In vivo fluid dynamics of the Ventura interatrial shunt device in patients with heart failure.

AIMS: Interatrial shunts are under evaluation as a treatment for heart failure (HF); however, their in vivo flow performance has not been quantitatively studied. We aimed to investigate the fluid dynamics properties of the 0.51 cm orifice diameter Ventura shunt and assess its lumen integrity with serial transesophageal echocardiography (TEE). METHODS AND RESULTS: Computational fluid dynamics (CFD) and bench flow tests were used to establish the flow-pressure relationship of the shunt. Open-label patients from the RELIEVE-HF trial underwent TEE at shunt implant and at 6 and 12 month follow-up. Shunt effective diameter (Deff) was derived from the vena contracta, and flow was determined by the continuity equation. CFD and bench studies independently validated that the shunt's discharge coefficient was 0.88 to 0.89. The device was successfully implanted in all 97 enrolled patients; mean age was 70 ± 11 years, 97% were NYHA class III, and 51% had LVEF ≤40%. Patency was confirmed in all instances, except for one stenotic shunt at 6 months. Deff remained unchanged from baseline at 12 months (0.47 ± 0.01 cm, P = 0.376), as did the trans-shunt mean pressure gradient (5.1 ± 3.9 mmHg, P = 0.316) and flow (1137 ± 463 mL/min, P = 0.384). TEE measured flow versus pressure closely correlated (R2 ≥ 0.98) with a fluid dynamics model. At 12 months, the pulmonary/systemic flow Qp/Qs ratio was 1.22 ± 0.12. CONCLUSIONS: When implanted in patients with advanced HF, this small interatrial shunt demonstrated predictable and durable patency and performance.

Impact of heart failure hospitalizations on clinical outcomes after mitral transcatheter edge-to-edge repair: Results from the EXPAND study.

AIM: This analysis aimed to compare the clinical outcomes associated with heart failure (HF) readmissions and to identify associations with HF hospitalizations (HFH) in patients treated with the MitraClip™ NTR/XTR System in the EXPAND study. METHODS AND RESULTS: The global, real-world EXPAND study enrolled 1041 patients with primary or secondary mitral regurgitation (MR) treated with the MitraClip NTR/XTR System. Echocardiograms were analysed by an independent echocardiographic core laboratory. The study population was stratified into HFH and No-HFH groups based on the occurrence of HFH 1 year post-index procedure. Clinical outcomes including MR severity, New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, and all-cause mortality were compared (HFH: n = 181; No-HFH: n = 860). Both groups achieved consistent 1-year MR reduction to ≤1+ (HFH vs. No-HFH: 87.3% vs. 89.5%, p = 0.6) and significant 1-year improvement in KCCQ scores (+16.5 vs. +22.3, p = 0.09) and NYHA functional class. However, more patients in the No-HFH group had 1-year NYHA class ≤II (HFH vs. No-HFH: 67.9% vs. 81.9%, p < 0.01). All-cause mortality at 1 year was 36.8% in the HFH group versus 10.4% in the No-HFH group (p < 0.001). The HFH rate decreased by 63% at 1 year post-M-TEER versus 1 year pre-treatment (relative risk 0.4, p < 0.001). Independent HFH associations were MR ≥2+ at discharge, HFH 1 year prior to treatment, baseline NYHA class ≥III, baseline tricuspid regurgitation ≥2+, and baseline left ventricular ejection fraction ≤40%. CONCLUSIONS: This study reports the impact of HFH on clinical outcomes post-treatment in the EXPAND study. Results demonstrate that the occurrence of HFH was associated with worse 1-year survival, and treatment with the MitraClip system substantially reduced HFH and improved patient symptoms and quality of life.

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.

Interatrial shunt therapy in advanced heart failure: Outcomes from the open-label cohort of the RELIEVE-HF trial.

