Leaflet modification before transcatheter aortic valve implantation in patients at risk for coronary obstruction: the ShortCut study.

BACKGROUND AND AIMS: This trial sought to assess the safety and efficacy of ShortCut, the first dedicated leaflet modification device, prior to transcatheter aortic valve implantation (TAVI) in patients at risk for coronary artery obstruction. METHODS: This pivotal prospective study enrolled patients with failed bioprosthetic aortic valves scheduled to undergo TAVI and were at risk for coronary artery obstruction. The primary safety endpoint was procedure-related mortality or stroke at discharge or 7 days, and the primary efficacy endpoint was per-patient leaflet splitting success. Independent angiographic, echocardiographic, and computed tomography core laboratories assessed all images. Safety events were adjudicated by a clinical events committee and data safety monitoring board. RESULTS: Sixty eligible patients were treated (77.0 ± 9.6 years, 70% female, 96.7% failed surgical bioprosthetic valves, 63.3% single splitting and 36.7% dual splitting) at 22 clinical sites. Successful leaflet splitting was achieved in all (100%; 95% confidence interval [CI] 94-100.0%, p<0.001) patients. Procedure time, including imaging confirmation of leaflet splitting, was 30.6 ± 17.9 min. Freedom from the primary safety endpoint was achieved in 59 (98.3%; 95% CI [91.1-100%]) patients, with no mortality and one (1.7%) disabling stroke. At 30 days, freedom from coronary obstruction was 95% (95% CI 86.1-99.0%). Within 90 days, freedom from mortality was 95% (95% CI 86.1-99.0%]), without any cardiovascular deaths. CONCLUSIONS: Modification of failed bioprosthetic aortic valve leaflets using ShortCut was safe, achieved successful leaflet splitting in all patients, and was associated with favorable clinical outcomes in patients at risk for coronary obstruction undergoing TAVI.

AltaValve Atrial Fixation System for the Treatment of Severe Mitral Regurgitation and Mitral Annular Calcification.

Background: Treatment options for patients with mitral regurgitation (MR) and mitral annular calcification (MAC) are limited. The limitations of current transcatheter mitral valve replacement (TMVR) technologies include high screen failure rates, increased risk of left ventricular outflow tract obstruction, and high residual regurgitation. The aim of this study was to evaluate outcomes of TMVR with the AltaValve system (4C Medical, Maple Grove, MN), a supra-annular TMVR with atrial fixation, in patients with severe MR and moderate or severe MAC. Methods: Six patients with moderate or severe MAC who were treated with AltaValve TMVR had procedural and mid-term outcomes available. Results: Technical success was achieved in all patients. Median follow-up was 232 days. At discharge, 80% of patients had none/trace MR, and 20% had mild MR. There was no intraprocedural mortality, device malposition, embolization, or thrombosis. One patient expired 3 days postprocedure due to complications related to the transapical access. All other patients were discharged from the hospital without issues. Echocardiography assessments at 30 days showed complete resolution of MR in all patients, with 1 patient with mild MR and a mean mitral valve gradient of 3.7 ± 1.4 mmHg. All patients were in New York Heart Association Class I/II at 30-day follow-up, showing marked improvement as compared with baseline. Conclusions: In patients with severe MR and severe MAC, the AltaValve TMVR technology may represent a viable treatment option. The atrial fixation minimizes the risk of left ventricular outflow tract obstruction and potentially expands treatable patients, especially in patients with MAC.

Redo-TAVI with the ACURATE neo2 and Prime XL for balloon-expandable transcatheter heart valve failure.

