Predictors of Cerebral Embolic Debris During Transcatheter Aortic Valve Replacement: The SafePass 2 First-in-Human Study.

Transcatheter aortic valve replacement (TAVR) generates significant debris, and strategies to mitigate cerebral embolization are needed. The novel Emboliner embolic protection catheter (Emboline, Inc., Santa Cruz, California) is designed to capture all particles generated during TAVR. This first-in-human study sought to assess the safety and feasibility of the device and to characterize the distribution and histopathology of the debris generated during TAVR. The SafePass 2 study was a prospective, nonrandomized, multicenter, single-arm investigation of the Emboliner device. Primary end points included 30-day major adverse cardiac and cerebrovascular events (MACCE) and technical performance. Computed tomography angiography was analyzed by an independent core laboratory, and filters were sent for histopathology of captured debris. Predictors of particle number were identified using >150 µm and >500 µm size thresholds. Of 31 subjects enrolled, technical success was 100%, and 30-day MACCE was 6.5% (2 cerebrovascular accidents, with 1 attributed to subtherapeutic dosing of rivaroxaban along with atrial fibrillation and the other to possible previous small ischemic strokes on magnetic resonance imaging; neither MACCE event had a causal relation to the Emboliner). All filters contained debris, with a median of 191.0 particles >150 µm and 14.0 particles >500 µm. Histopathology revealed mostly acute thrombus and valve or arterial tissue with lesser amounts of calcified tissue. A history of atrial fibrillation predicted a greater number of particles >500 µm (p = 0.0259) and its presence on admission was associated with 4.1 times more particles >150 µm (p = 0.0130) and 8.1 times more particles >500 µm (p = 0.0086). Self-expanding valves were associated with twice the number of particles >150 µm (p = 0.0281). TASK score was positively correlated with number of particles >500 µm (p = 0.0337). The Emboliner device was safe and feasible. Emboli after TAVR appear more numerous than previously documented. Atrial fibrillation, higher TASK score, and self-expanding valve use conferred higher embolic burden. Notably, none of the tested computed tomography angiography features were able to identify with higher embolic risk. Larger-scale studies are needed to identify high-risk patients for selective embolic protection device use.

Transcatheter Tricuspid Valve Intervention in Patients With Right Ventricular Dysfunction or Pulmonary Hypertension: Insights From the TriValve Registry.

BACKGROUND: Scarce data exist on patients with right ventricular dysfunction (RVD) or pulmonary hypertension (PH) undergoing transcatheter tricuspid valve intervention. This study aimed to determine the early and midterm outcomes and the factors associated with mortality in this group of patients. METHODS: This subanalysis of the multicenter TriValve (Transcatheter Tricuspid Valve Therapies) registry included 300 patients with severe tricuspid regurgitation with RVD (n=244), PH (n=127), or both (n=71) undergoing transcatheter tricuspid valve intervention. RVD was defined as a tricuspid annular plane systolic excursion <17 mm, and PH as an estimated pulmonary artery systolic pressure ≥50 mm Hg. RESULTS: Mean age of the patients was 77±9 years (54% women). Procedural success was 80.7%, and 9 patients (3%) died during the hospitalization. At a median follow-up of 6 (interquartile range, 2-12) months, 54 patients (18%) died, and the independent associated factors were higher gamma-glutamyl transferase values at baseline (hazard ratio, 1.02 for each increase of 10 u/L [95% CI, 1.002-1.04]), poorer renal function defined as an estimated glomerular filtration rate <45 mL/min (hazard ratio, 2.3 [95% CI, 1.22-4.33]), and the lack of procedural success (hazard ratio, 2.11 [95% CI, 1.17-3.81]). The grade of RVD and the amount of PH at baseline were not found to be predictors of mortality. Most patients alive at follow-up improved their functional class (New York Heart Association I-II in 66% versus 7% at baseline, P<0.001). CONCLUSIONS: In patients with severe tricuspid regurgitation and RVD/PH, transcatheter tricuspid valve intervention was associated with high procedural success and a relatively low in-hospital mortality, along with significant improvements in functional status. However, about 1 out of 5 patients died after a median follow-up of 6 months, with hepatic congestion, renal dysfunction, and the lack of procedural success determining an increased risk. These results may improve the clinical evaluation of transcatheter tricuspid valve intervention candidates and would suggest a closer follow-up in those at increased risk. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03416166.

Impact of Massive or Torrential Tricuspid Regurgitation in Patients Undergoing Transcatheter Tricuspid Valve Intervention.