AIMS: Heart failure (HF) outcomes remain poor despite optimal guideline-directed medical therapy (GDMT). We assessed safety, effectiveness, and transthoracic echocardiographic (TTE) outcomes during the 12 months after Ventura shunt implantation in the RELIEVE-HF open-label roll-in cohort. METHODS AND RESULTS: Eligibility required symptomatic HF despite optimal GDMT with ≥1 HF hospitalization in the prior year or elevated natriuretic peptides. The safety endpoint was device-related major adverse cardiovascular or neurological events at 30 days, compared to a prespecified performance goal. Effectiveness evaluations included the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline, 1, 3, 6, and 12 months and TTE at baseline and 12 months. Overall, 97 patients were enrolled and implanted at 64 sites. Average age was 70 ± 11 years, 97% were in New York Heart Association class III, and half had left ventricular ejection fraction (LVEF) ≤40%. The safety endpoint was achieved (event rate 0%, p < 0.001). KCCQ overall summary score was improved by 12-16 points at all follow-up timepoints (all p < 0.004), with similar outcomes in patients with reduced and preserved LVEF. At 12 months, left ventricular end-systolic and end-diastolic volumes were reduced (p = 0.020 and p = 0.038, respectively), LVEF improved (p = 0.009), right ventricular end-systolic and end-diastolic areas were reduced (p = 0.001 and p = 0.030, respectively), and right ventricular fractional area change (p < 0.001) and tricuspid annular plane systolic excursion (p < 0.001) improved. CONCLUSION: Interatrial shunting with the Ventura device was safe and resulted in favourable clinical effects in patients with HF, regardless of LVEF. Improvements of left and right ventricular structure and function were consistent with reverse myocardial remodelling. These results would support the potential of this shunt device as a treatment for HF.

Regurgitant Volume to LA Volume Ratio in Patients with Secondary MR: The COAPT Trial.

AIMS: The conceptual framework of proportionate versus disproportionate mitral regurgitation (MR) translates poorly to individual patients with heart failure (HF) and secondary MR. A novel index, the ratio of MR severity to left atrial volume (LAV), may identify patients with "disproportionate" MR and a higher risk of events. The objectives, therefore, were to investigate the prognostic impact of MR severity to LAV ratio on outcomes among HF patients with severe secondary MR randomized to transcatheter edge-to-edge repair (TEER) with the MitraClipTM device plus guideline-directed medical therapy (GDMT) vs. GDMT alone in the COAPT trial. METHODS AND RESULTS: The ratio of preprocedural regurgitant volume (RVol) to LAV was calculated from baseline transthoracic echocardiograms. The primary endpoint was 2-year covariate-adjusted rate of HF hospitalization (HFH).Among 567 patients, the median RVol/LAV was 0.67 (IQR 0.48-0.91). In patients randomized to GDMT alone, lower RVol/LAV was independently associated with an increased 2-year risk of HFH (adjHR: 1.77; 95% CI: 1.20-2.63). RVol/LAV was a stronger predictor of adverse outcomes than RVol or LAV alone. Treatment with TEER plus GDMT compared with GDMT alone was associated with lower 2-year rates of HFH both in patients with low and high RVol/LAV (Pinteraction = 0.28). Baseline RVol/LAV ratio was unrelated to 2-year mortality, health status, or functional capacity in either treatment group. CONCLUSIONS: Low RVol/LAV ratio was an independent predictor of 2-year HFH in HF patients with severe MR treated with GDMT alone in the COAPT trial. TEER improved outcomes regardless of baseline RVol/LAV ratio. CLINICAL TRIAL REGISTRATION: Trial Name: Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (The COAPT Trial) (COAPT) ClinicalTrial.gov Identifier: NCT01626079 URL: https://clinicaltrials.gov/ct2/show/NCT01626079.

One-Year Outcomes From the CLASP IID Randomized Trial for Degenerative Mitral Regurgitation.