BACKGROUND: There are limited data regarding treatment for failed balloon-expandable transcatheter heart valves (THVs) in redo-transcatheter aortic valve implantation (TAVI). AIMS: We aimed to assess THV performance, neoskirt height and expansion when performing redo-TAVI with the ACURATE platform inside a SAPIEN 3 (S3) compared to redo-TAVI with an S3 in an S3. METHODS: Redo-TAVI was performed on the bench using each available size of the S3, the ACURATE neo2 (ACn2) and the next-generation ACURATE Prime XL (AC XL) implanted at 2 different depths within 20 mm/23 mm/26 mm/29 mm S3s serving as the "failed" index THV. Hydrodynamic testing was performed to assess THV function. Multimodality assessment was performed using photography, X-ray, microcomputed tomography (micro-CT), and high-speed videos. RESULTS: The ACURATE in S3 combinations had favourable hydrodynamic performance compared to the S3 in S3 for all size combinations. In the 20 mm S3, redo-TAVI with the ACn2 had lower gradients compared to the S3 (mean gradient 16.3 mmHg for the ACn2 vs 24.7 mmHg for the 20 mm S3 in 20 mm S3). Pinwheeling was less marked for the ACURATE THVs than for the S3s. On micro-CT, the S3s used for redo-TAVI were underexpanded across all sizes. This was also observed for the ACURATE platform, but to a lesser extent. CONCLUSIONS: Redo-TAVI with an ACn2/AC XL within an S3 has favourable hydrodynamic performance and less pinwheeling compared to an S3 in S3. This comes at the price of a taller neoskirt.

1-Year Outcomes With Fourth-Generation Mitral Valve Transcatheter Edge-to-Edge Repair From the EXPAND G4 Study.

BACKGROUND: The fourth-generation mitral transcatheter edge-to-edge repair (M-TEER) device introduced an improved clip deployment sequence, independent leaflet grasping, and 2 wider clip sizes to tailor the treatment of patients with mitral regurgitation (MR) for a broad range of anatomies. The 30-day safety and effectiveness of the fourth-generation M-TEER device were previously demonstrated. OBJECTIVES: The aim of this study was to evaluate 1-year outcomes in a contemporary, real-world cohort of subjects treated with the MitraClip G4 system. METHODS: EXPAND G4 is an ongoing prospective, multicenter, international, single-arm study that enrolled subjects with primary and secondary MR. One-year outcomes included MR severity (echocardiographic core laboratory assessed), heart failure hospitalization, all-cause mortality, functional capacity (NYHA functional class), and quality of life (Kansas City Cardiomyopathy Questionnaire). RESULTS: A total of 1,164 subjects underwent M-TEER from 2020 to 2022. At 1 year, there was a durable reduction in MR to mild or less in 92.6% and to none or trace in 44.2% (P < 0.0001 vs baseline). Few subjects had major adverse events through 1 year (<2% for myocardial infarction, surgical reintervention, or single-leaflet device attachment). The 1-year Kaplan-Meier estimates for all-cause mortality and heart failure hospitalization were 12.3% and 16.9%. Significant improvements in functional capacity (NYHA functional class I or II in 82%; P < 0.0001 vs baseline) and quality of life (18.5-point Kansas City Cardiomyopathy Questionnaire overall summary score improvement; P < 0.0001) were observed. CONCLUSIONS: M-TEER with the fourth-generation M-TEER device was safe and effective at 1 year, with durable reductions in MR severity to ≤1+ in more than 90% of patients and concomitant improvements in functional status and quality of life.

Transcatheter Edge-to-Edge Repair in 5,000 Patients With Secondary Mitral Regurgitation: COAPT Post-Approval Study.

BACKGROUND: Real-world applicability of the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) randomized controlled trial (RCT) has been debated because of careful patient selection and the contrasting results of the MITRA-FR (Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients with Severe Secondary Mitral Regurgitation) RCT. OBJECTIVES: The COAPT-PAS (COAPT Post-Approval Study) was initiated to assess the safety and effectiveness of the MitraClip in patients with secondary mitral regurgitation (SMR). METHODS: COAPT-PAS is a prospective, single-arm, observational study of 5,000 consecutive patients with SMR treated with the MitraClip at 406 U.S. centers participating in the TVT (Transcatheter Valve Therapy) registry from 2019 to 2020. The 1-year outcomes from the COAPT-PAS full cohort and the COAPT-like and MITRA-FR-like subgroups who met RCT inclusion/exclusion criteria are reported. RESULTS: Patients in the COAPT-PAS had more comorbidities, more severe HF and functional limitations, and less guideline-directed medical therapy than those in the COAPT or MITRA-FR RCTs. Patients in the COAPT-PAS full cohort and the COAPT-like (n = 991) and MITRA-FR-like (n = 917) subgroups achieved a 97.7% MitraClip implant rate, a similar and durable reduction of mitral regurgitation to ≤2+ at 1 year (90.7%, 89.7%, and 86.6%, respectively), a large improvement in quality of life at 1 year (Kansas City Cardiomyopathy Questionnaire +29 COAPT-PAS, +27 COAPT-like, and +33 MITRA-FR-like), faster procedure times, similar or lower clinical event rates compared with the RCTs' MitraClip arms, and lower clinical event rates than the RCTs' guideline-directed medical therapy only arms. One-year heart failure hospitalizations was 18.9% in COAPT-PAS, 19.7% in COAPT-like compared with 24.9% in COAPT-RCT, and 28.7% in COAPT-PAS-MITRA-FR-like compared with 47.4% in MITRA-FR-RCT. CONCLUSIONS: This large, contemporary, real-world study reinforces the safety and effectiveness of the MitraClip System in patients with SMR, including those who met the COAPT or MITRA-FR RCT inclusion/exclusion criteria and patients excluded from the RCTs.

