Diverse roles of pontine NPS-expressing neurons in sleep regulation.

Neuropeptide S (NPS) was postulated to be a wake-promoting neuropeptide with unknown mechanism, and a mutation in its receptor (NPSR1) causes the short sleep duration trait in humans. We investigated the role of different NPS+ nuclei in sleep/wake regulation. Loss-of-function and chemogenetic studies revealed that NPS+ neurons in the parabrachial nucleus (PB) are wake-promoting, whereas peri-locus coeruleus (peri-LC) NPS+ neurons are not important for sleep/wake modulation. Further, we found that a NPS+ nucleus in the central gray of the pons (CGPn) strongly promotes sleep. Fiber photometry recordings showed that NPS+ neurons are wake-active in the CGPn and wake/REM-sleep active in the PB and peri-LC. Blocking NPS-NPSR1 signaling or knockdown of Nps supported the function of the NPS-NPSR1 pathway in sleep/wake regulation. Together, these results reveal that NPS and NPS+ neurons play dichotomous roles in sleep/wake regulation at both the molecular and circuit levels.

Transcatheter Aortic-Valve Replacement in Low-Risk Patients at Five Years.

BACKGROUND: A previous analysis in this trial showed that among patients with severe, symptomatic aortic stenosis who were at low surgical risk, the rate of the composite end point of death, stroke, or rehospitalization at 1 year was significantly lower with transcatheter aortic-valve replacement (TAVR) than with surgical aortic-valve replacement. Longer-term outcomes are unknown. METHODS: We randomly assigned patients with severe, symptomatic aortic stenosis and low surgical risk to undergo either TAVR or surgery. The first primary end point was a composite of death, stroke, or rehospitalization related to the valve, the procedure, or heart failure. The second primary end point was a hierarchical composite that included death, disabling stroke, nondisabling stroke, and the number of rehospitalization days, analyzed with the use of a win ratio analysis. Clinical, echocardiographic, and health-status outcomes were assessed through 5 years. RESULTS: A total of 1000 patients underwent randomization: 503 patients were assigned to undergo TAVR, and 497 to undergo surgery. A component of the first primary end point occurred in 111 of 496 patients in the TAVR group and in 117 of 454 patients in the surgery group (Kaplan-Meier estimates, 22.8% in the TAVR group and 27.2% in the surgery group; difference, -4.3 percentage points; 95% confidence interval [CI], -9.9 to 1.3; P = 0.07). The win ratio for the second primary end point was 1.17 (95% CI, 0.90 to 1.51; P = 0.25). The Kaplan-Meier estimates for the components of the first primary end point were as follows: death, 10.0% in the TAVR group and 8.2% in the surgery group; stroke, 5.8% and 6.4%, respectively; and rehospitalization, 13.7% and 17.4%. The hemodynamic performance of the valve, assessed according to the mean (±SD) valve gradient, was 12.8±6.5 mm Hg in the TAVR group and 11.7±5.6 mm Hg in the surgery group. Bioprosthetic-valve failure occurred in 3.3% of the patients in the TAVR group and in 3.8% of those in the surgery group. CONCLUSIONS: Among low-risk patients with severe, symptomatic aortic stenosis who underwent TAVR or surgery, there was no significant between-group difference in the two primary composite outcomes. (Funded by Edwards Lifesciences; PARTNER 3 ClinicalTrials.gov number, NCT02675114.).

An excitatory peri-tegmental reticular nucleus circuit for wake maintenance.

Sleep is a necessity for our survival, but its regulation remains incompletely understood. Here, we used a human sleep duration gene to identify a population of cells in the peri-tegmental reticular nucleus (pTRNADRB1) that regulate sleep-wake, uncovering a role for a poorly understood brain area. Although initial ablation in mice led to increased wakefulness, further validation revealed that pTRNADRB1 neuron stimulation strongly promotes wakefulness, even after stimulation offset. Using combinatorial genetics, we found that excitatory pTRNADRB1 neurons promote wakefulness. pTRN neurons can be characterized as anterior- or posterior-projecting neurons based on multiplexed analysis of projections by sequencing (MAPseq) analysis. Finally, we found that pTRNADRB1 neurons promote wakefulness, in part, through projections to the lateral hypothalamus. Thus, human genetic information from a human sleep trait allowed us to identify a role for the pTRN in sleep-wake regulation.

