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Interlayer excitons (ILXs) — electron–hole pairs bound across two atomically thin layered semiconductors — have emerged as attractive platforms to study exciton condensation 1 – 4 , single-photon emission and other quantum information applications 5 – 7 . Yet, despite extensive optical spectroscopic investigations 8 – 12 , critical information about their size, valley configuration and the influence of the moiré potential remains unknown. Here, in a WSe 2 /MoS 2 heterostructure, we captured images of the time-resolved and momentum-resolved distribution of both of the particles that bind to form the ILX: the electron and the hole. We thereby obtain a direct measurement of both the ILX diameter of around 5.2 nm, comparable with the moiré-unit-cell length of 6.1 nm, and the localization of its centre of mass. Surprisingly, this large ILX is found pinned to a region of only 1.8 nm diameter within the moiré cell, smaller than the size of the exciton itself. This high degree of localization of the ILX is backed by Bethe–Salpeter equation calculations and demonstrates that the ILX can be localized within small moiré unit cells. Unlike large moiré cells, these are uniform over large regions, allowing the formation of extended arrays of localized excitations for quantum technology. Imaging the electron and hole that bind to form interlayer excitons in a 2D moiré material enables direct measurement of its diameter and indicates the localization of its centre of mass.

Background The transthoracic echocardiographic (TTE) evaluation of the severity of residual aortic regurgitation (AR) following transcatheter aortic valve implantation (TAVI) has been controversial and lacks validation. Objectives This study sought to compare TTE and cardiac magnetic resonance (CMR) for assessment of AR in patients undergoing TAVI with a balloon-expandable valve. Methods TTE and CMR exams were performed pre-TAVI in 50 patients and were repeated postprocedure in 42 patients. All imaging data were analysed in centralised core laboratories. Results The severity of native AR as determined by multiparametric TTE approach correlated well with the regurgitant volume and regurgitant fraction determined by CMR prior to TAVI (Rs=0.79 and 0.80, respectively; p<0.001 for both). However, after TAVI, the correlation between the prosthetic AR severity assessed by TTE and regurgitant volume and fraction measured by CMR was only modest (Rs=0.59 and 0.59, respectively; p<0.001 for both), with an underestimation of AR severity by TTE in 61.9% of patients (1 grade in 59.5%). The TTE jet diameter in parasternal view and the multiparametric approach (Rs=0.62 and 0.59, respectively; both with p<0.001) showed the best correlation with CMR regurgitant fraction post-TAVI. The circumferential extent of prosthetic paravalvular regurgitation showed a poor correlation with CMR regurgitant volume and fraction (Rs=0.32, p=0.084; Rs=0.36, p=0.054, respectively). Conclusions The severity of AR following TAVI with a balloon-expandable valve was underestimated by echocardiography as compared with CMR. The jet diameter, but not the circumferential extent of the leaks, and the multiparametric echocardiography integrative approach best correlated with CMR findings. These results provide important insight into the evaluation of AR severity post-TAVI.

The SAPIEN 3 valve (S3V) is a new-generation transcatheter valve with enhanced anti-paravalvular leak properties, but no data comparing with earlier transcatheter valve systems are available. We aimed to compare the hemodynamic performance of the S3V and the SAPIEN XT valve (SXTV) in a case-matched study with echo core laboratory analysis. A total of 27 patients who underwent transcatheter aortic valve replacement (TAVR) with the S3V were matched for prosthesis size (26 mm), aortic annulus area, and mean diameter measured by computed tomography, left ventricular ejection fraction, body surface area, and body mass index with 50 patients treated with the SXTV. The prosthesis size was determined by oversizing of 1% to 15% of annulus area. Doppler echocardiographic images collected at baseline and 1-month follow-up were analyzed in a central echocardiography core laboratory. The need for postdilation was higher in the SXTV group (20% vs 4%, p = 0.047), and mean residual gradient and effective orifice area were similar in both groups (p >0.05). The incidence of paravalvular aortic regurgitation was greater with the SXTV (≥mild: 42%, moderate: 8%) than with the S3V (≥mild: 7%, moderate: 0%; p = 0.002 for ≥mild vs SXTV). The implantation of an S3V was the only factor associated with trace or no paravalvular leak after TAVR (p = 0.007). In conclusion, TAVR with the S3V was associated with a very low rate of paravalvular leaks and need for balloon postdilation, much lower than that observed with the earlier generation of balloon-expandable valve (SXTV). The confirmation of these results in a larger cohort of patients will represent a major step forward in using transcatheter valves for the treatment of aortic stenosis. •Despite major improvements in aortic annulus measurements and valve sizing, the occurrence of paravalvular leaks remains one of the most important challenges of transcatheter aortic valve implantation (TAVI).•The present case-matched study with central echo core laboratory analysis showed a major reduction in the occurrence and severity of residual aortic regurgitation after TAVI with a new-generation balloon-expandable valve with enhanced anti-paravalvular leak properties (SAPIEN 3) compared with an earlier generation transcatheter valve (SAPIEN XT). Also, the SAPIEN 3 valve was associated with a significant reduction in the need for balloon postdilation after TAVI.