Real-World Outcomes of Fourth-Generation Mitral Transcatheter Repair: 30-Day Results From EXPAND G4.

BACKGROUND: The fourth-generation MitraClip G4 System builds on the previous NTR/XTR system with additional wider clip sizes (NTW and XTW), an independent grasping feature, and an improved clip deployment sequence. OBJECTIVES: The primary objective of this study was to assess the safety and performance of the MitraClip G4 System within a contemporary real-world setting. METHODS: EXPAND G4 is a prospective, multicenter, international, single-arm, postapproval study that enrolled patients with primary (degenerative) mitral regurgitation (MR) and secondary (functional) MR at 60 centers. Follow-up of the full cohort has been conducted through 30 days. Echocardiograms were analyzed by an echocardiography core laboratory. Study outcomes included MR severity, functional capacity measured by NYHA functional class, quality of life measured using the Kansas City Cardiomyopathy Questionnaire, major adverse event rates, and all-cause mortality. RESULTS: In EXPAND G4, 1,141 subjects with primary MR and secondary MR were treated from March 2021 to February 2022. Implantation and acute procedural success rates were 98.0% and 96.2%, respectively, with a mean of 1.4 ± 0.6 clips implanted per subject. MR was significantly reduced at 30 days compared with baseline (98% achieved MR ≤ 2+, and 91% achieved MR ≤ 1+; P < 0.0001). Functional capacity and quality of life were substantially improved, with 83% of patients achieving NYHA functional class I or II. Likewise, an 18-point improvement was observed in Kansas City Cardiomyopathy Questionnaire summary scores compared with baseline. The composite major adverse event rate was 2.7%, and the all-cause death rate was 1.3% at 30 days. CONCLUSIONS: This study demonstrates for the first time the effectiveness and safety of MitraClip G4 System at 30 days in a cohort of >1,000 patients with MR in a contemporary, real-world setting.

Expanding the Spectrum of TEER Suitability: Evidence From the EXPAND G4 Post Approval Study.

BACKGROUND: Anatomical and clinical criteria to define mitral transcatheter edge-to-edge repair (TEER) "unsuitability" have been proposed on the basis of a Heart Valve Collaboratory consensus opinion from physician experience with early-generation TEER devices but lacked an evidence-based approach. OBJECTIVES: The aim of this study was to explore the spectrum of TEER suitability using echocardiographic and clinical outcomes from the EXPAND G4 real-world postapproval study. METHODS: EXPAND G4 is a global, prospective, multicenter, single-arm study that enrolled 1,164 subjects with mitral regurgitation (MR) treated with the MitraClip G4 System. Three groups were defined using the Heart Valve Collaboratory TEER unsuitability criteria: 1) risk of stenosis (RoS); 2) risk of inadequate MR reduction (RoIR); and 3) subjects with baseline moderate or less MR (MMR). A TEER-suitable (TS) group was defined by the absence of these characteristics. Endpoints included independent core laboratory-assessed echocardiographic characteristics, procedural outcomes, MR reduction, NYHA functional class, Kansas City Cardiomyopathy Questionnaire score, and major adverse events through 30 days. RESULTS: Subjects in the RoS (n = 56), RoIR (n = 54), MMR (n = 326), and TS (n = 303) groups had high 30-day MR reduction rates (≤1+: RoS 97%, MMR 93%, and TS 91%; ≤2+: RoIR 94%). Thirty-day improvements in functional capacity (NYHA functional class I or II at 30 days vs baseline: RoS 94% vs 29%, RoIR 88% vs 30%, MMR 79% vs 26%, and TS 83% vs 33%) and quality of life (change in Kansas City Cardiomyopathy Questionnaire score: RoS +27 ± 26, RoIR +16 ± 26, MMR +19 ± 26, and TS +19 ± 24) were safely achieved in all groups, with low major adverse events (<3%) and all-cause mortality (RoS 1.8%, RoIR 0%, MMR 1.5%, and TS 1.3%). CONCLUSIONS: Patients previously deemed TEER unsuitable can be safely and effectively treated with the mitral TEER fourth-generation device.

