Characterizing stay-green in barley across diverse environments: unveiling novel haplotypes.

KEY MESSAGE: There is variation in stay-green within barley breeding germplasm, influenced by multiple haplotypes and environmental conditions. The positive genetic correlation between stay-green and yield across multiple environments highlights the potential as a future breeding target. Barley is considered one of the most naturally resilient crops making it an excellent candidate to dissect the genetics of drought adaptive component traits. Stay-green, is thought to contribute to drought adaptation, in which the photosynthetic machinery is maintained for a longer period post-anthesis increasing the photosynthetic duration of the plant. In other cereal crops, including wheat, stay-green has been linked to increased yield under water-limited conditions. Utilizing a panel of diverse barley breeding lines from a commercial breeding program we aimed to characterize stay-green in four environments across two years. Spatiotemporal modeling was used to accurately model senescence patterns from flowering to maturity characterizing the variation for stay-green in barley for the first time. Environmental effects were identified, and multi-environment trait analysis was performed for stay-green characteristics during grain filling. A consistently positive genetic correlation was found between yield and stay-green. Twenty-two chromosomal regions with large effect haplotypes were identified across and within environment types, with ten being identified in multiple environments. In silico stacking of multiple desirable haplotypes showed an opportunity to improve the stay-green phenotype through targeted breeding. This study is the first of its kind to model barley stay-green in a large breeding panel and has detected novel, stable and environment specific haplotypes. This provides a platform for breeders to develop Australian barley with custom senescence profiles for improved drought adaptation.

Residual tricuspid regurgitation after tricuspid transcatheter edge-to-edge repair: Insights into the EuroTR registry.

AIMS: Data on the prognostic impact of residual tricuspid regurgitation (TR) after tricuspid transcatheter edge-to-edge repair (T-TEER) are scarce. The aim of this analysis was to evaluate 2-year survival and symptomatic outcomes of patients in relation to residual TR after T-TEER. METHODS AND RESULTS: Using the large European Registry of Transcatheter Repair for Tricuspid Regurgitation (EuroTR registry) we investigated the impact of residual TR on 2-year all-cause mortality and New York Heart Association (NYHA) functional class at follow-up. The study further identified predictors for residual TR ≥3+ using a logistic regression model. The study included a total of 1286 T-TEER patients (mean age 78.0 ± 8.9 years, 53.6% female). TR was successfully reduced to ≤1+ in 42.4%, 2+ in 40.0% and 3+ in 14.9% of patients at discharge, while 2.8% remained with TR ≥4+ after the procedure. Residual TR ≥3+ was an independent multivariable predictor of 2-year all-cause mortality (hazard ratio 2.06, 95% confidence interval 1.30-3.26, p = 0.002). The prevalence of residual TR ≥3+ was four times higher in patients with higher baseline TR (vena contracta >11.1 mm) and more severe tricuspid valve tenting (tenting area >1.92 cm2). Of note, no survival difference was observed in patients with residual TR ≤1+ versus 2+ (76.2% vs. 73.1%, p = 0.461). The rate of NYHA functional class ≥III at follow-up was significantly higher in patients with residual TR ≥3+ (52.4% vs. 40.5%, p < 0.001). Of note, the degree of TR reduction significantly correlated with the extent of symptomatic improvement (p = 0.012). CONCLUSIONS: T-TEER effectively reduced TR severity in the majority of patients. While residual TR ≥3+ was associated with worse outcomes, no differences were observed for residual TR 1+ versus 2+. Symptomatic improvement correlated with the degree of TR reduction.

Comparison of two self-expanding transcatheter heart valves for degenerated surgical bioprostheses: the AVENGER multicentre registry.