BACKGROUND: The CLASP IID (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical) trial is the first randomized controlled trial comparing the PASCAL system and the MitraClip system in prohibitive risk patients with significant symptomatic degenerative mitral regurgitation (DMR). OBJECTIVES: The study sought to report primary and secondary endpoints and 1-year outcomes for the full cohort of the CLASP IID trial. METHODS: Prohibitive-risk patients with 3+/4+ DMR were randomized 2:1 (PASCAL:MitraClip). One-year assessments included secondary effectiveness endpoints (mitral regurgitation [MR] ≤2+ and MR ≤1+), and clinical, echocardiographic, functional, and quality-of-life outcomes. Primary safety (30-day composite major adverse events [MAE]) and effectiveness (6-month MR ≤2+) endpoints were assessed for the full cohort. RESULTS: Three hundred patients were randomized (PASCAL: n = 204; MitraClip: n = 96). At 1 year, differences in survival, freedom from heart failure hospitalization, and MAE were nonsignificant (P > 0.05 for all). Noninferiority of the PASCAL system compared with the MitraClip system persisted for the primary endpoints in the full cohort (For PASCAL vs MitraClip, the 30-day MAE rates were 4.6% vs 5.4% with a rate difference of -0.8% and 95% upper confidence bound of 4.6%. The 6-month MR≤2+ rates were 97.9% vs 95.7% with a rate difference of 2.2% and 95% lower confidence bound (LCB) of -2.5%, for, respectively). Noninferiority was met for the secondary effectiveness endpoints at 1 year (MR≤2+ rates for PASCAL vs MitraClip were 95.8% vs 93.8% with a rate difference of 2.1% and 95% LCB of -4.1%. The MR≤1+ rates were 77.1% vs 71.3% with a rate difference of 5.8% and 95% LCB of -5.3%, respectively). Significant improvements in functional classification and quality of life were sustained in both groups (P <0.05 for all vs baseline). CONCLUSIONS: The CLASP IID trial full cohort met primary and secondary noninferiority endpoints, and at 1 year, the PASCAL system demonstrated high survival, significant MR reduction, and sustained improvements in functional and quality-of-life outcomes. Results affirm the PASCAL system as a beneficial therapy for prohibitive-surgical-risk patients with significant symptomatic DMR.

1-Year Outcomes of Transcatheter Edge-to-Edge Repair in Anatomically Complex Degenerative Mitral Regurgitation Patients.

BACKGROUND: Favorable 6-month outcomes from the CLASP IID Registry (Edwards PASCAL transcatheter valve repair system pivotal clinical trial) demonstrated that mitral valve transcatheter edge-to-edge repair with the PASCAL transcatheter valve repair system is safe and beneficial for treating prohibitive surgical risk degenerative mitral regurgitation (DMR) patients with complex mitral valve anatomy. OBJECTIVES: The authors sought to assess 1-year safety, echocardiographic and clinical outcomes from the CLASP IID Registry. METHODS: Patients with 3+ or 4+ DMR who were at prohibitive surgical risk, had complex mitral valve anatomy based on the MitraClip Instructions for Use, and deemed suitable for treatment with the PASCAL system were enrolled prospectively. Safety, clinical, echocardiographic, functional, and quality-of-life outcomes were assessed at 1 year. Study oversight included a central screening committee, echocardiographic core laboratory, and clinical events committee. RESULTS: Ninety-eight patients were enrolled. One-year Kaplan-Meier (KM) estimates of freedom from composite major adverse events, all-cause mortality, and heart failure hospitalization were 83.5%, 89.3%, and 91.5%, respectively. Significant mitral regurgitation (MR) reduction was achieved at 1 year (P < 0.001 vs baseline) including 93.2% at MR ≤2+ and 57.6% at MR ≤1+ with improvements in related echocardiographic measures. NYHA functional class and Kansas City Cardiomyopathy Questionnaire score also improved significantly (P < 0.001 vs baseline). CONCLUSIONS: At 1 year, treatment with the PASCAL system demonstrated safety and significant MR reduction, with continued improvement in clinical, echocardiographic, functional, and quality-of-life outcomes, illustrating the value of the PASCAL system in the treatment of prohibitive surgical risk patients with 3+ or 4+ DMR and complex mitral valve anatomy.

5-Year Prospective Evaluation of Mitral Valve-in-Valve, Valve-in-Ring, and Valve-in-MAC Outcomes: MITRAL Trial Final Results.