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

BACKGROUND: 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. OBJECTIVES: We report 3-year outcomes from the multinational, prospective, single-arm CLASP study with analysis by functional MR (FMR) and degenerative MR (DMR). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Five-Year Follow-up after Transcatheter Repair of Secondary Mitral Regurgitation.

BACKGROUND: Data from a 5-year follow-up of outcomes after transcatheter edge-to-edge repair of severe mitral regurgitation, as compared with outcomes after maximal doses of guideline-directed medical therapy alone, in patients with heart failure are now available. METHODS: We randomly assigned patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy to undergo transcatheter edge-to-edge repair plus receive medical therapy (device group) or to receive medical therapy alone (control group) at 78 sites in the United States and Canada. The primary effectiveness end point was all hospitalizations for heart failure through 2 years of follow-up. The annualized rate of all hospitalizations for heart failure, all-cause mortality, the risk of death or hospitalization for heart failure, and safety, among other outcomes, were assessed through 5 years. RESULTS: Of the 614 patients enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of hospitalization for heart failure through 5 years was 33.1% per year in the device group and 57.2% per year in the control group (hazard ratio, 0.53; 95% confidence interval [CI], 0.41 to 0.68). All-cause mortality through 5 years was 57.3% in the device group and 67.2% in the control group (hazard ratio, 0.72; 95% CI, 0.58 to 0.89). Death or hospitalization for heart failure within 5 years occurred in 73.6% of the patients in the device group and in 91.5% of those in the control group (hazard ratio, 0.53; 95% CI, 0.44 to 0.64). Device-specific safety events within 5 years occurred in 4 of 293 treated patients (1.4%), with all the events occurring within 30 days after the procedure. CONCLUSIONS: Among patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite guideline-directed medical therapy, transcatheter edge-to-edge repair of the mitral valve was safe and led to a lower rate of hospitalization for heart failure and lower all-cause mortality through 5 years of follow-up than medical therapy alone. (Funded by Abbott; COAPT ClinicalTrials.gov number, NCT01626079.).

Percutaneous MitraClip Device or Surgical Mitral Valve Repair in Patients With Primary Mitral Regurgitation Who Are Candidates for Surgery: Design and Rationale of the REPAIR MR Trial.

Background The current standard of care for the treatment of patients with primary mitral regurgitation (MR) is surgical mitral valve repair. Transcatheter edge-to-edge repair with the MitraClip device provides a less invasive treatment option for patients with both primary and secondary MR. Worldwide, >150 000 patients have been treated with the MitraClip device. However, in the United States, MitraClip is approved for use only in primary patients with MR who are at high or prohibitive risk for mitral valve surgery. The REPAIR MR (Percutaneous MitraClip Device or Surgical Mitral Valve Repair in Patients With Primary Mitral Regurgitation Who Are Candidates for Surgery) trial is designed to compare early and late outcomes associated with transcatheter edge-to-edge repair with the MitraClip and surgical repair of primary MR in older or moderate surgical risk patients. Methods and Results The REPAIR MR trial is a prospective, randomized, parallel-controlled, open-label multicenter, noninferiority trial for the treatment of severe primary MR (verified by an independent echocardiographic core laboratory). Patients with severe MR and indications for surgery because of symptoms (New York Heart Association class II-IV), or without symptoms with left ventricular ejection fraction ≤60%, pulmonary artery systolic pressure >50 mm Hg, or left ventricular end-systolic diameter ≥40 mm are eligible for the trial provided they meet the moderate surgical risk criteria as follows: (1) ≥75 years of age, or (2) if <75 years of age, then the subject has a Society of Thoracic Surgeons Predicted Risk Of Mortality score of ≥2% for mitral repair (or Society of Thoracic Surgeons replacement score of ≥4%), or the presence of a comorbidity that may introduce a surgery-specific risk. The local surgeon must determine that the mitral valve can be surgically repaired. Additionally, an independent eligibility committee will confirm that the MR can be reduced to mild or less with both the MitraClip and surgical mitral valve repair with a high degree of certainty. A total of 500 eligible subjects will be randomized in a 1:1 ratio to receive the MitraClip device or to undergo surgical mitral valve repair (control group). There are 2 co-primary end points for the trial, both of which will be evaluated at 2 years. Each subject will be followed for 10 years after enrollment. The study has received approval from both the Food and Drug Administration and the Centers for Medicare and Medicaid Services, and enrolled its first subject in July 2020. Conclusions The REPAIR MR trial will determine the safety and effectiveness of transcatheter edge-to-edge repair with the MitraClip in patients with primary MR who are at moderate surgical risk and are candidates for surgical MV repair. The trial will generate contemporary comparative clinical evidence for the MitraClip device and surgical MV repair. Registration https://clinicaltrials.gov/ct2/show/NCT04198870; NCT04198870.

