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.

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.

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.

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.

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).

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.

Incidence and standardised definitions of mitral valve leaflet adverse events after transcatheter mitral valve repair: the EXPAND study.

BACKGROUND: An independent panel of experts reviewed all investigator-reported cases of mitral valve leaflet adverse events (LAE) after MitraClip NTR/XTR in the EXPAND study. AIMS: We aimed to report the findings of the expert panel and standardise definitions for LAE. METHODS: Standard definitions for different types of LAE were formulated and events adjudicated after detailed review by the expert panel. RESULTS: Enrolling centres reported LAE in 35 cases, 11 leaflet injuries (9 tears, 2 perforations) and 24 single leaflet device attachment (SLDA). The panel confirmed LAE in 20 cases (2.0% incidence), 18 patients had SLDA and 4 had leaflet injury (2 cases had both SLDA and injury). Leaflet injury occurred during device implant and resulted in surgical valve replacement or death. SLDA-alone events were identified during implant (n=2), pre-discharge (n=7) or at 30 days of follow-up (n=7) and were resolved (≤2+ residual MR) with additional clips in 75% of cases. CONCLUSIONS: Mitral valve repair with MitraClip NTR/XTR is safe. The rate of LAE is lower than previously reported using older-generation devices. The proposed definitions and findings will help to differentiate leaflet injury from inadequate leaflet insertion and SLDA and provide guidance for consistent diagnosis of LAE post MitraClip implantation.

3-Year Outcomes of Transcatheter Mitral Valve Repair in Patients With Heart Failure.

BACKGROUND: In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, transcatheter mitral valve repair (TMVr) resulted in fewer heart failure hospitalizations (HFHs) and lower mortality at 24 months in patients with heart failure (HF) with mitral regurgitation (MR) secondary to left ventricular dysfunction compared with guideline-directed medical therapy (GDMT) alone. OBJECTIVES: This study determined if these benefits persisted to 36 months and if control subjects who were allowed to cross over at 24 months derived similar benefit. METHODS: This study randomized 614 patients with HF with moderate-to-severe or severe secondary MR, who remained symptomatic despite maximally tolerated GDMT, to TMVr plus GDMT versus GDMT alone. The primary effectiveness endpoint was all HFHs through 24-month follow-up. Patients have now been followed for 36 months. RESULTS: The annualized rates of HFHs per patient-year were 35.5% with TMVr and 68.8% with GDMT alone (hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.37 to 0.63; p < 0.001; number needed to treat (NNT) = 3.0; 95% CI: 2.4 to 4.0). Mortality occurred in 42.8% of the device group versus 55.5% of control group (HR: 0.67; 95% CI: 0.52 to 0.85; p = 0.001; NNT = 7.9; 95% CI: 4.6 to 26.1). Patients who underwent TMVr also had sustained 3-year improvements in MR severity, quality-of-life measures, and functional capacity. Among 58 patients assigned to GDMT alone who crossed over and were treated with TMVr, the subsequent composite rate of mortality or HFH was reduced compared with those who continued on GDMT alone (adjusted HR: 0.43; 95% CI: 0.24 to 0.78; p = 0.006). CONCLUSIONS: Among patients with HF and moderate-to-severe or severe secondary MR who remained symptomatic despite GDMT, TMVr was safe, provided a durable reduction in MR, reduced the rate of HFH, and improved survival, quality of life, and functional capacity compared with GDMT alone through 36 months. Surviving patients who crossed over to device treatment had a prognosis comparable to those originally assigned to transcatheter therapy. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation [COAPT]; NCT01626079).

Outcomes of transcatheter mitral valve repair for secondary mitral regurgitation by severity of left ventricular dysfunction.