TRI-SCORE and benefit of intervention in patients with severe tricuspid regurgitation.

BACKGROUND AND AIMS: Benefit of tricuspid regurgitation (TR) correction and timing of intervention are unclear. This study aimed to compare survival rates after surgical or transcatheter intervention to conservative management according to a TR clinical stage as assessed using the TRI-SCORE. METHODS: A total of 2,413 patients with severe isolated functional TR were enrolled in TRIGISTRY (1217 conservatively managed, 551 isolated tricuspid valve surgery, and 645 transcatheter valve repair). The primary endpoint was survival at 2 years. RESULTS: The TRI-SCORE was low (≤3) in 32%, intermediate (4-5) in 33%, and high (≥6) in 35%. A successful correction was achieved in 97% and 65% of patients in the surgical and transcatheter groups, respectively. Survival rates decreased with the TRI-SCORE in the three treatment groups (all P < .0001). In the low TRI-SCORE category, survival rates were higher in the surgical and transcatheter groups than in the conservative management group (93%, 87%, and 79%, respectively, P = .0002). In the intermediate category, no significant difference between groups was observed overall (80%, 71%, and 71%, respectively, P = .13) but benefit of the intervention became significant when the analysis was restricted to patients with successful correction (80%, 81%, and 71%, respectively, P = .009). In the high TRI-SCORE category, survival was not different to conservative management in the surgical and successful repair group (61% and 68% vs 58%, P = .26 and P = .18 respectively). CONCLUSIONS: Survival progressively decreased with the TRI-SCORE irrespective of treatment modality. Compared to conservative management, an early and successful surgical or transcatheter intervention improved 2-year survival in patients at low and, to a lower extent, intermediate TRI-SCORE, while no benefit was observed in the high TRI-SCORE category.

Economic Outcomes of Transcatheter Versus Surgical Aortic Valve Replacement in Patients with Severe Aortic Stenosis and Low Surgical Risk: Results from the PARTNER 3 Trial.

BACKGROUND: In patients with severe symptomatic aortic stenosis at low surgical risk, transfemoral transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve has been shown to reduce the composite of death, stroke, or rehospitalization at 2-year follow-up compared with surgical aortic valve replacement (SAVR). Whether TAVR is cost-effective compared with SAVR for low-risk patients remains uncertain. METHODS: Between 2016 and 2017, 1000 low-risk patients with aortic stenosis were randomly assigned to TAVR with the SAPIEN 3 valve or SAVR in the PARTNER 3 trial (Placement of Aortic Transcatheter Valves). Of these patients, 929 underwent valve replacement, were enrolled in the United States, and were included in the economic substudy. Procedural costs were estimated using measured resource use. Other costs were determined by linkage with Medicare claims or by regression models when linkage was not feasible. Health utilities were estimated using the EuroQOL 5-item questionnaire. With the use of a Markov model informed by in-trial data, lifetime cost-effectiveness from the perspective of the US health care system was estimated in terms of cost per quality-adjusted life-year gained. RESULTS: Although procedural costs were nearly $19 000 higher with TAVR, total index hospitalization costs were only $591 more with TAVR compared with SAVR. Follow-up costs were lower with TAVR such that TAVR led to 2-year cost savings of $2030/patient compared with SAVR (95% CI, -$6222 to $1816) and a gain of 0.05 quality-adjusted life-years (95% CI, -0.003 to 0.102). In our base-case analysis, TAVR was projected to be an economically dominant strategy with a 95% probability that the incremental cost-effectiveness ratio for TAVR would be <$50 000/quality-adjusted life-year gained (consistent with high economic value from a US health care perspective). These findings were sensitive to differences in long-term survival, however, such that a modest long-term survival advantage with SAVR would render SAVR cost-effective (although not cost saving) compared with TAVR. CONCLUSIONS: For patients with severe aortic stenosis and low surgical risk similar to those enrolled in the PARTNER 3 trial, transfemoral TAVR with the SAPIEN 3 valve is cost saving compared with SAVR at 2 years and is projected to be economically attractive in the long run as long as there are no substantial differences in late death between the 2 strategies. Long-term follow-up will be critical to ultimately determine the preferred treatment strategy for low-risk patients from both a clinical and economic perspective.