BACKGROUND: The MITRAL (Mitral Implantation of Transcatheter Valves) trial is the first prospective trial to evaluate the safety and feasibility of balloon-expandable aortic transcatheter heart valves in patients with failed surgical bioprostheses or annuloplasty rings and severe mitral annular calcification treated with mitral valve-in-valve (MViV), valve-in-ring (MViR), or valve-in-mitral annular calcification (ViMAC). OBJECTIVES: The aim of this study was to evaluate 5-year outcomes among these patients. METHODS: A multicenter prospective study was conducted among patients at high surgical risk at 13 U.S. sites. Patients underwent MViV (n = 30), MViR (n = 30), or ViMAC (n = 31) and were followed annually for 5 years. Kansas City Cardiomyopathy Questionnaire scores were obtained at baseline and follow-up visits. Echocardiograms were analyzed at independent core laboratories. RESULTS: A total of 91 patients underwent transcatheter mitral valve replacement (February 2015 to December 2017). The mean age was 74.3 ± 8.9 years. At 5-year follow-up, the lowest all-cause mortality was observed in the MViV group (21.4%), 94.7% of patients were in NYHA functional class I or II, and the mean mitral gradient was 6.6 ± 2.5 mm Hg. The MViR and ViMAC groups had higher all-cause mortality (65.5% and 67.9%), most survivors were in NYHA functional classes I and II (50% and 55.6%), and mean mitral gradients remained stable (5.8 ± 0.1 and 6.7 ± 2.5 mm Hg). Significant improvements in Kansas City Cardiomyopathy Questionnaire scores were observed when all 3 arms were pooled. CONCLUSIONS: MViV, MViR, and ViMAC procedures were associated with sustained improvement of heart failure symptoms and quality of life among survivors at 5 years. Transcatheter heart valve function remained stable in all 3 groups. Patients treated with MViV had excellent survival at 5 years, whereas survival was lower in the MViR and ViMAC groups, consistent with underlying disease severity. Patients with more residual mitral regurgitation had higher mortality.

Two-Year Outcomes for Tricuspid Repair With a Transcatheter Edge-to-Edge Valve Repair From the Transatlantic TRILUMINATE Trial.

BACKGROUND: Tricuspid regurgitation (TR) is a common and progressive valve disease with significant mortality and hospitalization burden. Tricuspid transcatheter edge-to-edge repair provides a treatment option for high-risk patients with primary and secondary TR. METHODS: The TRILUMINATE trial ([Trial to Evaluate Treatment With Abbott Transcatheter Clip Repair System in Patients With Moderate or Greater Tricuspid Regurgitation]; n=85) is an international, prospective, single-arm, multicenter study to investigate the safety and performance of tricuspid transcatheter edge-to-edge repair with the TriClip implant in patients with symptomatic moderate or greater TR. Echocardiographic assessment was performed at a core laboratory. Outcomes included safety and clinical effectiveness and echocardiographic assessment of TR. RESULTS: At 2 years, TR was reduced to moderate or less in 60% of subjects, and reduction of at least 1 grade was achieved in 85.4% of subjects. TR reduction was sustained in 75% of the patients. While most metrics suggest the majority of favorable remodeling occurred within the first 30 days post-procedure, both right ventricular end diastolic diameter and tricuspid annular plane systolic excursion show signals of continued favorable remodeling through 2 years. Substantial improvements in 6-minute walking distance, New York Heart Association functional class, and Kansas City Cardiomyopathy Questionnaire score were sustained from 30 days to 2 years. Even with low rates of cardiovascular mortality (15.3%) and all-cause mortality (18.7%) noted at 2 years, all-cause hospitalization rate decreased from 1.30 events per patient-year 1 year before device implantation to 0.66 events per patient-year 2 years after the TriClip procedure, representing a reduction of 49% (P<0.0001). CONCLUSIONS: Tricuspid transcatheter edge-to-edge repair using the TriClip implant was found to be safe and effective, with sustained benefits at 2 years in subjects with symptomatic moderate or greater TR. Repair efficacy was durable at 2 years in 75% of the patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03227757.