BACKGROUND: In the COAPT trial, transcatheter mitral valve repair with the MitraClip plus maximally tolerated guideline-directed medical therapy (GDMT) improved clinical outcomes compared with GDMT alone in symptomatic patients with heart failure (HF) and 3+ or 4+ secondary mitral regurgitation (SMR) due to left ventricular (LV) dysfunction. AIMS: In this COAPT substudy, we sought to evaluate two-year outcomes in HF patients with reduced LV ejection fraction (HFrEF; LVEF ≤40%) versus preserved LVEF (HFpEF; LVEF >40%) and in those with severe (LVEF ≤30%) versus moderate (LVEF >30%) LV dysfunction. METHODS: The principal effectiveness outcome was the two-year rate of death from any cause or HF hospitalisations (HFH). Subgroup analysis with interaction testing was performed according to baseline LVEF; 472 patients (82.1%) had HFrEF (mean LVEF 28.0%±6.2%; range 12% to 40%) and 103 (17.9%) had HFpEF (mean LVEF 46.6%±4.9%; range 41% to 65%), while 292 (50.7%) had severely depressed LVEF (LVEF ≤30%; mean LVEF 23.9%±3.8%) and 283 (49.3%) had moderately depressed LVEF (LVEF >30%; mean LVEF 39.0%±6.8%). RESULTS: The two-year rate of death or HFH was 56.7% in patients with HFrEF and 53.4% with HFpEF (HR 1.16, 95% CI: 0.86-1.57, p=0.32). MitraClip reduced the two-year rate of death or HFH in patients with HFrEF (HR 0.50, 95% CI: 0.39-0.65) and HFpEF (HR 0.60, 95% CI: 0.35-1.05), pint=0.55. MitraClip was consistently effective in reducing the individual endpoints of mortality and HFH, improving MR severity, quality of life, and six-minute walk distance in patients with HFrEF, HFpEF, LVEF ≤30%, and LVEF >30%. CONCLUSIONS: In the COAPT trial, among patients with HF and 3+ or 4+ SMR who remained symptomatic despite maximally tolerated GDMT, the MitraClip was consistently effective in improving survival and health status in patients with severe and moderate LV dysfunction and those with preserved LVEF.

Stent Thrombosis Risk Over Time on the Basis of Clinical Presentation and Platelet Reactivity: Analysis From ADAPT-DES.

OBJECTIVES: The aim of this study was to determine the risk period for increased stent thrombosis (ST) after percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS) and whether this increased risk is related to high platelet reactivity (HPR). BACKGROUND: ST risk after PCI is higher among patients with ACS than those with stable ischemic heart disease. When ST risk is highest in patients with ACS and how that is affected by HPR is unknown. METHODS: Using the ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) registry, ST rates during 2-year follow-up post-PCI with drug-eluting stents were compared among patients presenting with ACS (myocardial infarction [MI] or unstable angina) or stable ischemic heart disease (non-ACS). Landmark analyses were done at 30 days and 1 year post-PCI. Platelet reactivity on aspirin and clopidogrel post-PCI was assessed using VerifyNow assays. RESULTS: Of 8,582 patients, 2,063 presented with MI, 2,370 with unstable angina, and 4,149 with non-ACS. Incidence rates of HPR were 48.0%, 43.3%, and 39.8%, respectively (p < 0.001). Within the first 30 days post-PCI, patients presenting with MI had increased ST risk compared with patients with non-ACS (hazard ratio [HR]: 4.52; 95% confidence interval [CI]: 2.01 to 10.14; p < 0.001). After 30 days, relative ST risks were progressively lower and no longer significant between groups (31 days to 1 year post-PCI: HR: 1.97; 95% CI: 0.80 to 4.85; >1 year post-PCI: HR: 0.89; 95% CI: 0.27 to 2.92). The elevated ST risk in patients with MI within 30 days was largely confined to those with HPR on clopidogrel (HR: 5.77; 95% CI: 2.13 to 15.63; p < 0.001). CONCLUSIONS: Among patients undergoing PCI, rates of ST during 2-year follow-up were highest in those with MI and lowest in those with non-ACS. Increased ST risk in patients with MI was greatest in the first 30 days post-PCI and was observed predominantly among those with increased HPR on clopidogrel. These findings emphasize the importance of adequate P2Y12 inhibition after MI, especially within the first 30 days after stent implantation.

