Plus permanent polymer-coated EES for the primary endpoint of late loss at nine months.

RESPOND is a prospective, single-arm study enrolling 1014 transcatheter aortic valve replacement (TAVR) patients. The objective of this analysis is to assess the impact of cerebral embolic protection (CEP) devices and prosthetic valve repositioning on the risk of neurologic complications in patients treated with the fully repositionable Lotus Valve in the RESPOND postmarket study. Valve repositioning and CEP use were at the operators’ discretion. Stroke events were adjudicated by an independent medical reviewer. This analysis assessed the baseline differences among patients according to CEP use and valve repositioning and evaluated the neurological complications at 72 hours after TAVR, hospital discharge, and 30-day follow-up. A multivariate analysis was performed to identify the potential predictors of stroke. Of the 996 patients implanted with the Lotus Valve (mean age: 80.8 years, 50.8% female, STS score 6.0 ± 6.9), 92 cases (9.2%) used CEP. The overall rate of acute stroke/transient ischemic attack (TIA) was 3.0% at 72 hours after TAVR. The 72-hour stroke/TIA rate was 1.1% in patients who had CEP and 3.2% in those who did not. Use of CEP was associated with a 2.1% absolute reduction in the risk of acute neurological events (relative risk reduction: 65.6%), although the difference was not statistically significant (p = 0.51). Repositioning of the Lotus Valve occurred in 313/996 procedures (31.4%); p = 0.86. The 72-hour rate of stroke/TIA was similar in patients who had valve repositioning (2.9%) compared with those who did not (3.1%; ). The selective use of a CEP device in the RESPOND study was associated with a nonsignificantly lower risk for stroke within 72 hours. The use of the repositioning feature of the Lotus Valve did not increase the stroke risk., Journal of Interventional Cardiology, 2020, ISSN:0896-4327, ISSN:1540-8183

Background As transcatheter aortic valve replacement expands to younger and/or lower risk patients, the long‐term consequences of permanent pacemaker implantation are a concern. Pacemaker dependency and impact have not been methodically assessed in transcatheter aortic valve replacement trials. We report the incidence and predictors of pacemaker implantation and pacemaker dependency after transcatheter aortic valve replacement with the Lotus valve. Methods and Results A total of 912 patients with high/extreme surgical risk and symptomatic aortic stenosis were randomized 2:1 (Lotus:CoreValve) in REPRISE III (The Repositionable Percutaneous Replacement of Stenotic Aortic Valve through Implantation of Lotus Valve System—Randomized Clinical Evaluation) trial. Systematic assessment of pacemaker dependency was pre‐specified in the trial design. Pacemaker implantation within 30 days was more frequent with Lotus than CoreValve. By multivariable analysis, predictors of pacemaker implantation included baseline right bundle branch block and depth of implantation; diabetes mellitus was also a predictor with Lotus. No association between new pacemaker implantation and clinical outcomes was found. Pacemaker dependency was dynamic (30 days: 43%; 1 year: 50%) and not consistent for individual patients over time. Predictors of pacemaker dependency at 30 days included baseline right bundle branch block, female sex, and depth of implantation. No differences in mortality or stroke were found between patients who were pacemaker dependent or not at 30 days. Rehospitalization was higher in patients who were not pacemaker dependent versus patients without a pacemaker or those who were dependent. Conclusions Pacemaker implantation was not associated with adverse clinical outcomes. Most patients with a new pacemaker at 30 days were not dependent at 1 year. Mortality and stroke were similar between patients with or without pacemaker dependency and patients without a pacemaker. Clinical Trial Registration URL : https://www.clinicaltrials.gov/ . Unique identifier NCT 02202434.