On-Treatment Platelet Reactivity and Ischemic Outcomes in Patients With Diabetes Mellitus: Two-Year Results From ADAPT-DES.

Background Diabetes mellitus and high platelet reactivity (HPR) on clopidogrel are both associated with increased risk of ischemic events after percutaneous coronary intervention, but whether the HPR-associated risk of adverse ischemic events differs by diabetes mellitus status is unknown. Methods and Results ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective, multicenter registry of patients treated with coronary drug-eluting stents. HPR was defined as P2Y12 reaction units >208 by the VerifyNow point-of-care assay. Cox multivariable analysis was used to assess whether HPR-associated risk of major adverse cardiac events (MACE; cardiac death, myocardial infarction, or stent thrombosis) varied for patients with insulin-treated diabetes mellitus (ITDM), non-ITDM, and no diabetes mellitus. Diabetes mellitus and HPR were included in an interaction analysis. Of 8582 patients enrolled, 2429 (28.3%) had diabetes mellitus, of whom 998 (41.1%) had ITDM. Mean P2Y12 reaction units were higher in patients with diabetes mellitus versus without diabetes mellitus, and HPR was more frequent in patients with diabetes mellitus. HPR was associated with consistently increased 2-year rates of MACE in patients with and without diabetes mellitus (Pinteraction=0.36). A significant interaction was present between HPR and non-insulin-treated diabetes mellitus versus ITDM for 2-year MACE (adjusted hazard ratio [HR] for non-ITDM, 2.28 [95% CI, 1.39-3.73] versus adjusted HR for ITDM, 1.02 [95% CI, 0.70-1.50]; Pinteraction=0.01). Conclusions HPR was more common in patients with diabetes mellitus and was associated with an increased risk of MACE in both patients with and without diabetes mellitus. In patients with diabetes mellitus, a more pronounced effect of HPR on MACE was present in lower-risk non-ITDM patients than in higher-risk patients with ITDM. Registration URL: https://clinicaltrials.gov/ct2/show/NCT00638794; Unique identifier: NCT00638794. ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents).

Dual Antiplatelet Therapy Discontinuation, Platelet Reactivity, and Adverse Outcomes After Successful Percutaneous Coronary Intervention.