Treatment of late paravalvular regurgitation after transcatheter aortic valve implantation: prognostic implications.

AIMS: Paravalvular regurgitation (PVR) after transcatheter aortic valve implantation (TAVI) is associated with increased morbidity and mortality. The effect of transcatheter interventions to treat PVR after the index TAVI was investigated. METHODS AND RESULTS: A registry of consecutive patients who underwent transcatheter intervention for ≥ moderate PVR after the index TAVI at 22 centers. The principal outcomes were residual aortic regurgitation (AR) and mortality at 1 year after PVR treatment. A total of 201 patients were identified: 87 (43%) underwent redo-TAVI, 79 (39%) plug closure, and 35 (18%) balloon valvuloplasty. Median TAVI-to-re-intervention time was 207 (35; 765) days. The failed valve was self-expanding in 129 (63.9%) patients. The most frequent devices utilized were a Sapien 3 valve for redo-TAVI (55, 64%), an AVP II as plug (33, 42%), and a True balloon for valvuloplasty (20, 56%). At 30 days, AR ≥ moderate persisted in 33 (17.4%) patients: 8 (9.9%) after redo-TAVI, 18 (25.9%) after plug, and 7 (21.9%) after valvuloplasty (P = 0.036). Overall mortality was 10 (5.0%) at 30 days and 29 (14.4%) at 1 year: 0, 8 (10.1%), and 2 (5.7%) at 30 days (P = 0.010) and 11 (12.6%), 14 (17.7%), and 4 (11.4%) at 1 year (P = 0.418), after redo-TAVI, plug, and valvuloplasty, respectively. Regardless of treatment strategy, patients in whom AR was reduced to ≤ mild had lower mortality at 1 year compared with those with AR persisting ≥ moderate [11 (8.0%) vs. 6 (21.4%); P = 0.007]. CONCLUSION: This study describes the efficacy of transcatheter treatments for PVR after TAVI. Patients in whom PVR was successfully reduced had better prognosis. The selection of patients and the optimal PVR treatment modality require further investigation.

Transfemoral tricuspid valve replacement and one-year outcomes: the TRISCEND study.

BACKGROUND AND AIMS: For patients with symptomatic, severe tricuspid regurgitation (TR), early results of transcatheter tricuspid valve (TV) intervention studies have shown significant improvements in functional status and quality of life associated with right-heart reverse remodelling. Longer-term follow-up is needed to confirm sustained improvements in these outcomes. METHODS: The prospective, single-arm, multicentre TRISCEND study enrolled 176 patients to evaluate the safety and performance of transcatheter TV replacement in patients with ≥moderate, symptomatic TR despite medical therapy. Major adverse events, reduction in TR grade and haemodynamic outcomes by echocardiography, and clinical, functional, and quality-of-life parameters are reported to one year. RESULTS: Enrolled patients were 71.0% female, mean age 78.7 years, 88.0% ≥ severe TR, and 75.4% New York Heart Association classes III-IV. Tricuspid regurgitation was reduced to ≤mild in 97.6% (P < .001), with increases in stroke volume (10.5 ± 16.8 mL, P < .001) and cardiac output (0.6 ± 1.2 L/min, P < .001). New York Heart Association class I or II was achieved in 93.3% (P < .001), Kansas City Cardiomyopathy Questionnaire score increased by 25.7 points (P < .001), and six-minute walk distance increased by 56.2 m (P < .001). All-cause mortality was 9.1%, and 10.2% of patients were hospitalized for heart failure. CONCLUSIONS: In an elderly, highly comorbid population with ≥moderate TR, patients receiving transfemoral EVOQUE transcatheter TV replacement had sustained TR reduction, significant increases in stroke volume and cardiac output, and high survival and low hospitalization rates with improved clinical, functional, and quality-of-life outcomes to one year. Funded by Edwards Lifesciences, TRISCEND ClinicalTrials.gov number, NCT04221490.