BACKGROUND: There is a lack of comparative data on transcatheter aortic valve implantation (TAVI) in degenerated surgical prostheses (valve-in-valve [ViV]). AIMS: We sought to compare outcomes of using two self-expanding transcatheter heart valve (THV) systems for ViV. METHODS: In this retrospective multicentre registry, we included consecutive patients undergoing transfemoral ViV using either the ACURATE neo/neo2 (ACURATE group) or the Evolut R/PRO/PRO+ (EVOLUT group). The primary outcome measure was technical success according to Valve Academic Research Consortium (VARC)-3. Secondary outcomes were 30-day all-cause mortality, device success (VARC-3), coronary obstruction (CO) requiring intervention, rates of severe prosthesis-patient mismatch (PPM), and aortic regurgitation (AR) ≥moderate. Comparisons were made after 1:1 propensity score matching. RESULTS: The study cohort comprised 835 patients from 20 centres (ACURATE n=251; EVOLUT n=584). In the matched cohort (n=468), technical success (ACURATE 92.7% vs EVOLUT 88.9%; p=0.20) and device success (69.7% vs 73.9%; p=0.36) as well as 30-day mortality (2.8% vs 1.6%; p=0.392) were similar between the two groups. The mean gradients and rates of severe PPM, AR ≥moderate, or CO did not differ between the groups. Technical and device success were higher for the ACURATE platform among patients with a true inner diameter (ID) >19 mm, whereas a true ID ≤19 mm was associated with higher device success - but not technical success - among Evolut recipients. CONCLUSIONS: ViV TAVI using either ACURATE or Evolut THVs showed similar procedural outcomes. However, a true ID >19 mm was associated with higher device success among ACURATE recipients, whereas in patients with a true ID ≤19 mm, device success was higher when using Evolut.

Long-Term Outcomes After Transcatheter Aortic Valve Implantation in Patients With Chronic Inflammatory Disease.

BACKGROUND: Chronic inflammatory disease (CID) accelerates atherosclerosis and the development of aortic stenosis. Data on long-term outcomes after transcatheter aortic valve implantation (TAVI) in those patients are missing. The aim of this study was to investigate the clinical long-term outcomes of patients with and without autoimmune-related CID undergoing TAVI for the treatment of severe aortic stenosis. METHODS AND RESULTS: From a prospective registry, consecutive patients with TAVI were included. Baseline clinic and imaging data (echocardiographic and computed tomography) were analyzed. Long-term (up to 5 years) clinical and echocardiographic outcomes were studied. Of 1000 consecutive patients (mean age 81±6 years, 46% female), 107 (11%) had CID; the most frequent entities included polymyalgia rheumatica (31%) and rheumatoid arthritis (28%). Patients with CID were predominantly female (60% versus 44%, P=0.002) and more often had pulmonary disorders (21% versus 13%, P=0.046) and atrial fibrillation (32% versus 20%, P=0.003). The presence of CID was associated with a higher rate of postinterventional infection (5% versus 1%, P=0.007) and further emerged as a risk factor for rehospitalization for bleeding or infection (hazard ratio, 1.93 and 1.62, respectively). Premature valve degeneration, endocarditis, and all-cause mortality were not increased among patients with CID. CONCLUSIONS: This real-world analysis found that patients with CID undergoing TAVI were associated with a higher risk of postinterventional infectious complications and rehospitalization due to infection. However, valve durability and survival seem not to differ between patients with TAVI with versus without CID.

Incidence, Predictors, and Prognostic Impact of New Permanent Pacemaker Implantation After TAVR With Self-Expanding Valves.

OBJECTIVES: The authors sought to evaluate the incidence, predictors, and outcomes of new permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) with contemporary self-expanding valves (SEV). BACKGROUND: Need for PPI is frequent post-TAVR, but conflicting data exist on new-generation SEV and on the prognostic impact of PPI. METHODS: This study included 3,211 patients enrolled in the multicenter NEOPRO (A Multicenter Comparison of Acurate NEO Versus Evolut PRO Transcatheter Heart Valves) and NEOPRO-2 (A Multicenter Comparison of ACURATE NEO2 Versus Evolut PRO/PRO+ Transcatheter Heart Valves 2) registries (January 2012 to December 2021) who underwent transfemoral TAVR with SEV. Implanted transcatheter heart valves (THV) were Acurate neo (n = 1,090), Acurate neo2 (n = 665), Evolut PRO (n = 1,312), and Evolut PRO+ (n = 144). Incidence and predictors of new PPI and 1-year outcomes were evaluated. RESULTS: New PPI was needed in 362 patients (11.3%) within 30 days after TAVR (8.8%, 7.7%, 15.2%, and 10.4%, respectively, after Acurate neo, Acurate neo2, Evolut PRO, and Evolut PRO+). Independent predictors of new PPI were Society of Thoracic Surgeons Predicted Risk of Mortality score, baseline right bundle branch block and depth of THV implantation, both in patients treated with Acurate neo/neo2 and in those treated with Evolut PRO/PRO+. Predischarge reduction in ejection fraction (EF) was more frequent in patients requiring PPI (P = 0.014). New PPI was associated with higher 1-year mortality (16.9% vs 10.8%; adjusted HR: 1.66; 95% CI: 1.13-2.43; P = 0.010), particularly in patients with baseline EF <40% (P for interaction = 0.049). CONCLUSIONS: New PPI was frequently needed after TAVR with SEV (11.3%) and was associated with higher 1-year mortality, particularly in patients with EF <40%. Baseline right bundle branch block and depth of THV implantation independently predicted the need of PPI.