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

OBJECTIVES: The authors report the CLASP (Edwards PASCAL Transcatheter Mitral Valve Repair System Study) expanded experience, 1-year outcomes, and analysis by functional mitral regurgitation (FMR) and degenerative mitral regurgitation (DMR). BACKGROUND: The 30-day results from the CLASP study of the PASCAL transcatheter valve repair system for clinically significant mitral regurgitation (MR) have been previously reported. METHODS: Eligible patients had symptomatic MR ≥3+, were receiving optimal medical therapy, and were deemed candidates for transcatheter mitral repair by the local heart team. Primary endpoints included procedural success, clinical success, and major adverse event rate at 30 days. Follow-up was continued to 1 year. RESULTS: One hundred nine patients were treated (67% FMR, 33% DMR); the mean age was 75.5 years, and 57% were in New York Heart Association functional class III or IV. At 30 days, there was 1 cardiovascular death (0.9%), MR ≤1+ was achieved in 80% of patients (77% FMR, 86% DMR) and MR ≤2+ in 96% (96% FMR, 97% DMR), 88% of patients were in New York Heart Association functional class I or II, 6-min walk distance had improved by 28 m, and Kansas City Cardiomyopathy Questionnaire score had improved by 16 points (p < 0.001 for all). At 1 year, Kaplan-Meier survival was 92% (89% FMR 96% DMR) with 88% freedom from heart failure hospitalization (80% FMR, 100% DMR), MR was ≤1+ in 82% of patients (79% FMR, 86% DMR) and ≤2+ in 100% of patients, 88% of patients were in New York Heart Association functional class I or II, and Kansas City Cardiomyopathy Questionnaire score had improved by 14 points (p < 0.001 for all). CONCLUSIONS: The PASCAL transcatheter valve repair system demonstrated a low complication rate and high survival, with robust sustained MR reduction accompanied by significant improvements in functional status and quality of life at 1 year. (The CLASP Study Edwards PASCAL Transcatheter Mitral Valve Repair System Study [CLASP]; NCT03170349).

Predictors of Clinical Response to Transcatheter Reduction of Secondary Mitral Regurgitation: The COAPT Trial.

BACKGROUND: Transcatheter mitral valve repair with the MitraClip results in marked clinical improvement in some but not all patients with secondary mitral regurgitation (MR) and heart failure (HF). OBJECTIVES: This study sought to evaluate the clinical predictors of a major response to treatment in the COAPT trial. METHODS: Patients with HF and severe MR who were symptomatic on maximally tolerated guideline-directed medical therapy (GDMT) were randomly assigned to MitraClip plus GDMT or GDMT alone. Super-responders were defined as those alive without HF hospitalization and with ≥20-point improvement in the Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS) score at 12 months. Responders were defined as those alive without HF hospitalization and with a 5 to <20-point KCCQ-OS improvement at 12 months. Nonresponders were those who either died, were hospitalized for HF, or had <5-point improvement in KCCQ-OS at 12 months. RESULTS: Among 614 enrolled patients, 41 (6.7%) had missing KCCQ-OS data and could not be classified. At 12 months, there were 79 super-responders (27.2%), 55 responders (19.0%), and 156 nonresponders (53.8%) in the MitraClip arm compared with 29 super-responders (10.2%), 46 responders (16.3%), and 208 nonresponders (73.5%) in the GDMT-alone arm (overall p < 0.0001). Independent baseline predictors of clinical responder status were lower serum creatinine and KCCQ-OS scores and treatment assignment to MitraClip. MR grade and estimated right ventricular systolic pressure at 30 days were improved to a greater degree in super-responders and responders but not in nonresponders. CONCLUSIONS: Baseline predictors of clinical super-responders in patients with HF and severe secondary MR in the COAPT trial were lower serum creatinine, KCCQ-OS score and MitraClip treatment. Improved MR severity and reduced right ventricular systolic pressure at 30 days are associated with a long-term favorable clinical response after transcatheter mitral valve repair. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [COAPT]; NCT01626079).

Impact of high on-treatment platelet reactivity on outcomes following PCI in patients on hemodialysis: An ADAPT-DES substudy.

OBJECTIVES: We sought to compare clinical outcomes after percutaneous coronary intervention (PCI) in patients on versus not on hemodialysis (HD) and examine whether high on-treatment platelet reactivity (HPR) further impacts outcomes among patients on HD. BACKGROUND: Both chronic kidney disease (CKD) and HPR are predictors of major adverse cardiac events (MACE) after PCI. METHODS: Two-year outcomes of patients from the prospective, multicenter ADAPT-DES study (N = 8,582) were analyzed according to HD status at enrollment. All patients underwent platelet function testing with the VerifyNow assay; HPR on clopidogrel was defined as P2Y12 reaction units (PRU) >208. RESULTS: Compared with non-HD patients, patients on HD (n = 85) had significantly higher baseline PRU (median 254 vs. 188, p = .001) and more frequently had HPR (61.7% vs. 42.5%, p < .001). HD was associated with increased 2-year rates of MACE (death, myocardial infarction (MI) or definite stent thrombosis (ST); 23.4% vs. 10.7%, p < .001). HD was also strongly associated with 2-year overall mortality, cardiac death, MI, target vessel revascularization, major bleeding, stroke and ST. Following adjustment for HPR and other covariates, HD was independently associated with overall mortality, MI, ST, and major bleeding at 2 years. The relationship between HD status and 2-year MACE was consistent in patients with and without HPR (Pinteraction = .78). CONCLUSIONS: Nearly two-thirds of patients on HD exhibited HPR on clopidogrel, and both HD and HPR were independently associated with 2-year adverse outcomes after DES implantation. However, the deleterious impact of HD on clinical outcomes was present in both patients with and without HPR.