Five-Year Outcomes of Transcatheter or Surgical Aortic-Valve Replacement.

BACKGROUND: There are scant data on long-term clinical outcomes and bioprosthetic-valve function after transcatheter aortic-valve replacement (TAVR) as compared with surgical aortic-valve replacement in patients with severe aortic stenosis and intermediate surgical risk. METHODS: We enrolled 2032 intermediate-risk patients with severe, symptomatic aortic stenosis at 57 centers. Patients were stratified according to intended transfemoral or transthoracic access (76.3% and 23.7%, respectively) and were randomly assigned to undergo either TAVR or surgical replacement. Clinical, echocardiographic, and health-status outcomes were followed for 5 years. The primary end point was death from any cause or disabling stroke. RESULTS: At 5 years, there was no significant difference in the incidence of death from any cause or disabling stroke between the TAVR group and the surgery group (47.9% and 43.4%, respectively; hazard ratio, 1.09; 95% confidence interval [CI], 0.95 to 1.25; P = 0.21). Results were similar for the transfemoral-access cohort (44.5% and 42.0%, respectively; hazard ratio, 1.02; 95% CI, 0.87 to 1.20), but the incidence of death or disabling stroke was higher after TAVR than after surgery in the transthoracic-access cohort (59.3% vs. 48.3%; hazard ratio, 1.32; 95% CI, 1.02 to 1.71). At 5 years, more patients in the TAVR group than in the surgery group had at least mild paravalvular aortic regurgitation (33.3% vs. 6.3%). Repeat hospitalizations were more frequent after TAVR than after surgery (33.3% vs. 25.2%), as were aortic-valve reinterventions (3.2% vs. 0.8%). Improvement in health status at 5 years was similar for TAVR and surgery. CONCLUSIONS: Among patients with aortic stenosis who were at intermediate surgical risk, there was no significant difference in the incidence of death or disabling stroke at 5 years after TAVR as compared with surgical aortic-valve replacement. (Funded by Edwards Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313.).

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.

TAVR in TAVR: Where Are We in 2023 for Management of Failed TAVR Valves?

PURPOSE OF REVIEW: As TAVR is increasingly performed on younger patients with a longer life expectancy, the number of redo-TAVR procedures is likely to increase in the coming years. Limited data is currently available on this sometimes challenging procedure. We provide a summary of currently published literature on management of patients with a failed transcatheter aortic valve. RECENT FINDINGS: Recent registry data have increased the clinical knowledge on redo-TAVR. Additionally, numerous bench studies have provided valuable insights into the technical aspects of redo-TAVR with various combinations of valve types. Redo-TAVR can be performed safely in selected cases with a high procedural success and good short-term outcomes. However, at present, the procedure remains relatively infrequent and many patients are not eligible. Bench testing can be useful to understand important concepts such as valve expansion, neoskirt, leaflet overhang, and leaflet deflection as well as their potential clinical implications.

Update on Transcatheter Treatment of Mitral and Tricuspid Valve Regurgitation.

PURPOSE OF REVIEW: Mitral and tricuspid regurgitation represents a clinical challenge. They are associated with a poor prognosis, and many patients are not eligible for conventional surgery. Transcatheter therapies have been the focus of numerous studies and devices over the past decade. Here, we provide a summary of current options for transcatheter treatment of these 2 entities. RECENT FINDINGS: Recent studies have demonstrated the benefits of edge-to-edge repair for increasing numbers of patients. Encouraging early results with transcatheter valve replacement are also becoming available. To date, transcatheter edge-to-edge repair is currently the first-line transcatheter treatment for both mitral and tricuspid regurgitation for many patients who are not candidates for surgery. A number of transcatheter replacement devices are under development and clinical investigation but, for the most part, their current use is limited to compassionate cases or clinical trials.