Chronic kidney disease is commonly found in patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) and has marked impact in their prognosis. It has been shown however that TAVR may improve renal function by alleviating the hemodynamic barrier imposed by AS. Nevertheless, the predictors of and clinical consequences of renal function improvement are not well established. Our aim was to assess the predictors of improvement of renal function after TAVR. The present work is an analysis of the Brazilian Registry of TAVR, a national non-randomized prospective study with 22 Brazilian centers. Patients with baseline renal dysfunction (estimated glomerular filtration rate [eGFR] < 60mL/min/1.73m2) were stratified according to renal function after TAVR: increase >10% in eGFR were classified as TAVR induced renal function improvement (TIRFI); decrease > 10% in eGFR were classified as acute kidney injury (AKI) and stable renal function (neither criteria). A total of 819 consecutive patients with symptomatic severe AS were included. Of these, baseline renal dysfunction (estimated glomerular filtration rate [eGFR] < 60mL/min/1.73m2) was present in 577 (70%) patients. Considering variance in renal function between baseline and at discharge after TAVR procedure, TIRFI was seen in 197 (34.1%) patients, AKI in 203 (35.2%), and stable renal function in 177 (30.7%). The independent predictors of TIRFI were: absence of coronary artery disease (OR: 0.69; 95% CI 0.48-0.98; P = 0.039) and lower baseline eGFR (OR: 0.98; 95% CI 0.97-1.00; P = 0.039). There was no significant difference in 30-day and 1-year all-cause mortality between patients with stable renal function or TIRFI. Nonetheless, individuals that had AKI after TAVR presented higher mortality compared with TIRFI and stable renal function groups (29.3% vs. 15.4% vs. 9.5%, respectively; p < 0.001). TIRFI was frequently found among baseline impaired renal function individuals but was not associated with improved 1-year outcomes.

Little is known about the usefulness of evaluating cardiac neurohormones in patients undergoing transcatheter aortic valve implantation (TAVI). The objectives of this study were to evaluate the baseline values and serial changes of N-terminal prohormone B-type natriuretic peptide (NT-proBNP) after TAVI, its related factors, and prognostic value. A total of 333 consecutive patients were included, and baseline, procedural, and follow-up (median 20 months, interquartile range 9 to 36) data were prospectively collected. Systematic NT-proBNP measurements were performed at baseline, hospital discharge, 1, 6, and 12 months, and yearly thereafter. Baseline NT-proBNP values were elevated in 86% of the patients (median 1,692 pg/ml); lower left ventricular ejection fraction and stroke volume index, greater left ventricular mass, and renal dysfunction were associated with greater baseline values (p <0.01 for all). Higher NT-proBNP levels were independently associated with increased long-term overall and cardiovascular mortalities (p <0.001 for both), with a baseline cut-off level of ∼2,000 pg/ml best predicting worse outcomes (p <0.001). At 6- to 12-month follow-up, NT-proBNP levels had decreased (p <0.001) by 23% and remained stable up to 4-year follow-up. In 39% of the patients, however, there was a lack of NT-proBNP improvement, mainly related to preprocedural chronic atrial fibrillation, lower mean transaortic gradient, and moderate-to-severe mitral regurgitation (p <0.01 for all). In conclusion, most patients undergoing TAVI presented high NT-proBNP levels, and a lack of improvement was observed in >1/3 of the patients after TAVI. Also, higher NT-proBNP levels predicted greater overall and cardiac mortalities at a median follow-up of 2 years. These findings support the implementation of NT-proBNP measurements for the clinical decision-making process and follow-up of patients undergoing TAVI.

The objectives of this study were to determine the causes and impact of anemia and hemoglobin level on functional status, physical performance, and quality of life in the preprocedural evaluation and follow-up of transcatheter aortic valve replacement (TAVR) candidates. A total of 438 patients who underwent TAVR were included. Anemia was defined as a hemoglobin level <12 g/dl in women and <13 g/dl in men. Before TAVR, anemia was encountered in 282 patients (64.4%). A potential treatable cause of anemia was detected in 90.4% of patients and was attributed to iron deficiency in 53% of them. The occurrence of anemia was an independent predictor of poorer performance in the 6-minute walk test (6MWT), a lower Duke Activity Status Index score, and Kansas City Cardiomyopathy Questionnaires overall, clinical, and social limitation scores (p <0.05 for all). A lower hemoglobin level was associated with a higher prevalence of New York Heart Association class III to IV (p <0.001) and correlated negatively with the results of all functional tests (p <0.02 for all). At follow-up, anemia was found in 62% of patients and was associated with poorer performance in the 6MWT (p = 0.023). A lower hemoglobin level after TAVR was a predictor of poorer New York Heart Association class (p = 0.020) and correlated negatively with the distance walked in the 6MWT (r = −0.191, p = 0.004) and Duke Activity Status Index score (r = −0.158, p = 0.011) at 6-month follow-up. In conclusion, anemia was very common in TAVR candidates and was attributed to iron deficiency in more than half of them. The presence of anemia and lower hemoglobin levels determined poorer functional status before and after the TAVR procedure. These results highlight the importance of implementing appropriate measures for the diagnosis and treatment of this frequent co-morbidity to improve both the accuracy of preprocedural evaluation and outcomes of TAVR candidates.