Changes in Left Ventricular Global Longitudinal Strain in Patients With Heart Failure and Secondary Mitral Regurgitation: The COAPT Trial.

Background Left ventricular (LV) global longitudinal strain (GLS) provides incremental prognostic information over LV ejection fraction in patients with heart failure (HF) and secondary mitral regurgitation. We examined the prognostic impact of LV GLS improvement in this population. Methods and Results The COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial randomized symptomatic patients with HF with severe (3+/4+) mitral regurgitation to transcatheter edge-to-edge repair with the MitraClip device plus maximally tolerated guideline-directed medical therapy (GDMT) versus GDMT alone. LV GLS was measured at baseline and 6-month follow-up. The relationship between the improvement in LV GLS from baseline to 6 months and the composite of all-cause death or HF hospitalization between 6- and 24-month follow-up were assessed. Among 383 patients, 174 (45.4%) had improved LV GLS at 6-month follow-up (83/195 [42.6%] with transcatheter edge-to-edge repair+GDMT and 91/188 [48.4%] with GDMT alone; P=0.25). Improvement in LV GLS was strongly associated with reduced death or HF hospitalization between 6 and 24 months (P<0.009), with similar risk reduction in both treatment arms (Pinteraction=0.40). By multivariable analysis, LV GLS improvement at 6 months was independently associated with a lower risk of death or HF hospitalization (hazard ratio [HR], 0.55 [95% CI, 0.36-0.83]; P=0.009), death (HR, 0.48 [95% CI, 0.29-0.81]; P=0.006), and HF hospitalization (HR, 0.50 [95% CI, 0.31-0.81]; P=0.005) between 6 and 24 months. Conclusions Among patients with HF and severe mitral regurgitation in the COAPT trial, improvement in LV GLS at 6-month follow-up was associated with improved outcomes after both transcatheter edge-to-edge repair and GDMT alone between 6 and 24 months. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079.

Incidence, Predictors, and Outcomes Associated With Worsening Renal Function in Patients With Heart Failure and Secondary Mitral Regurgitation: The COAPT Trial.

Background The incidence and implications of worsening renal function (WRF) after mitral valve transcatheter edge-to-edge repair (TEER) in patients with heart failure (HF) are unknown. Therefore, the aim of this study was to determine the proportion of patients with HF and secondary mitral regurgitation who develop persistent WRF within 30 days following TEER, and whether this development portends a worse prognosis. Methods and Results In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial, 614 patients with HF and severe secondary mitral regurgitation were randomized to TEER with the MitraClip plus guideline-directed medical therapy (GDMT) versus GDMT alone. WRF was defined as serum creatinine increase ≥1.5× or ≥0.3 mg/dL from baseline persisting to day 30 or requiring renal replacement therapy. All-cause death and HF hospitalization rates between 30 days and 2 years were compared in patients with and without WRF. WRF at 30 days was present in 11.3% of patients (9.7% in the TEER plus GDMT group and 13.1% in the GDMT alone group; P=0.23). WRF was associated with all-cause death (hazard ratio [HR], 1.98 [95% CI, 1.3-3.03]; P=0.001) but not HF hospitalization (HR, 1.47 [ 95% CI, 0.97-2.24]; P=0.07) between 30 days and 2 years. Compared with GDMT alone, TEER reduced both death and HF hospitalization consistently in patients with and without WRF (Pinteraction=0.53 and 0.57, respectively). Conclusions Among patients with HF and severe secondary mitral regurgitation, the incidence of WRF at 30 days was not increased after TEER compared with GDMT alone. WRF was associated with greater 2-year mortality but did not attenuate the treatment benefits of TEER in reducing death and HF hospitalization compared with GDMT alone. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079.

Transcatheter Left Atrial Appendage Exclusion: Preclinical and Early Clinical Results With the Laminar Device.