[Tricuspid regurgitation in 2023 : Where are we with the treatment of the forgotten valve?] / Insuffisance tricuspide en 2023 : modalités de traitement pour la valve oubliée.

The negative impact of tricuspid regurgitation on prognosis in now well established. It also appears clear that surgical and possibly percutaneous treatment should be performed before reaching a point of no return with advanced heart failure and deterioration of right ventricle function. Percutaneous treatment has been divided into coaptation restoration devices, annuloplasty devices, and ortho- or heterotopic valve replacement. The present article offers a brief review of diagnostic modalities beyond echocardiography, surgical treatment as well as of the multiple recent development in the percutaneous treatment of this frequent condition.

L'impact pronostique défavorable de l'insuffisance tricuspide (IT) est maintenant bien établi, ainsi que la nécessité d'intervenir chirurgicalement ou de manière percutanée lorsque le traitement médicamenteux est insuffisant. Des données récentes suggèrent par ailleurs qu'il est probablement judicieux d'intervenir avant qu'un stade trop avancé d'insuffisance cardiaque et d'atteinte du ventricule droit ne soit atteint. Le traitement percutané est divisé en dispositifs de restauration de la coaptation valvulaire, d'annuloplastie et de remplacement de valve ortho ou hétérotopique. Cet article propose une brève revue des modalités diagnostiques au-delà de l'échocardiographie, du traitement chirurgical ainsi que des multiples développements récents dans le traitement percutané de cette pathologie fréquente.

Transcatheter Mitral Valve Replacement After Surgical Repair or Replacement: Comprehensive Midterm Evaluation of Valve-in-Valve and Valve-in-Ring Implantation From the VIVID Registry.

BACKGROUND: Mitral valve-in-valve (ViV) and valve-in-ring (ViR) are alternatives to surgical reoperation in patients with recurrent mitral valve failure after previous surgical valve repair or replacement. Our aim was to perform a large-scale analysis examining midterm outcomes after mitral ViV and ViR. METHODS: Patients undergoing mitral ViV and ViR were enrolled in the Valve-in-Valve International Data Registry. Cases were performed between March 2006 and March 2020. Clinical endpoints are reported according to the Mitral Valve Academic Research Consortium (MVARC) definitions. Significant residual mitral stenosis (MS) was defined as mean gradient ≥10 mm Hg and significant residual mitral regurgitation (MR) as ≥ moderate. RESULTS: A total of 1079 patients (857 ViV, 222 ViR; mean age 73.5±12.5 years; 40.8% male) from 90 centers were included. Median STS-PROM score 8.6%; median clinical follow-up 492 days (interquartile range, 76-996); median echocardiographic follow-up for patients that survived 1 year was 772.5 days (interquartile range, 510-1211.75). Four-year Kaplan-Meier survival rate was 62.5% in ViV versus 49.5% for ViR (P<0.001). Mean gradient across the mitral valve postprocedure was 5.7±2.8 mm Hg (≥5 mm Hg; 61.4% of patients). Significant residual MS occurred in 8.2% of the ViV and 12.0% of the ViR patients (P=0.09). Significant residual MR was more common in ViR patients (16.6% versus 3.1%; P<0.001) and was associated with lower survival at 4 years (35.1% versus 61.6%; P=0.02). The rates of Mitral Valve Academic Research Consortium-defined device success were low for both procedures (39.4% total; 32.0% ViR versus 41.3% ViV; P=0.01), mostly related to having postprocedural mean gradient ≥5 mm Hg. Correlates for residual MS were smaller true internal diameter, younger age, and larger body mass index. The only correlate for residual MR was ViR. Significant residual MS (subhazard ratio, 4.67; 95% CI, 1.74-12.56; P=0.002) and significant residual MR (subhazard ratio, 7.88; 95% CI, 2.88-21.53; P<0.001) were both independently associated with repeat mitral valve replacement. CONCLUSIONS: Significant residual MS and/or MR were not infrequent after mitral ViV and ViR procedures and were both associated with a need for repeat valve replacement. Strategies to improve postprocedural hemodynamics in mitral ViV and ViR should be further explored.

Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients.

BACKGROUND: Among patients with aortic stenosis who are at intermediate or high risk for death with surgery, major outcomes are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. There is insufficient evidence regarding the comparison of the two procedures in patients who are at low risk. METHODS: We randomly assigned patients with severe aortic stenosis and low surgical risk to undergo either TAVR with transfemoral placement of a balloon-expandable valve or surgery. The primary end point was a composite of death, stroke, or rehospitalization at 1 year. Both noninferiority testing (with a prespecified margin of 6 percentage points) and superiority testing were performed in the as-treated population. RESULTS: At 71 centers, 1000 patients underwent randomization. The mean age of the patients was 73 years, and the mean Society of Thoracic Surgeons risk score was 1.9% (with scores ranging from 0 to 100% and higher scores indicating a greater risk of death within 30 days after the procedure). The Kaplan-Meier estimate of the rate of the primary composite end point at 1 year was significantly lower in the TAVR group than in the surgery group (8.5% vs. 15.1%; absolute difference, -6.6 percentage points; 95% confidence interval [CI], -10.8 to -2.5; P<0.001 for noninferiority; hazard ratio, 0.54; 95% CI, 0.37 to 0.79; P = 0.001 for superiority). At 30 days, TAVR resulted in a lower rate of stroke than surgery (P = 0.02) and in lower rates of death or stroke (P = 0.01) and new-onset atrial fibrillation (P<0.001). TAVR also resulted in a shorter index hospitalization than surgery (P<0.001) and in a lower risk of a poor treatment outcome (death or a low Kansas City Cardiomyopathy Questionnaire score) at 30 days (P<0.001). There were no significant between-group differences in major vascular complications, new permanent pacemaker insertions, or moderate or severe paravalvular regurgitation. CONCLUSIONS: Among patients with severe aortic stenosis who were at low surgical risk, the rate of the composite of death, stroke, or rehospitalization at 1 year was significantly lower with TAVR than with surgery. (Funded by Edwards Lifesciences; PARTNER 3 ClinicalTrials.gov number, NCT02675114.).

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.

Complete revascularization in stable multivessel coronary artery disease: A real world analysis from the British Columbia Cardiac Registry.

BACKGROUND: More than half of patients undergoing percutaneous coronary intervention (PCI) have multivessel disease (MVD). The prognostic significance of PCI in stable patients has recently been debated, but little data exists about the potential benefit of complete revascularization (CR) in stable MVD. We investigated the prognostic benefit of CR in patients undergoing PCI for stable disease. METHODS: We compared CR versus incomplete revascularization (IR) in 8,436 patients with MVD. The primary outcome was all-cause mortality at 5 years. RESULTS: A total of 1,399 patients (17%) underwent CR during the index PCI procedure for stable disease. CR was associated with lower mortality (6.2 vs. 10.7%, p < .001) and lower repeat revascularization at 5 years (12.7 vs. 18.4%, p < .001). Multivariable-adjusted analyses indicated that CR was associated with lower mortality (HR = 0.73, 95% CI: 0.58-0.91, p = .005) and repeat revascularization at 5 years (HR = 0.78, 95% CI: 0.66-0.93, p = .005). These findings were also confirmed in propensity-matched cohorts. Subgroup analyses indicated that CR conferred survival in older patients, male patients, absence of renal disease, greater angina (CCS Class III-IV) and heart failure (NYHA Class III-IV) symptoms, and greater burden of coronary disease. In sensitivity analyses where patients with subsequent repeat revascularization events were excluded, CR remained a strong predictor for lower mortality (HR = 0.69, 95% CI: 0.54-0.89, p = .004). CONCLUSIONS: In this study of stable patients with MVD, CR was an independent predictor of long-term survival. This benefit was specifically seen in higher risk patient groups and indicates that CR may benefit selected stable patients with MVD.