OBJECTIVES: The purpose of this study was to assess the extent to which the association between premature dual antiplatelet therapy (DAPT) discontinuation and excess risk of thrombotic events varies according to the reason and timing of DAPT discontinuation and whether high on-treatment platelet reactivity (HPR) influences the risk of thrombotic events after premature DAPT discontinuation. BACKGROUND: DAPT after percutaneous coronary intervention (PCI) suppresses platelet reactivity, and HPR on clopidogrel after PCI is associated with an increased risk of thrombotic events. METHODS: ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective, multicenter registry of 8,582 patients successfully treated with coronary drug-eluting stents that assessed HPR on clopidogrel. For patients who discontinued aspirin or clopidogrel at any time during the study, the reasons for discontinuation were systematically categorized. RESULTS: Planned DAPT discontinuation occurred within 2 years in 3,203 (37.3%) patients. One thousand four hundred eighteen (16.5%) patients discontinued DAPT for unplanned reasons, including surgery or trauma (n = 768 [8.9%]), patient nonadherence (n = 321 [3.7%]), bleeding complications (n = 264 [3.1%]), and drug allergy or hypersensitivity (n = 113 [1.3%]). Unplanned but not planned DAPT discontinuation was associated with an increased risk of a major adverse cardiac event (MACE, defined as the composite of cardiac death, myocardial infarction, or stent thrombosis); with highest risk within 3 months after PCI (adjusted HR: 7.65, 95% CI: 2.77-21.10 vs adjusted HR: 2.47, 95% CI: 1.70-3.58 for unplanned DAPT discontinuation ≥3 weeks after PCI). MACE risk after DAPT discontinuation was not moderated by HPR (Pinteraction = 0.91). CONCLUSIONS: In this large-scale all-comers registry, premature DAPT discontinuation for unplanned reasons occurred in approximately 1 of 6 patients after DES implantation and was associated with a markedly increased risk of MACEs. (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents [ADAPT-DES]; NCT00638794).

Long-Term Clinical Impact of Contrast-Associated Acute Kidney Injury Following PCI: An ADAPT-DES Substudy.

OBJECTIVES: This study sought to determine correlates and consequences of contrast-associated acute kidney injury (CA-AKI) on clinical outcomes in patients with or without pre-existing chronic kidney disease (CKD). BACKGROUND: The incidence and impact of CA-AKI on clinical outcomes during contemporary percutaneous coronary intervention (PCI) are not fully defined. METHODS: The ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents) study was a prospective, multicenter registry of 8,582 patients treated with ≥1 drug-eluting stent(s). CA-AKI was defined as a post-PCI increase in serum creatinine of >0.5 mg/dL or a relative increase of ≥25% compared with pre-PCI. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2. The primary endpoint was the 2-year rate of net adverse clinical events (NACE): All-cause mortality, myocardial infarction (MI), definite or probable stent thrombosis, or major bleeding. RESULTS: Of 7287 (85%) patients with evaluable data, 476 (6.5%) developed CA-AKI. In a multivariable model, older age, female sex, Caucasian race, congestive heart failure, diabetes, hypertension, CKD, presentation with ST-segment elevation MI, Killip class II to IV, radial access, intra-aortic balloon pump use, hypotension, and number of stents were independent predictors of CA-AKI. The 2-year NACE rate was higher in patients with CA-AKI (adjusted HR: 1.88; 95% CI: 1.42-2.49), as was each component of NACE (all-cause mortality, HR: 1.77; 95% CI: 1.22-2.55; MI, HR: 1.67; 95% CI: 1.18-2.36; definite/probable stent thrombosis, HR: 1.71; 95% CI: 1.10-2.65; and major bleeding, HR: 1.38; 95% CI: 1.06-1.80). Compared with the CA-AKI-/CKD- group, the CA-AKI+/CKD- (HR: 1.83; 95% CI: 1.33-2.52), CA-AKI-/CKD+ (HR: 1.56; 95% CI: 1.15-2.13), CA-AKI+/CKD+ (HR: 3.29; 95% CI: 1.92-5.67), and maintenance dialysis (HR: 2.67; 95% CI: 1.65-4.31) groups were at higher risk of NACE. CONCLUSIONS: CA-AKI was relatively common after contemporary PCI and was associated with increased 2-year rates of NACE. Patients with pre-existing CKD were at particularly high risk for NACE after CA-AKI.

Association Between Transcatheter Aortic Valve Replacement for Bicuspid vs Tricuspid Aortic Stenosis and Mortality or Stroke Among Patients at Low Surgical Risk.