Incidence, predictors, and prognostic impact of new permanent pacemaker implantation after TAVR with self-expanding valves

OBJECTIVES: The authors sought to evaluate the incidence, predictors, and outcomes of new permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) with contemporary self-expanding valves (SEV). BACKGROUND: Need for PPI is frequent post-TAVR, but conflicting data exist on new-generation SEV and on the prognostic impact of PPI. METHODS: This study included 3,211 patients enrolled in the multicenter NEOPRO (A Multicenter Comparison of Acurate NEO Versus Evolut PRO Transcatheter Heart Valves) and NEOPRO-2 (A Multicenter Comparison of ACURATE NEO2 Versus Evolut PRO/PRO+ Transcatheter Heart Valves 2) registries (January 2012 to December 2021) who underwent transfemoral TAVR with SEV. Implanted transcatheter heart valves (THV) were Acurate neo (n = 1,090), Acurate neo2 (n = 665), Evolut PRO (n = 1,312), and Evolut PRO+ (n = 144). Incidence and predictors of new PPI and 1-year outcomes were evaluated. RESULTS: New PPI was needed in 362 patients (11.3%) within 30 days after TAVR (8.8%, 7.7%, 15.2%, and 10.4%, respectively, after Acurate neo, Acurate neo2, Evolut PRO, and Evolut PRO+). Independent predictors of new PPI were Society of Thoracic Surgeons Predicted Risk of Mortality score, baseline right bundle branch block and depth of THV implantation, both in patients treated with Acurate neo/neo2 and in those treated with Evolut PRO/PRO+. Predischarge reduction in ejection fraction (EF) was more frequent in patients requiring PPI (P = 0.014). New PPI was associated with higher 1-year mortality (16.9% vs 10.8%; adjusted HR: 1.66; 95% CI: 1.13-2.43; P = 0.010), particularly in patients with baseline EF <40% (P for interaction = 0.049). CONCLUSIONS: New PPI was frequently needed after TAVR with SEV (11.3%) and was associated with higher 1-year mortality, particularly in patients with EF <40%. Baseline right bundle branch block and depth of THV implantation independently predicted the need of PPI.

Hypoattenuated Leaflet Thickening After Implantation of the ACURATE neo or the ACURATE neo2 Transcatheter Heart Valve.

Subclinical leaflet thrombosis, identified as hypoattenuated leaflet thickening (HALT) on cardiac computed tomography scan, has been observed after transcatheter aortic valve replacement (TAVR). However, data on HALT after the implant of the supra-annular ACURATE neo/neo2 prosthesis are limited. This study aimed to determine the prevalence and risk factors for the development of HALT after TAVR with the ACURATE neo/neo2. A total of 50 patients who received the ACURATE neo/neo2 prosthesis were prospectively enrolled. Patients underwent a contrast-enhanced multidetector row cardiac computed tomography scan at before, after, and 6 months after TAVR. At the 6-month follow-up, HALT was detected in 16% (8 of 50 patients). These patients had a lower implant depth of the transcatheter heart valve (8 ± 2 mm vs 5 ± 2 mm, p = 0.001), less calcified native valve leaflets, a better expansion of the frame at the level of the left ventricular outflow tract, and were less often hypertensive. Thrombosis of the sinus of Valsalva occurred in 18% (9/50). There was no difference in the anticoagulation regimen between patients with and without thrombotic findings. In conclusion, HALT was present in 16% of patients at 6 months follow-up, patients presenting with HALT had a lower implant depth of the transcatheter heart valve, and HALT was detected in patients on oral anticoagulation therapy.

Tricuspid Regurgitation and Right Ventricular Function in Patients Undergoing Percutaneous Treatment of Mitral Regurgitation.