BACKGROUND: The Laminar device rotates and closes the left atrial appendage (LAA) using an integrated ball and lock that excludes and eliminates the LAA pouch. There is a low device surface area, minimizing the risk of peridevice leak (PDL) and device-related thrombus (DRT) formation. OBJECTIVES: This study evaluates the safety and efficacy of the Laminar LAA exclusion device in healthy animals and human subjects with nonvalvular atrial fibrillation at risk of ischemic stroke and systemic thromboembolism. METHODS: The preclinical study implanted the Laminar device into canine subjects that underwent transesophageal echocardiography (TEE) and fluoroscopic evaluation, followed by necropsy and histological assessment at 45 and 150-days post-implant. The early clinical study implanted the device in human subjects, followed to 12 months postimplantation. Procedural success was defined as device implantation in the intended location without residual LAA leak >5 mm as seen by TEE. Safety endpoints included freedom from stroke, systemic embolism, pericardial effusion, or tamponade, life-threatening/major bleeding, or death. RESULTS: The Laminar device was successfully implanted in 10 canines. In all animals at 45 days and 150 days, no PDL or DRT was found, and histological examination showed fully closed LAAs covered with neo-endocardium. The device was successfully implanted in 15 human subjects with no safety events out to 12 months postimplantation. All subjects had successful protocol-defined LAA closure without DRT at 45 days by TEE and computed tomography, which remained stable through 12 months' follow-up. CONCLUSIONS: The preclinical and early clinical results demonstrate a promising safety and efficacy profile for the Laminar LAA exclusion device.

Impact of Malnutrition in Patients With Heart Failure and Secondary Mitral Regurgitation: The COAPT Trial.

BACKGROUND: Although malnutrition is associated with poor prognosis in several diseases, its prognostic impact in patients with heart failure (HF) and secondary mitral regurgitation (SMR) is not understood. OBJECTIVES: The purpose of this study was to assess the prevalence and impact of malnutrition in HF patients with severe SMR randomized to transcatheter edge-to-edge repair (TEER) with the MitraClip plus guideline-directed medical therapy (GDMT) vs GDMT alone in the COAPT trial. METHODS: Baseline malnutrition risk was calculated using the validated geriatric nutritional risk index (GNRI) score. Patients were categorized as having "malnutrition" (GNRI ≤98) vs "no malnutrition" (GNRI >98). Outcomes were assessed through 4 years. The primary endpoint of interest was all-cause mortality. RESULTS: Among 552 patients, median baseline GNRI was 109 (IQR: 101-116); 94 (17.0%) had malnutrition. All-cause mortality at 4 years was greater in patients with vs those without malnutrition (68.3% vs 52.8%; P = 0.001). Using multivariable analysis, both baseline malnutrition (adjusted-HR [adj-HR]: 1.37; 95% CI: 1.03-1.82; P = 0.03) and randomization to TEER plus GDMT compared with GDMT alone (adj-HR: 0.65; 95% CI: 0.51-0.82; P = 0.0003) were independent predictors of 4-year mortality. In contrast, GNRI was unrelated to the 4-year rate of heart failure hospitalization (HFH), although TEER treatment reduced HFH (adj-HR: 0.46; 95% CI: 0.36-0.56). The reductions in death (adj-Pinteraction = 0.46) and HFH (adj-Pinteraction = 0.67) with TEER were consistent in patients with and without malnutrition. CONCLUSIONS: Malnutrition was present in 1 of 6 patients with HF and severe SMR enrolled in COAPT and was independently associated with increased 4-year mortality (but not HFH). TEER reduced mortality and HFH in patients with and without malnutrition. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] and COAPT CAS [COAPT]; NCT01626079).

Rationale and design of a randomized study comparing the Watchman FLX device to DOACs in patients with atrial fibrillation.