OBJECTIVES: The aim of this study was to assess the clinical outcome of baseline massive or torrential tricuspid regurgitation (TR) after transcatheter tricuspid valve intervention (TTVI). BACKGROUND: The use of TTVI to treat symptomatic severe TR has been increasing rapidly, but little is known regarding the impact of massive or torrential TR beyond severe TR. METHODS: The study population comprised 333 patients with significant symptomatic TR from the TriValve Registry who underwent TTVI. Mid-term outcomes after TTVI were assessed according to the presence of massive or torrential TR, defined as vena contracta width ≥14 mm. Procedural success was defined as patient survival after successful device implantation and delivery system retrieval, with residual TR ≤2+. The primary endpoint comprised survival rate and freedom from rehospitalization for heart failure, survival rate, and rehospitalization at 1 year. RESULTS: Baseline massive or torrential TR and severe TR were observed in 154 patients (46.2%) and 179 patients (53.8%), respectively. Patients with massive or torrential TR had a higher prevalence of ascites than those with severe TR (27.3% vs. 20.4%, respectively; p = 0.15) and demonstrated a similar procedural success rate (83.2% vs. 77.3%, respectively; p = 0.21). The incidence of peri-procedural adverse events was low, with no significant between-group differences. Freedom from the composite endpoint was significantly lower in patients with massive or torrential TR than in those with severe TR, which was significantly associated with an increased risk for 1-year death of any cause or rehospitalization for heart failure (adjusted hazard ratio: 1.91; 95% confidence interval: 1.10 to 3.34; p = 0.022). Freedom from the composite endpoint was significantly higher in patients with massive or torrential TR when procedural success was achieved (69.9% vs. 54.2%, p = 0.048). CONCLUSIONS: Baseline massive or torrential TR is associated with an increased risk for all-cause mortality and rehospitalization for heart failure 1 year after TTVI. Procedural success is related to better outcomes, even in the presence of baseline massive or torrential TR. (International Multisite Transcatheter Tricuspid Valve Therapies Registry [TriValve]; NCT03416166).

Outcomes of TTVI in Patients With Pacemaker or Defibrillator Leads: Data From the TriValve Registry.

OBJECTIVES: The interference of a transtricuspid cardiac implantable electronic device (CIED) lead with tricuspid valve function may contribute to the mechanism of tricuspid regurgitation (TR) and poses specific therapeutic challenges during transcatheter tricuspid valve intervention (TTVI). Feasibility and efficacy of TTVI in presence of a CIED is unclear. BACKGROUND: Feasibility of TTVI in presence of a CIED lead has never been proven on a large basis. METHODS: The study population consisted of 470 patients with severe symptomatic TR from the TriValve (Transcatheter Tricuspid Valve Therapies) registry who underwent TTVI at 21 centers between 2015 and 2018. The association of CIED and outcomes were assessed. RESULTS: Pre-procedural CIED was present in 121 of 470 (25.7%) patients. The most frequent location of the CIED lead was the posteroseptal commissure (44.0%). As compared with patients without a transvalvular lead (no-CIED group), patients having a tricuspid lead (CIED group) were more symptomatic (New York Heart Association functional class III to IV in 95.9% vs. 92.3%; p = 0.02) and more frequently had previous episodes of right heart failure (87.8% vs. 69.0%; p = 0.002). No-CIED patients had more severe TR (effective regurgitant orifice area 0.7 ± 0.6 cm2 vs. 0.6 ± 0.3 cm2; p = 0.02), but significantly better right ventricular function (tricuspid annular plane systolic excursion = 16.7 ± 5.0 mm vs. 15.9 ± 4.0 mm; p = 0.04). Overall, 373 patients (79%) were treated with the MitraClip (Abbott Vascular, Santa Clara, California) (106 [87.0%] in the CIED group). Among them, 154 (33%) patients had concomitant transcatheter mitral repair (55 [46.0%] in the CIED group, all MitraClip). Procedural success was achieved in 80.0% of no-CIED patients and in 78.6% of CIED patients (p = 0.74), with an in-hospital mortality of 2.9% and 3.7%, respectively (p = 0.70). At 30 days, residual TR ≤2+ was observed in 70.8% of no-CIED and in 73.7% of CIED patients (p = 0.6). Symptomatic improvement was observed in both groups (NYHA functional class I to II at 30 days: 66.0% vs. 65.0%; p = 0.30). Survival at 12 months was 80.7 ± 3.0% in the no-CIED patients and 73.6 ± 5.0% in the CIED patients (p = 0.30). CONCLUSIONS: TTVI is feasible in selected patients with CIED leads and acute procedural success and short-term clinical outcomes are comparable to those observed in patients without a transtricuspid lead.

Transcatheter Versus Medical Treatment of Patients With Symptomatic Severe Tricuspid Regurgitation.