Background Gait speed, as a measure of physical function and marker of frailty, is now routinely screened when evaluating patients with aortic stenosis (AS) for transcatheter aortic valve implantation (TAVI). Assessment of physical function is important to identify patients for whom TAVI may be futile and to assign patients to a procedural risk category. After TAVI, patients may exhibit physical resilience (improvement in physical function) or vulnerability (worsening). Characterizing the trajectory and clinical consequences of physical function after TAVI represent knowledge gaps in the field. Purpose Evaluate associations between physical resilience (improved gait speed) vs vulnerability (decline) after TAVI and subsequent death/hospitalization. Methods The REPRISE III trial compared a mechanically-expanded vs a self-expanding valve in 912 high/extreme risk patients with symptomatic AS. Patients (n=587) who underwent valve implantation and who had a gait speed recorded both pre- and 1-year post-TAVI were analyzed. Gait speed is based on the 5m walk test (slow: 5m in >6s, Results A clinically-meaningful improvement (≥0.1m/s), no change (±0.1m/s), or decline (≥0.1/ms) in gait speed 1 year after TAVI was observed in 39%, 36%, and 26% of patients, respectively. Among the 4 groups defined by pre- and 1-year post-TAVI gait speeds, 1 to 2 year mortality or hospitalization rates were: 6.6% (normal/normal), 20.9% (normal/slow), 8.0% (slow/normal), and 21.5% (slow/slow). Adjusted hazard ratios of the 2 models are shown (Table). Table. Outcome by Change in Gait Speed Death/Hospitalization P-value Death P-value Hospitalization P-value Adjusted HR [95% CI] Adjusted HR [95% CI] Adjusted HR [95% CI] Model 1: Baseline/1 year Gait Speed (Normal/Normal (n=150) [referent]) Normal/Slow (n=59) 3.82 [1.61, 9.08] Conclusion These data reveal there is marked heterogeneity in the trajectory of physical function after TAVI and that this trajectory–more so than baseline physical function–is clinically consequential. Identifying and optimizing factors associated with physical resilience after TAVI may improve outcomes. Acknowledgement/Funding Boston Scientific

Background: The thin-strut SYNERGY stent has an abluminal everolimus-eluting bioabsorbable polymer coating designed to facilitate vascular healing and reduce risk of stent thrombosis. In the multicenter, randomized EVOLVE II trial (The EVOLVE II Clinical Trial to Assess the SYNERGY Stent System for the Treatment of Atherosclerotic Lesion[s]), SYNERGY was noninferior to the durable polymer PROMUS Element Plus everolimus-eluting stent for the primary end point of 1-year target lesion failure. Longer-term clinical follow-up will support the relative efficacy and safety of SYNERGY. Methods: Patients with ≤3 native coronary lesions (reference vessel diameter ≥2.25–≤4.00 mm; length ≤34 mm) in ≤2 major epicardial vessels were randomized 1:1 to SYNERGY (N=838) or PROMUS Element Plus (N=846). EVOLVE II included a Diabetes substudy which pooled patients with diabetes mellitus from the randomized controlled trial (n=263) and from a sequential, single-arm substudy (N=203). Results: The 5-year target lesion failure rate was 14.3% for SYNERGY and 14.2% for PROMUS Element Plus ( P =0.91). Landmark analysis demonstrated similar rates of target lesion failure from discharge to 1-year ( P =0.90) and from 1 to 5 years ( P =0.94). Definite/probable stent thrombosis was infrequent in both arms (SYNERGY 0.7% versus PROMUS Element Plus 0.9%; P =0.75). There were no significant differences in the rates of cardiac death, myocardial infarction, or revascularization. Among patients with diabetes mellitus, the target lesion failure rate to 1-year was noninferior to a prespecified performance goal and to 5 years was 17.0%. Conclusions: SYNERGY demonstrated comparable outcomes to PROMUS Element Plus, with low rates of stent thrombosis and adverse events through 5 years of follow-up. Five-year clinical outcomes were favorable in patients with diabetes mellitus. These data support the long-term safety and effectiveness of SYNERGY in a broad range of patients. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01665053.