Importance: There are limited data on outcomes of transcatheter aortic valve replacement (TAVR) for bicuspid aortic stenosis in patients at low surgical risk. Objective: To compare the outcomes of TAVR with a balloon-expandable valve for bicuspid vs tricuspid aortic stenosis in patients who are at low surgical risk. Design, Setting, and Participants: Registry-based cohort study of patients undergoing TAVR at 684 US centers. Participants were enrolled in the Society of Thoracic Surgeons (STS)/American College of Cardiology Transcatheter Valve Therapies Registry from June 2015 to October 2020. Among 159 661 patients (7058 bicuspid, 152 603 tricuspid), 37 660 patients (3243 bicuspid and 34 417 tricuspid) who were at low surgical risk (defined as STS risk score <3%) were included in the analysis. Exposures: TAVR for bicuspid vs tricuspid aortic stenosis. Main Outcomes and Measures: Coprimary outcomes were 30-day and 1-year mortality and stroke. Secondary outcomes included procedural complications and valve hemodynamics. Results: Among 159 661 patients (7058 bicuspid; 152 603 tricuspid), 3168 propensity-matched pairs of patients with bicuspid and tricuspid aortic stenosis at low surgical risk were analyzed (mean age, 69 years; 69.8% men; mean [SD] STS-predicted risk of mortality, 1.7% [0.6%] for bicuspid and 1.7% [0.7%] for tricuspid). There was no significant difference between the bicuspid and tricuspid groups' rates of death at 30 days (0.9% vs 0.8%; hazard ratio [HR], 1.18 [95% CI, 0.68-2.03]; P = .55) and at 1 year (4.6% vs 6.6%; HR, 0.75 [95% CI, 0.55-1.02]; P = .06) or stroke at 30 days (1.4% vs 1.2%; HR, 1.14 [95% CI, 0.73-1.78]; P = .55) and at 1 year (2.0% vs 2.1%; HR 1.03 [95% CI, 0.69-1.53]; P = .89).There were no significant differences between the bicuspid and tricuspid groups in procedural complications, valve hemodynamics (aortic valve gradient: 13.2 mm Hg vs 13.5 mm Hg; absolute risk difference [RD], 0.3 mm Hg [95% CI, -0.9 to 0.3 mm Hg]), and moderate or severe paravalvular leak (3.4% vs 2.1%; absolute RD, 1.3% [95% CI, -0.6% to 3.2%]). Conclusions and Relevance: In this preliminary, registry-based study of propensity-matched patients at low surgical risk who had undergone TAVR for aortic stenosis, patients treated for bicuspid vs tricuspid aortic stenosis had no significant difference in mortality or stroke at 30 days or 1 year. Because of the potential for selection bias and absence of a control group treated surgically for bicuspid aortic stenosis, randomized trials are needed to adequately assess the efficacy and safety of transcatheter aortic valve replacement for bicuspid aortic stenosis in patients at low surgical risk.

Sex-Specific Outcomes of Transcatheter Mitral-Valve Repair and Medical Therapy for Mitral Regurgitation in Heart Failure.

OBJECTIVES: This study sought to assess the sex-specific outcomes in patients with heart failure (HF) with 3+ and 4+ secondary mitral regurgitation (SMR) treated with transcatheter mitral valve repair (TMVr) plus guideline-directed medical therapy (GDMT) versus GDMT alone in the COAPT trial. BACKGROUND: The impact of sex in patients with HF and severe SMR treated with TMVr with the MitraClip compared with GDMT alone is unknown. METHODS: Patients were randomized 1:1 to TMVr versus GDMT alone. Two-year outcomes were examined according to sex. RESULTS: Among 614 patients, 221 (36.0%) were women. Women were younger than men and had fewer comorbidities, but reduced quality of life and functional capacity at baseline. In a joint frailty model accounting for the competing risk of death, the 2-year cumulative incidence of the primary endpoint of all HF hospitalizations (HFH) was higher in men compared with women treated with GDMT alone. However, the relative reduction in HFHs with TMVr was greater in men (HR: 0.43; 95% CI: 0.34-0.54) than women (HR: 0.78; 95% CI: 0.57-1.05) (Pinteraction = 0.002). A significant interaction between TMVr versus GDMT alone treatment and time was present for all HFHs in women (HR: 0.57; 95% CI: 0.39-0.84, and HR: 1.39; 95% CI: 0.83-2.33 between 0-1 year and 1-2 years after randomization, respectively, Pinteraction = 0.007) but not in men (HR: 0.48; 95% CI: 0.36-0.64, and HR: 0.33; 95% CI: 0.21-0.51; Pinteraction = 0.16). Female sex was independently associated with a lower adjusted risk of death at 2 years (HR: 0.64; 95% CI: 0.46-0.90; P = 0.011). TMVr consistently reduced 2-year mortality compared with GDMT alone, irrespective of sex (Pinteraction = 0.99). CONCLUSIONS: In the COAPT trial, TMVr with the MitraClip resulted in improved clinical outcomes compared with GDMT alone, irrespective of sex. However, the impact of TMVr in reducing HFH was less pronounced in women compared with men beyond the first year after treatment. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Tria] [COAPT]; NCT01626079).