OBJECTIVES: Patients with severe mitral regurgitation (MR) frequently present with concomitant right ventricular (RV) dysfunction and tricuspid regurgitation (TR). We aimed to investigate the prognostic relevance of RV function, RV dimension, and TR in patients undergoing percutaneous intervention for MR. METHODS: Consecutive patients undergoing percutaneous mitral valve intervention were enrolled in the prospective MitraSwiss registry. Tricuspid annular plane systolic excursion (TAPSE), pulmonary artery systolic pressure (PASP), right ventricular pulmonary arterial coupling (RVC, defined as TAPSE/ PASP ratio), indexed tricuspid annulus (TA) dimension, and TR severity grade were analyzed at baseline, post procedure, and at 6-month follow-up. The endpoints of all-cause mortality, hospitalization for heart failure, and the combined endpoint of the 2 were observed during long-term follow-up (up to 4 years). RESULTS: We analyzed 218 patients (mean age, 76 ± 9 years; 36% female). Edge-to-edge mitral valve repair resulted in an increase in TAPSE and RVC ratio and a decrease in indexed TA and PASP, but concomitant TR did not change significantly. In multivariable analysis, RV dysfunction and moderate/severe TR were independently associated with increased all-cause mortality (hazard ratio, 1.61; 95% confidence interval, 1.05-2.46; P=.03 and hazard ratio, 2.10; 95% confidence interval, 1.34-3.29; P<.01, respectively) and moderate/severe TR was further an independent predictor for hospitalization for heart failure and for the combined endpoint. CONCLUSION: Treatment of MR resulted in favorable changes of RV function and dimension but did not reduce TR in the majority of patients. TR at baseline remained the strongest predictor for outcomes, outperforming parameters of RV function and dimension.

The relevance of tricuspid regurgitation in patients undergoing percutaneous treatment of mitral regurgitation.

OBJECTIVES: Investigate the impact of concomitant tricuspid regurgitation (TR) on clinical outcomes during long-term follow-up in patients undergoing percutaneous treatment of mitral regurgitation (MR) with the MitraClip system. BACKGROUND: Patients undergoing mitral repair using the MitraClip frequently present with concomitant TR. It is uncertain how the presence of TR impacts the long-term outcomes of such patients. METHODS: We analyzed consecutive patients with MitraClip implantation from the prospective MitraSwiss registry. Endpoints were all-cause mortality, hospitalization for heart failure, and the composite endpoint of the two. RESULTS: We enrolled 177 patients (mean age 76 ± 9 years, 37% female). Acute procedural success was achieved in 149 (84%). Concomitant moderate or severe TR was present in 31% at baseline and 32% before discharge. After a median follow-up of 1103 days (IQR: 555-1766 days), 70 (40%) of patients had died, and 34 (19%) were hospitalized for heart failure. In multivariable analysis, TR at baseline was associated with an increase in all-cause mortality (HR: 2.34, 95% CI: 1.36-4.03, p < 0.01), hospitalization for heart failure (HR: 3.19, 95% CI: 1.37-7.41, p = 0.01), and the composite endpoint (HR: 2.00, 95% CI: 1.19-3.36, p = 0.01). CONCLUSION: Despite treatment of MR, TR did not improve in most patients. The presence of relevant TR at baseline was associated with reduced survival and higher rates of hospitalization for heart failure. More research is needed to understand the causal role of TR in such patients and to investigate if simultaneous treatment of concomitant TR may improve prognosis in patients undergoing percutaneous treatment of MR.

V5/MT+ modulates spatio-temporal integration differently across and within hemifields: Causal evidence from TMS.

It is unclear how the brain reaches the correct balance between temporal and spatial processing necessary to perceive motion across space. Here, we tested whether visual motion area V5/MT + plays a causal role in Ternus illusion. Ternus displays can be perceived as showing either group motion or element motion and are empirically useful for dissociating temporal and spatial grouping across visual fields. Online single-pulse TMS was applied to observers during the presentation of Ternus displays, either within or across hemifields, over left V5/MT + or, respectively, a control site in the left somatosensory cortex, or an additional 'Sham' control condition. In the cross-hemifields condition, observers perceived more element motion with TMS over left V5/MT + than in either control condition. By contrast, in the within-hemifield condition, observers reported more group motion after left V5/MT + TMS. Our findings demonstrate a causal role of left V5/MT+ in the spatio-temporal grouping of Ternus apparent motion, and in maintaining the balance of spatio-temporal processing both within and across individual hemifields.