BACKGROUND: Tricuspid regurgitation is associated with increased rates of heart failure (HF) and mortality. Transcatheter tricuspid valve interventions (TTVI) are promising, but the clinical benefit is unknown. OBJECTIVES: The purpose of this study was to investigate the potential benefit of TTVI over medical therapy in a propensity score matched population. METHODS: The TriValve (Transcatheter Tricuspid Valve Therapies) registry collected 472 patients from 22 European and North American centers who underwent TTVI from 2016 to 2018. A control cohort formed by 2 large retrospective registries enrolling medically managed patients with ≥ moderate tricuspid regurgitation in Europe and North America (n = 1,179) were propensity score 1:1 matched (distance ± 0.2 SD) using age, EuroSCORE II, and systolic pulmonary artery pressure. Survival was tested with Cox regression analysis. Primary endpoint was 1-year mortality or HF rehospitalization or the composite. RESULTS: After matching, 268 adequately matched pairs of patients were identified. Compared with control subjects, TTVI patients had lower 1-year mortality (23 ± 3% vs. 36 ± 3%; p = 0.001), rehospitalization (26 ± 3% vs. 47 ± 3%; p < 0.0001), and composite endpoint (32 ± 4% vs. 49 ± 3%; p = 0.0003). TTVI was associated with greater survival and freedom from HF rehospitalization (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.46 to 0.79; p = 0.003 unadjusted), which remained significant after adjusting for sex, New York Heart Association functional class, right ventricular dysfunction, and atrial fibrillation (HR: 0.39; 95% CI: 0.26 to 0.59; p < 0.0001) and after further adjustment for mitral regurgitation and pacemaker/defibrillator (HR: 0.35; 95% CI: 0.23 to 0.54; p < 0.0001). CONCLUSIONS: In this propensity-matched case-control study, TTVI is associated with greater survival and reduced HF rehospitalization compared with medical therapy alone. Randomized trials should be performed to confirm these results.

Outcomes After Current Transcatheter Tricuspid Valve Intervention: Mid-Term Results From the International TriValve Registry.

OBJECTIVES: A large, prospective international registry was developed to evaluate the initial clinical applications of transcatheter tricuspid valve intervention (TTVI) with different devices. BACKGROUND: TTVI for native tricuspid valve dysfunction has been emerging during the last few years as an alternative therapeutic option to serve a large high-risk population of patients with severe symptomatic tricuspid regurgitation (TR). METHODS: The TriValve Registry included 312 high-risk patients with severe TR (76.4 ± 8.5 years of age; 57% female; EuroSCORE II 9 ± 8%) at 18 centers. Interventions included repair at the level of the leaflets (MitraClip, Abbott Vascular, Santa Clara, California; PASCAL Edwards Lifesciences, Irvine, California), annulus (Cardioband, Edwards Lifesciences; TriCinch, 4tech, Galway, Ireland; Trialign, Mitraling, Tewksbury, Massachusetts), or coaptation (FORMA, Edwards Lifesciences) and replacement (Caval Implants, NaviGate, NaviGate Cardiac Structures, Lake Forest, California). Clinical outcomes were prospectively determined during mid-term follow-up. RESULTS: A total of 108 patients (34.6%) had prior left heart valve intervention (84 surgical and 24 transcatheter, respectively). TR etiology was functional in 93%, and mean annular diameter was 46.9 ± 9 mm. In 75% of patients the regurgitant jet was central (vena contracta 1.1 ± 0.5; effective regurgitant orifice area 0.78 ± 0.6 cm2). Pre-procedural systolic pulmonary artery pressure was 41 ± 14.8 mm Hg. Implanted devices included: MitraClip in 210 cases, Trialign in 18 cases, TriCinch first generation in 14 cases, caval valve implantation in 30 cases, FORMA in 24 cases, Cardioband in 13 cases, NaviGate in 6 cases, and PASCAL in 1. In 64% of the cases, TTVI was performed as a stand-alone procedure. Procedural success (defined as the device successfully implanted and residual TR ≤2+) was 72.8%. Greater coaptation depth (odds ratio: 24.1; p = 0.002) was an independent predictor of reduced device success. Thirty-day mortality was 3.6% and was significantly lower among patients with procedural success (1.9% vs. 6.9%; p = 0.04); Actuarial survival at 1.5 years was 82.8 ± 4% and was significantly higher among patients who had procedural success achieved. CONCLUSIONS: TTVI is feasible with different technologies, has a reasonable overall procedural success rate, and is associated with low mortality and significant clinical improvement. Mid-term survival is favorable in this high-risk population. Greater coaptation depth is associated with reduced procedural success, which is an independent predictor of mortality.