Background The impact of race/ethnicity on coronary stent outcomes in women is unknown. We compared baseline characteristics, social determinants of health, and 1-year outcomes in female African Americans (AA) and Hispanic/Latinas (HL) versus white women after coronary everolimus-eluting stent implantation in all-comer patients. Methods and Results We pooled 1863 women from the PLATINUM Diversity (n=1057 women) and PROMUS ELEMENT PLUS (n=806 women) postapproval studies, with some overlap in study sites. Social determinants of health data were only available for PLATINUM Diversity. The primary end point was 1-year major adverse cardiac events (death, myocardial infarction, or target vessel revascularization). Outcomes were risk adjusted using multivariate Cox regression. The study sample comprised 1417 white (76.1%, reference group), 296 AA (15.9%), and 107 HL (5.7%) women. AA were older, and both AA and HL had more diabetes mellitus and hypertension than white women. AA had larger reference vessel diameters but less lesion calcification, whereas HL had less lesion tortuosity but more calcification. Compared with white women, there was a trend toward higher unadjusted 1-year major adverse cardiac events in AA (12.0% versus 8.0%; P =0.06) but similar rates in HL (11.0% versus 8.0%; P =0.32), and after risk adjustment, there were no differences (AA women: hazard ratio, 1.47; 95% CI, 1.00–2.17; HL women: hazard ratio, 1.33; 95% CI, 0.71–2.44). AA had a 3-fold higher adjusted risk of 1-year myocardial infarction (hazard ratio, 3.45; 95% CI, 1.72–7.14; P =0.01) and increased risk of target vessel revascularization (hazard ratio, 1.82; 95% CI, 1.10–2.94; P =0.02). Independent predictors of major adverse cardiac events included renal disease, prior myocardial infarction, silent ischemia, history of stroke, and multivessel disease. Conclusions Race and ethnicity confer heterogeneity in women undergoing everolimus-eluting stent implantation. Despite more comorbidities and less favorable social determinants of health, AA and HL women have similar 1-year major adverse cardiac events to white women, although AA women seem to have a higher risk of 1-year myocardial infarction. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT02240810.

Aims: This analysis aimed to evaluate the incidence and predictors of the need for permanent pacemaker (PPM) implantation following implantation of the repositionable and fully retrievable LOTUS Aortic Valve Replacement System. Methods and results: The prospective, single-arm, multicentre REPRISE II study with extended cohort enrolled 250 symptomatic, high surgical risk patients with severe aortic stenosis for transfemoral transcatheter aortic valve implantation (TAVI) with a 23 mm or 27 mm LOTUS valve. Echocardiography, computed tomography, and electrocardiography data were evaluated by independent core labs. Post TAVI, 32.0% (72/225) of pacemaker-naive patients underwent new PPM implantation at 30 days. Most (59/72, 82%) patients were implanted for third-degree atrioventricular block, and >10% overstretch of the LVOT by area was observed in 59.7% (43/72) of PPM patients. Significant independent predictors of PPM at 30 days included baseline RBBB (odds ratio [OR] 12.7, 95% CI: 4.5, 36.2; p 10% (OR 3.4, 95% CI: 1.7, 6.7; p 5 mm depth from LCS; p=0.06). Conclusions: Careful attention to valve sizing and implant depth may help to reduce the rate of PPM with the LOTUS valve.

Aims: The REPRISE IIE trial aimed to evaluate outcomes following transcatheter aortic valve implantation of the fully repositionable and retrievable LOTUS valve with a unique seal designed to minimise paravalvular leak (PVL). Methods and results: This prospective, multicentre study enrolled 250 patients with severe aortic stenosis considered high-risk for surgery by a multidisciplinary Heart Team. An independent clinical events committee adjudicated events per Valve Academic Research Consortium criteria. Mean age was 84 years; 77% were in NYHA Class III/IV. LOTUS valve implantation produced significant haemodynamic improvements at one year without valve embolisation, ectopic valve deployment, or additional valve implantation. Primary endpoints were met as the 30-day mortality rate in the extended cohort (4.4%, N=250), and mean valve gradient in the main cohort (11.5±5.2 mmHg, N=120) were below (p

