Outcomes and feasibility of redo-TAVR after Sapien 3 Ultra TAVR in extremely-undersized versus nominally-sized annuli.

OBJECTIVES: To compare outcomes in Sapien 3 Ultra (S3U) transcatheter aortic valve replacement (TAVR) with extreme annular undersizing (EAU) versus nominal annular sizing (NAS). BACKGROUND: The Edwards S3U valve has reduced paravalvular leak (PVL) in TAVR but outcomes remain unknown in extremely undersized anatomy. Implanting a smaller S3U valve may facilitate future redo-TAVR but risk compromising hemodynamics. METHODS: From December 2019 to July 2021, 366 patients with native aortic stenosis underwent S3U TAVR. Patients with EAU (annular areas >430 mm2 for 23 mm or >546 mm2 for 26 mm) were compared to NAS (338-430 mm2 for 23 mm or 430-546 mm2 for 26 mm). In-hospital and 30-day outcomes, and redo-TAVR feasibility were determined. RESULTS: There were 79 (21.6%) EAU patients, with more bicuspid (p = 0.0014) and ≥moderate annular/left ventricular outflow tract calcification (p < 0.001). The EAU group had less annular oversizing than NAS group (23 mm: -8.2 ± 2.6% vs. 4.0 ± 7.0%, p < 0.001; 26 mm: -8.9 ± 2.2% vs. 6.7 ± 6.9%, p < 0.001), more balloon overfilling (71.3% vs. 11.6%, p < 0.001), and postdilatation (15.0% vs. 5.8%, p = 0.016). No differences were found in in-hospital or 30-day mortality and stroke (p > 0.05). Mild PVL (13.4% EAU vs. 11.5% NAS, p = 0.56) and mean gradients (23 mm: 13.0 ± 4.5 vs. 14.1 ± 5.4 mmHg, p = 0.40; 26 mm: 11.4 ± 4.1 vs. 11.5 ± 3.9 mmHg, p = 1.0) were similar at 30 days. Had the EAU group undergone NAS with the larger Sapien 3/S3U, by computed tomography analysis simulating 80:20 or 90:10 target implant depth, 33.3%-60.9% (vs. 4.3%-23.2%) would not be feasible for redo-TAVR due to high risk of coronary obstruction. CONCLUSIONS: In this first report of EAU with S3U TAVR, similar excellent short-term outcomes can be achieved compared to NAS, and may preserve future redo-TAVR option.

Impact of transcatheter heart valve type on outcomes of surgical explantation after failed transcatheter aortic valve replacement: the EXPLANT-TAVR international registry.

BACKGROUND: There are limited data on the impact of transcatheter heart valve (THV) type on the outcomes of surgical explantation after THV failure. AIMS: We sought to determine the outcomes of transcatheter aortic valve replacement (TAVR) explantation for failed balloon-expandable valves (BEV) versus self-expanding valves (SEV). METHODS: From November 2009 to February 2022, 401 patients across 42 centres in the EXPLANT-TAVR registry underwent TAVR explantation during a separate admission from the initial TAVR. Mechanically expandable valves (N=10, 2.5%) were excluded. The outcomes of TAVR explantation were compared for 202 (51.7%) failed BEV and 189 (48.3%) failed SEV. RESULTS: Among 391 patients analysed (mean age: 73.0±9.8 years; 33.8% female), the median time from index TAVR to TAVR explantation was 13.3 months (interquartile range 5.1-34.8), with no differences between groups. Indications for TAVR explantation included endocarditis (36.0% failed SEV vs 55.4% failed BEV; p<0.001), paravalvular leak (21.2% vs 11.9%; p=0.014), structural valve deterioration (30.2% vs 21.8%; p=0.065) and prosthesis-patient mismatch (8.5% vs 10.4%; p=0.61). The SEV group trended fewer urgent/emergency surgeries (52.0% vs 62.3%; p=0.057) and more root replacement (15.3% vs 7.4%; p=0.016). Concomitant cardiac procedures were performed in 57.8% of patients, including coronary artery bypass graft (24.8%), and mitral (38.9%) and tricuspid (14.6%) valve surgery, with no differences between groups. In-hospital, 30-day, and 1-year mortality and stroke rates were similar between groups (allp>0.05), with no differences in cumulative mortality at 3 years (log-rank p=0.95). On multivariable analysis, concomitant mitral surgery was an independent predictor of 1-year mortality after BEV explant (hazard ratio [HR] 2.00, 95% confidence interval [CI]: 1.07-3.72) and SEV explant (HR 2.00, 95% CI: 1.08-3.69). CONCLUSIONS: In the EXPLANT-TAVR global registry, BEV and SEV groups had different indications for surgical explantation, with more root replacements in SEV failure, but no differences in midterm mortality and morbidities. Further refinement of TAVR explantation techniques are important to improving outcomes.

Calpain inhibition preserves talin and attenuates right heart failure in acute pulmonary hypertension.

Right heart failure from right ventricular (RV) pressure overload is a major cause of morbidity and mortality, but its mechanism is incompletely understood. We tested the hypothesis that right heart failure during 4 hours of RV pressure overload is associated with alterations of the focal adhesion protein talin, and that the inhibition of calpain attenuates RV dysfunction and preserves RV talin. Anesthetized open-chest pigs treated with the calpain inhibitor MDL-28170 (n = 20) or inactive vehicle (n = 23) underwent 4 hours of RV pressure overload by pulmonary artery constriction (initial RV systolic pressure, 64 ± 1 and 66 ± 1 mm Hg in MDL-28170 and vehicle-treated pigs, respectively). Progressive RV contractile dysfunction was attenuated by MDL-28170: after 4 hours of RV pressure overload, RV systolic pressure was 44 ± 4 mm Hg versus 49 ± 6 mm Hg (P = 0.011), and RV stroke work was 72 ± 5% of baseline versus 90 ± 5% of baseline, (P = 0.027), in vehicle-treated versus MDL-28170-treated pigs, respectively. MDL-28170 reduced the incidence of hemodynamic instability (death or systolic blood pressure of < 85 mm Hg) by 46% (P = 0.013). RV pressure overload disrupted talin organization. MDL-28170 preserved talin abundance in the RV free wall (P = 0.039), and talin abundance correlated with the maintenance of RV free wall stroke work (r = 0.58, P = 0.0039). α-actinin and vinculin showed similar changes according to immunohistology. Right heart failure from acute RV pressure overload is associated with reduced talin abundance and disrupted talin organization. Calpain inhibition preserves the abundance and organization of talin and RV function. Calpain inhibition may offer clinical utility in treating acute cor pulmonale.

Use of antiplatelet therapy after percutaneous coronary intervention with bare-metal stents and different types of drug-eluting stents.

Dual antiplatelet therapy (DAPT) with a thienopyridine and aspirin has been the standard of care post coronary stent implantation. DAPT has been shown to reduce the risk of stent thrombosis (ST) and complications of myocardial infarction and death after placement of a drug-eluting stent (DES) and bare-metal stent (BMS). This article reviews the available clinical efficacy and safety data of antiplatelet therapies. The aim of this review is to highlight not only the importance of antiplatelets in the prevention of early and late thrombosis but also emphasize the importance of newer more potent antiplatelet agents and their role in the setting of clopidogrel resistance. MEDLINE, and EMBASE were searched for studies related to the clinical efficacy and safety of antiplatelet therapy after DES and BMS placement using the terms dual antiplatelet therapy, thienopyridine, aspirin, clopidogrel, prasugrel, ticagrelor,elinogrel, bare-metal stents, drug-eluting stent, stent thrombosis and myocardial infarction.