Impact of Smoking on Platelet Reactivity and Clinical Outcomes After Percutaneous Coronary Intervention: Findings From the ADAPT-DES Study.

BACKGROUND: Smoking is a potent risk factor for coronary artery disease; however, prior studies describe increased platelet inhibition with clopidogrel among smokers, and some studies report improved outcomes among smokers, a finding described as the smoker's paradox. This study assessed the relationship between platelet reactivity and clinical outcomes after percutaneous coronary interventions among current smokers and nonsmokers. METHODS: ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective, multicenter registry of patients treated with coronary drug-eluting stents. Platelet reactivity was assessed by the VerifyNow point-of-care assay; high on-treatment platelet reactivity (HPR) was defined as P2Y12 reaction units >208. A propensity-adjusted multivariable analysis was performed to determine the relationship between current smoking, platelet reactivity, and subsequent adverse events. RESULTS: Among 8582 patients, 22.6% were active smokers at the time of their percutaneous coronary intervention procedure. Current smokers were younger and had fewer comorbidities compared with nonsmokers. Current smokers had lower mean P2Y12 reaction units and lower rates of HPR compared with nonsmokers. Current smokers had similar rates of adverse events compared with nonsmokers. HPR was associated with higher rates of adverse events for both smokers and nonsmokers; however, there was evidence of interaction between smoking status and the effect of HPR. Smokers with HPR had significantly higher rates of stent thrombosis. Adverse event rates were highest among current smokers with HPR. CONCLUSIONS: Current smoking was associated with lower P2Y12 reaction units and lower rates of HPR on average; however, the combination of current smoking and HPR was associated with high rates of stent thrombosis. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00638794.

Association Between Hypertension, Platelet Reactivity, and the Risk of Adverse Events After Percutaneous Coronary Intervention (From the ADAPT-DES Study).

Hypertension is associated with vascular and endothelial dysfunction that may result in a greater propensity for reactive platelets to cause thrombosis. We sought to assess whether the risk of major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI) in patients with on-clopidogrel residual high platelet reactivity (HPR) varies in patients with versus without hypertension. Assessment of dual antiplatelet therapy with drug eluting stents (ADAPT-DES) was a prospective, multicenter registry of patients successfully treated with coronary drug-eluting stents (DES). HPR was defined as P2Y12 reaction units (PRU) >208, as assessed by the VerifyNow point-of-care assay. Multivariable Cox proportional hazards regression was used to assess whether the adjusted association between HPR and 2-year risk of MACE (cardiac death, myocardial infarction [MI], or stent thrombosis) was different in patients with versus without hypertension. A total of 6833 of 8582 patients (79.6%) had a history of hypertension. Patients with compared with those without hypertension were older, more likely to have other cardiovascular risk factors, and had higher PRU (190.1 ± 97.3 vs 179.5 ± 94.3; p <0.0001). Patients with hypertension had significantly higher 2-year rates of MACE (7.0% vs 4.4%, p <0.001), all-cause death (4.2% vs 2.5%, p = 0.001), and MI (5.2% vs 3.2%, p <0.001), and had nominally higher rates of stent thrombosis (1.0% vs 0.5%, p = 0.059). A significant interaction was present between hypertension and HPR regarding 2-year MACE risk (adjusted hazard ratio for HPR vs no HPR 1.38, 95% confidence interval 1.14 to 1.68 for patients with hypertension vs 0.81, 95% confidence interval 0.50 to 1.33 for patients without hypertension, p = 0.046). In conclusion, following successful PCI with DES, 2-year MACE rates are increased in patients with both hypertension and residual HPR on clopidogrel. HPR had a greater effect on the risk of adverse events among patients with versus without hypertension.