The PROMUS Element Plus US Post-Approval Study (PE-Plus PAS) was a prospective, open-label, multicenter, observational study designed to examine outcomes in everyday clinical practice in patients treated with everolimus-eluting, platinum-chromium PROMUS Element Plus stents at 52 centers in the United States. This is the first report of results from this large study. The primary end point of the PE-Plus PAS was 12-month cardiac death or myocardial infarction in the more restricted population of "PLATINUM-like" patients pooled from the PE-Plus PAS, PE-PROVE (PROMUS Element European post-approval study), and PLATINUM Workhorse/Small Vessel trials. Additional clinical end points were tested in the overall PE-Plus PAS patient population. Of the 2,683 patients enrolled in PE-Plus PAS, 70% were men, mean age was 64 years, 33% had diabetes, and 29% were "PLATINUM-like." Among the PLATINUM-like patients, 12-month cardiac death or myocardial infarction was 1.8% (33 of 1,855) with an upper 1-sided 95% confidence interval of 2.3%, which was significantly less than the prespecified performance goal of 3.2% (pnoninferiority

Background The Lotus aortic valve system is a new generation transcatheter heart valve (THV) designed with a seal to minimize paravalvular leak (PVL). We evaluated hemodynamic performance, PVL and ventricular function up to 1-year after transcatheter aortic valve replacement (TAVR) using the Lotus THV in patients with severe aortic stenosis. Methods RESPOND was a prospective, single-arm, multicenter registry evaluating outcomes after Lotus TAVR in routine clinical practice. Core Laboratory adjudicated echocardiograms at baseline, discharge and 1-year were analyzed in a subgroup (N=550) of patients with paired transthoracic echocardiography (TTE) at the 3 timepoints. Results Mean effective aortic valve orifice area (EOA) in cm2 increased from 0.74±0.25 at baseline to 1.83±0.46 at discharge and to 1.78±0.45 at 1-year. Mean transvalvular gradient in mmHg was reduced from 38.7±15.2 at baseline to 10.9±4.2 at discharge and to 10.8±5.1 at 1-year. VARC-2 hemodynamic success ([EOA >1.1cm2 for BSA ≥1.6m2 or EOA >0.9cm2 for BSA2; and no moderate or severe PVL) was achieved in 92% and 95% of patients at discharge and 1-year, respectively. Mild or more PVL was seen in 7.3% and 5.5% and moderate or more PVL was seen in 0.6% and 0.4% of patients at discharge and 1-year, respectively. Stroke volume index (mL/m2) increased from 35±10 at baseline to 40±11 at discharge and to 41±11 at 1-year (pRepositionable Lotus Valve System–Post Market Evaluation of Real World Clinical Outcomes [RESPOND]; NCT02031302).

Aims: Patients with bicuspid valves represent a challenging anatomical subgroup for transcatheter aortic valve implantation (TAVI). This analysis evaluated the clinical outcomes of the fully repositionable and retrievable Lotus Valve System in patients with bicuspid aortic valves enrolled in the RESPOND post-market registry. Methods and Results: The prospective, open-label RESPOND study enrolled 1,014 patients at 41 centers in Europe, New Zealand, and Latin America, 31 (3.1%) of whom had bicuspid aortic valves. The mean age in the bicuspid patient cohort was 76.4 years, 64.5% were male, and the baseline STS score was 6.0 ± 10.2. Procedural success was 100%, with no cases of malpositioning, valve migration, embolization, or valve-in-valve. Repositioning was attempted in 10 cases (32.3%). There was one death (3.2%) and one stroke (3.2%) at 30-day follow-up. Mean AV gradient was reduced from 48.7 ± 17.0 mmHg at baseline to 11.8 ± 5.1 mmHg at hospital discharge (P < 0.001); mean effective orifice area (EOA) was increased from 0.6 ± 0.2 cm2 to 1.7 ± 0.4 cm2 (P < 0.001). There were no cases of moderate or severe paravalvular leak (PVL) adjudicated by the core laboratory; four subjects (13.8%) had mild PVL, 5 (17.2%) had trace PVL. The rate of pacemaker (PM) implantation for PM-naive patients was 22.2% (6/27). Conclusions: Data from the RESPOND registry demonstrate good clinical and echocardiographic outcomes up to 1 year postimplantation in patients with bicuspid aortic valves using the repositionable Lotus Valve.

It is unknown if minority enrollment affects research site performance We evaluated 104 sites enrolling 4,184 patients in 2 US coronary stent registries (2012-2016). Sites were grouped into quartiles of low to high % minority enrollment (diversity index: D1: lt 4.8% minorities; D2: 4.9-23%