BACKGROUND: Percutaneous left atrial appendage (LAA) closure (LAAC) was developed as a nonpharmacologic alternative to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) who are at an increased risk for stroke or systemic embolism. The Watchman device permanently seals off the LAA to prevent thrombi from escaping into the circulation. Previous randomized trials have established the safety and efficacy of LAAC compared to warfarin. However, direct OACs (DOACs) have become the preferred pharmacologic strategy for stroke prevention in patients with AF, and there is limited data comparing Watchman FLX to DOACs in a broad AF patient population. CHAMPION-AF is designed to prospectively determine whether LAAC with Watchman FLX is a reasonable first-line alternative to DOACs in patients with AF who are indicated for OAC therapy. STUDY DESIGN: A total of 3,000 patients with a CHA2DS2-VASc score ≥2 (men) or ≥3 (women) were randomized to Watchman FLX or DOAC in a 1:1 allocation at 142 global clinical sites. Patients in the device arm were to be treated with DOAC and aspirin, DOAC alone, or DAPT for at least 3 months postimplant followed by aspirin or P2Y12 inhibitor for 1-year. Control patients were required to take an approved DOAC for the duration of the trial. Clinical follow-up visits are scheduled at 3- and 12-months, and then annually through 5 years; LAA imaging is required at 4 months in the device group. Two primary end points will be evaluated at 3 years: (1) composite of stroke (ischemic/hemorrhagic), cardiovascular death, and systemic embolism compared for noninferiority, and (2) nonprocedural bleeding (International Society on Thrombosis and Haemostasis [ISTH] major and clinically relevant nonmajor bleeding) tested for superiority in the device arm against DOACs. The third primary noninferiority end point is the composite of ischemic stroke and systemic embolism at 5 years. Secondary end points include 3- and 5-year rates of (1) ISTH-defined major bleeding and (2) the composite of cardiovascular death, all stroke, systemic embolism, and nonprocedural ISTH bleeding. CONCLUSIONS: This study will prospectively evaluate whether LAAC with the Watchman FLX device is a reasonable alternative to DOACs in patients with AF. CLINICAL TRIAL REGISTRATION: NCT04394546.

Cerebrovascular Events After Transcatheter Edge-to-Edge Repair and Guideline-Directed Medical Therapy in the COAPT Trial.

BACKGROUND: Little is known regarding the risk of cerebrovascular events (CVE) in patients with heart failure and severe secondary mitral regurgitation treated with transcatheter edge-to-edge repair (TEER). OBJECTIVES: The study sought to examine the incidence, predictors, timing, and prognostic impact of CVE (stroke or transient ischemic attack) in the COAPT (Cardiovascular Outcomes Assessment of the Mitraclip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial. METHODS: A total of 614 patients with heart failure and severe secondary mitral regurgitation were randomized to TEER plus guideline-directed medical therapy (GDMT) vs GDMT alone. RESULTS: At 4-year follow-up, 50 CVEs occurred in 48 (7.8%) of the 614 total patients enrolled in the COAPT trial; Kaplan-Meier event rates were 12.3% in the TEER group and 10.2 in the GDMT alone group (P = 0.91). Within 30 days of randomization, CVE occurred in 2 (0.7%) patients randomized to TEER and 0% randomized to GDMT (P = 0.15). Baseline renal dysfunction and diabetes were independently associated with increased risk of CVE, while baseline anticoagulation was associated with a reduction of CVE. A significant interaction was present between treatment group and anticoagulation such that TEER compared with GDMT alone was associated with a reduced risk of CVE among patients with anticoagulation (adjusted HR: 0.24; 95% CI: 0.08-0.73) compared with an increased risk of CVE in patients without anticoagulation (adjusted HR: 2.27; 95% CI: 1.08-4.81; Pinteraction = 0.001). CVE was an independent predictor of death within 30 days after the event (HR: 14.37; 95% CI: 7.61, 27.14; P < 0.0001). CONCLUSIONS: In the COAPT trial, the 4-year rate of CVE was similar after TEER or GDMT alone. CVE was strongly associated with mortality. Whether anticoagulation is effective at reducing CVE risk after TEER warrants further study. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] and COAPT CAS [COAPT); NCT01626079).

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.

Transcatheter Mitral Valve Replacement Versus Medical Therapy for Secondary Mitral Regurgitation: A Propensity Score-Matched Comparison.