Transcatheter Aortic Valve Implantation with ACURATE neo: Results from the PROGRESS PVL Registry.

Objectives: The PROGRESS PVL registry evaluated transcatheter aortic valve implantation (TAVI) in patients treated with ACURATE neo, a supra-annular self-expanding bioprosthetic aortic valve. Background: While clinical outcomes with TAVI are comparable with those achieved with surgery, residual aortic regurgitation (AR) and paravalvular leak (PVL) are common complications. The ACURATE neo valve has a pericardial sealing skirt designed to minimize PVL. Methods: The primary endpoint was the rate of total AR over time, as assessed by a core echocardiographic laboratory. The study enrolled 500 patients (mean age: 81.8 ± 5.1 years; 61% female; mean baseline STS score: 6.0 ± 4.5%) from 22 centers in Europe and Canada; 498 patients were treated with ACURATE neo. Results: The rate of ≥ moderate AR was 4.6% at discharge and 3.1% at 12 months; the rate of ≥ moderate PVL was 4.6% at discharge and 2.6% at 12 months. Paired analyses showed significant improvement in overall PVL between discharge and 12 months (P < 0.001); 64.6% of patients had no change in PVL grade, 24.9% improved, and 10.5% worsened. Patients also exhibited significant improvement in transvalvular gradient (P < 0.001) and effective orifice area (P=0.01). The mortality rate was 2.2% at 30 days and 11.3% at 12 months. The permanent pacemaker implantation (PPI) rate was 10.2% at 30 days and 12.2% at 12 months. Conclusions: Results from PROGRESS PVL support the sustained safety and performance of TAVI with the ACURATE neo valve, showing excellent valve hemodynamics, good clinical outcomes, and significant interindividual improvement in PVL from discharge to 12-month follow-up.

Antibody Seroprevalence, Infection and Surveillance for SARS-CoV-2 in Residents and Staff of New Jersey Long-Term Care Facilities.

Early in the pandemic, New Jersey (NJ) long-term care facilities (LTCFs) witnessed severe COVID-19 illness. With limited surveillance to characterize the scope of infection, we estimated the prevalence of antibody to the SARS-CoV-2 nucleocapsid protein among residents and staff, to describe the epidemiology, and to measure antibody distribution by prior PCR/antigen status and symptomatology. 10 NJ LTCFs of 20 solicited with diverse geography and bed-capacities were visited between October 2020 and March 2021. A single serum was tested for total N-antibody (ELISA) by the state laboratory. Residents' demographics and clinical history were transcribed from the patient record. For staff, this information was solicited directly from employees, supplemented by prior PCR/antigen results from facilities. 62% of 332 residents and 46% of 661 staff tested N-antibody positive. In a multivariable logistic regression in residents, odds ratios for older age and admission prior before March 1, 2020 were significant. Among the staff, odds ratios for older age, ethnic-racial group, nursing-related job, and COVID-19 symptoms were significantly associated with N-antibody positivity. In a sub-analysis in five better record-keeping LTCFs, 90% of residents and 85% of staff with positive PCR/antigen results were seropositive for N-antibody, yet 25% of residents and 22% of staff were N-antibody positive but PCR/antigen and symptoms negative. The high rate of clinically unsuspected infections likely contributed to the spread. These findings argue for robust surveillance, regular screening of asymptomatic individuals, and vaccinating both residents and staff to abate the pandemic. The data also provide guidance to prevent future outbreaks.

Valve Academic Research Consortium 3: updated endpoint definitions for aortic valve clinical research.