Stent Expansion Indexes to Predict Clinical Outcomes: An IVUS Substudy From ADAPT-DES.

OBJECTIVES: The aim of this study was to evaluate various stent expansion indexes to determine the best predictor of clinical outcomes. BACKGROUND: Numerous intravascular ultrasound (IVUS) studies have shown minimum stent area (MSA) to be the most powerful predictor of future events. METHODS: ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective, multicenter registry of 8,582 patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents. Native coronary artery lesions treated with IVUS-guided PCI with final analyzable IVUS were included. Ten stent expansion indexes (MSA, MSA/vessel area at MSA site, conventional stent expansion [MSA/average of proximal and distal reference luminal area], minimum stent expansion using Huo-Kassab or linear model accounting for vessel tapering, stent asymmetry [minimum/maximum stent diameter within the entire stent], stent eccentricity [smallest minimum/maximum stent diameter at a single slice within the stent], IVUS-XPL [Impact of intravascular Ultrasound Guidance on Outcomes of Xience Prime Stents in Long Lesions] criteria, ULTIMATE [Intravascular Ultrasound Guided Drug Eluting Stents Implantation in "All-Comers" Coronary Lesions] criteria, and ILUMIEN IV criteria) were evaluated for their associations with lesion-specific 2-year clinically driven target lesion revascularization (TLR) or definite stent thrombosis. RESULTS: Overall, 2,140 lesions in 1,831 patients were included; final MSA measured 6.2 ± 2.4 mm2. Among the 10 stent expansion indexes, only MSA/vessel area at the MSA site was independently associated with 2-year clinically driven TLR or definite stent thrombosis (hazard ratio: 0.77; 95% confidence interval: 0.59-0.99; P = 0.04) after adjusting for morphologic and procedural parameters. CONCLUSIONS: In this IVUS-guided PCI cohort with excellent final MSA overall, stent/vessel area at the MSA site, an index of relative stent expansion, was superior to absolute MSA and other expansion indexes in predicting 2-year clinically driven TLR or definite stent thrombosis.

2-Year Outcomes for Transcatheter Repair in Patients With Mitral Regurgitation From the CLASP Study.

OBJECTIVES: This study reports 2-year outcomes from the multicenter, prospective, single-arm CLASP study with functional mitral regurgitation (FMR) and degenerative MR (DMR) analysis. BACKGROUND: Transcatheter repair is a favorable option to treat MR. Long-term prognostic impact of the PASCAL transcatheter valve repair system in patients with clinically significant MR remains to be established. METHODS: Patients had clinically significant MR ≥3+ as evaluated by the echocardiographic core laboratory and were deemed candidates for transcatheter repair by the heart team. Assessments were performed by clinical events committee to 1 year (site-reported thereafter) and core laboratory to 2 years. RESULTS: A total of 124 patients (69% FMR, 31% DMR) were enrolled with a mean age of 75 years, 56% were male, 60% were New York Heart Association functional class III to IVa, and 100% had MR ≥3+. At 2 years, Kaplan-Meier estimates showed 80% survival (72% FMR, 94% DMR) and 84% freedom from heart failure (HF) hospitalization (78% FMR, 97% DMR), with 85% reduction in annualized HF hospitalization rate (81% FMR, 98% DMR). MR ≤1+ was achieved in 78% of patients (84% FMR, 71% DMR) and MR ≤2+ was achieved in 97% (95% FMR, 100% DMR) (all p < 0.001). Left ventricular end-diastolic volume decreased by 33 ml (p < 0.001); 93% of patients were in New York Heart Association functional class I to II (p < 0.001). CONCLUSIONS: The PASCAL repair system demonstrated sustained favorable outcomes at 2 years in FMR and DMR patients. Results showed high survival and freedom from HF rehospitalization rates with a significantly reduced annualized HF hospitalization rate. Durable MR reduction was achieved with evidence of left ventricular reverse remodeling and significant improvement in functional status. The CLASP IID/IIF randomized pivotal trial is ongoing.