BACKGROUND: Transcatheter mitral valve replacement (TMVR) is an emerging therapeutic alternative for patients with secondary mitral regurgitation (MR). Outcomes of TMVR versus guideline-directed medical therapy (GDMT) have not been investigated for this population. This study aimed to compare clinical outcomes of patients with secondary MR undergoing TMVR versus GDMT alone. METHODS: The CHOICE-MI registry (Choice of Optimal Transcatheter Treatment for Mitral Insufficiency) included patients with MR undergoing TMVR using dedicated devices. Patients with MR pathogeneses other than secondary MR were excluded. Patients treated with GDMT alone were derived from the control arm of the COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation). We compared outcomes between the TMVR and GDMT groups, using propensity score matching to adjust for baseline differences. RESULTS: After propensity score matching, 97 patient pairs undergoing TMVR (72.9±8.7 years; 60.8% men; transapical access, 91.8%) versus GDMT (73.1±11.0 years; 59.8% men) were compared. At 1 and 2 years, residual MR was ≤1+ in all patients of the TMVR group compared with 6.9% and 7.7%, respectively, in those receiving GDMT alone (both P<0.001). The 2-year rate of heart failure hospitalization was significantly lower in the TMVR group (32.8% versus 54.4%; hazard ratio, 0.59 [95% CI, 0.35-0.99]; P=0.04). Among survivors, a higher proportion of patients were in the New York Heart Association functional class I or II in the TMVR group at 1 year (78.2% versus 59.7%; P=0.03) and at 2 years (77.8% versus 53.2%; P=0.09). Two-year mortality was similar in the 2 groups (TMVR versus GDMT, 36.8% versus 40.8%; hazard ratio, 1.01 [95% CI, 0.62-1.64]; P=0.98). CONCLUSIONS: In this observational comparison, over 2-year follow-up, TMVR using mostly transapical devices in patients with secondary MR was associated with significant reduction of MR, symptomatic improvement, less frequent hospitalizations for heart failure, and similar mortality compared with GDMT. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT04688190 (CHOICE-MI) and NCT01626079 (COAPT).

Transcatheter Repair for Patients with Tricuspid Regurgitation.

BACKGROUND: Severe tricuspid regurgitation is a debilitating condition that is associated with substantial morbidity and often with poor quality of life. Decreasing tricuspid regurgitation may reduce symptoms and improve clinical outcomes in patients with this disease. METHODS: We conducted a prospective randomized trial of percutaneous tricuspid transcatheter edge-to-edge repair (TEER) for severe tricuspid regurgitation. Patients with symptomatic severe tricuspid regurgitation were enrolled at 65 centers in the United States, Canada, and Europe and were randomly assigned in a 1:1 ratio to receive either TEER or medical therapy (control). The primary end point was a hierarchical composite that included death from any cause or tricuspid-valve surgery; hospitalization for heart failure; and an improvement in quality of life as measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ), with an improvement defined as an increase of at least 15 points in the KCCQ score (range, 0 to 100, with higher scores indicating better quality of life) at the 1-year follow-up. The severity of tricuspid regurgitation and safety were also assessed. RESULTS: A total of 350 patients were enrolled; 175 were assigned to each group. The mean age of the patients was 78 years, and 54.9% were women. The results for the primary end point favored the TEER group (win ratio, 1.48; 95% confidence interval, 1.06 to 2.13; P = 0.02). The incidence of death or tricuspid-valve surgery and the rate of hospitalization for heart failure did not appear to differ between the groups. The KCCQ quality-of-life score changed by a mean (±SD) of 12.3±1.8 points in the TEER group, as compared with 0.6±1.8 points in the control group (P<0.001). At 30 days, 87.0% of the patients in the TEER group and 4.8% of those in the control group had tricuspid regurgitation of no greater than moderate severity (P<0.001). TEER was found to be safe; 98.3% of the patients who underwent the procedure were free from major adverse events at 30 days. CONCLUSIONS: Tricuspid TEER was safe for patients with severe tricuspid regurgitation, reduced the severity of tricuspid regurgitation, and was associated with an improvement in quality of life. (Funded by Abbott; TRILUMINATE Pivotal ClinicalTrials.gov number, NCT03904147.).