AIMS: The Valve Academic Research Consortium (VARC), founded in 2010, was intended to (i) identify appropriate clinical endpoints and (ii) standardize definitions of these endpoints for transcatheter and surgical aortic valve clinical trials. Rapid evolution of the field, including the emergence of new complications, expanding clinical indications, and novel therapy strategies have mandated further refinement and expansion of these definitions to ensure clinical relevance. This document provides an update of the most appropriate clinical endpoint definitions to be used in the conduct of transcatheter and surgical aortic valve clinical research. METHODS AND RESULTS: Several years after the publication of the VARC-2 manuscript, an in-person meeting was held involving over 50 independent clinical experts representing several professional societies, academic research organizations, the US Food and Drug Administration (FDA), and industry representatives to (i) evaluate utilization of VARC endpoint definitions in clinical research, (ii) discuss the scope of this focused update, and (iii) review and revise specific clinical endpoint definitions. A writing committee of independent experts was convened and subsequently met to further address outstanding issues. There were ongoing discussions with FDA and many experts to develop a new classification schema for bioprosthetic valve dysfunction and failure. Overall, this multi-disciplinary process has resulted in important recommendations for data reporting, clinical research methods, and updated endpoint definitions. New definitions or modifications of existing definitions are being proposed for repeat hospitalizations, access site-related complications, bleeding events, conduction disturbances, cardiac structural complications, and bioprosthetic valve dysfunction and failure (including valve leaflet thickening and thrombosis). A more granular 5-class grading scheme for paravalvular regurgitation (PVR) is being proposed to help refine the assessment of PVR. Finally, more specific recommendations on quality-of-life assessments have been included, which have been targeted to specific clinical study designs. CONCLUSIONS: Acknowledging the dynamic and evolving nature of less-invasive aortic valve therapies, further refinements of clinical research processes are required. The adoption of these updated and newly proposed VARC-3 endpoints and definitions will ensure homogenous event reporting, accurate adjudication, and appropriate comparisons of clinical research studies involving devices and new therapeutic strategies.

The Impact of Pre-Procedural Renal Impairment on Outcomes Following Percutaneous Coronary Intervention: An Analysis of 45,287 Patients From the British Columbia Cardiac Registry.

BACKGROUND: Renal disease confers a strong independent risk for morbidity and mortality after percutaneous coronary intervention (PCI). We evaluated the relationship between baseline pre-procedural renal function and outcomes following PCI. METHODS: We examined 45,287 patients who underwent PCI in British Columbia. We evaluated all-cause mortality and target vessel revascularisation (TVR) at 2 years. Pre-procedural renal impairment was categorised by creatinine clearance (CrCl, mL/min): CrCl≥90 (n=14,876), 90>CrCl≥60 (n=10,219), 60>CrCl≥30 (n=14,876), 30>CrCl≥0 (n=2,594) and dialysis (n=579). RESULTS: Declining CrCl values less than 60 mL/min were progressively associated with greater mortality: 60>eGFR≥30 (HR=2.01, 95% CI 1.71-2.37, p<0.001); 30>eGFR≥0 (HR=4.10, 95% CI 3.39-4.95, p<0.001); and dialysis (HR=6.22, 95% CI 5.07-7.63, p<0.001). A reduction in eGFR was not associated with TVR in non-dialysis patients. However, dialysis was a strong independent predictor for TVR (HR=1.69, 95% CI 1.37-2.08, p<0.001). This was confirmed in propensity-matched analyses where, dialysis was strongly associated with TVR (HR=1.53, 95% CI 1.24-1.89, p<0.001). This association was consistently seen in stratified analyses for diabetic versus non-diabetic patients; stent length >30 mm versus <30 mm; stent diameter >3 mm versus <3 mm; and receipt of bare metal stents versus drug-eluting stents. CONCLUSIONS: This study indicates the association with declining renal function and mortality in patients undergoing PCI. Whilst renal disease was not associated with increased TVR in non-dialysis patients, dialysis-dependence was a strong independent predictor for increased TVR.