ObjectiveLow flow (LF), defined as stroke volume index (SVi) <35 mL/m2, prior to the procedure has been recently identified as a powerful independent predictor of early and late mortality in patients undergoing transcatheter aortic valve replacement (TAVR). The objectives of this study were to determine the evolution of SVi following TAVR and to assess the determinants and impact on mortality of early postprocedural SVi (EP-SVi).MethodsWe retrospectively analysed the clinical, Doppler echocardiographic and outcome data prospectively collected in 255 patients who underwent TAVR. Echocardiograms were performed before (baseline), within 5 days after procedure (early post procedure) and 6 months to 1 year following TAVR (late post procedure).ResultsPatients with EP-SVi <35 mL/m2 (n=138; 54%) had increased mortality (HR 1.97, p=0.003) compared with those with EP-SVi ≥35 mL/m2 (n=117; 46%). Furthermore, patients with baseline SVi (B-SVi) <35 mL/m2 and EP-SVI ≥35 mL/m2, that is, normalised flow, had better survival (HR 0.46, p=0.03) than those with both B-SVi and EP-SVi <35 mL/m2, that is, persistent LF, and similar survival compared with those with both B-SVi and EP-SVi ≥35 mL/m2, that is, maintained normal flow. In a multivariable model analysis, EP-SVi was independently associated with increased risk of mortality (HR 1.41 per 10 mL/m2 decrease, p=0.03). The preprocedural/intraprocedural factors associated with lower EP-SVi were lower B-SVi (standardised β [β] 0.36, p<0.001) atrial fibrillation (β −0.13, p=0.02) and transapical approach (β −0.22, p<0.001).ConclusionsThe measurement of EP-SVi is useful to assess the immediate haemodynamic benefit of TAVR and to predict the risk of late mortality.

We sought to determine the prognostic value of qualitative and quantitative analysis obtained by real-time myocardial perfusion echocardiography (RTMPE) in patients with known or suspected coronary artery disease (CAD). Quantification of myocardial blood flow reserve (MBFR) in patients with CAD using RTMPE has been demonstrated to further improve accuracy over the analysis of wall motion (WM) and qualitative analysis of myocardial perfusion (QMP). From March 2003 to December 2008, we prospectively studied 168 patients with normal left ventricular function (LVF) who underwent dobutamine stress RTMPE. The replenishment velocity reserve (β) and MBFR were derived from RTMPE. Acute coronary events were: cardiac death, myocardial infarction and unstable angina with need for urgent coronary revascularization. During a median follow-up of 34 months (5 days to 6.9 years), 17 acute coronary events occurred. Abnormal β reserve in ≥2 coronary territories was the only independent predictor of events hazard ratio (HR) = 21, 95% CI = 4.5-99; p<0.001). Both, abnormal β reserve and MBFR added significant incremental value in predicting events over qualitative analysis of WM and MP (χ2 = 6.6 and χ2 = 24.6, respectively; p = 0.001 and χ2 = 6.6 and χ2 = 15.5, respectively; p = 0.012, respectively). When coronary angiographic data was added to the multivariate analysis model, β reserve remained the only predictor of events with HR of 21.0 (95% CI = 4.5-99); p<0.001. Quantitative dobutamine stress RTMPE provides incremental prognostic information over clinical variables, qualitative analysis of WM and MP, and coronary angiography in predicting acute coronary events.

BackgroundLeft ventricular global longitudinal strain (LVLS) is a powerful predictor of outcome in patients with low-flow, low-gradient aortic stenosis (LF-LG AS) and low LV ejection fraction (LVEF). However, the impact of right ventricular (RV) function on the outcome of these patients remains unknown.ObjectivesThe aim of this study was to examine the impact of RV function as evaluated by RV free wall longitudinal strain (RVLS) on mortality in patients with LF-LG AS and low LVEF.Methods211 patients with LF-LG AS (mean gradient <40 mm Hg and indexed aortic valve area (AVA) ≤0.6 cm2/m2) and low LVEF (≤40%)) were prospectively recruited in the True or Pseudo-severe Aortic Stenosis study. AS severity was assessed using the projected AVA (AVAproj) at normal flow rate. Among the 211 patients, 128 had RVLS measurement available at rest and were included in this analysis. RVLS measurement at dobutamine stress echocardiography (DSE) was available in 58 of the 128 patients.ResultsTwo-year survival was lower in patients with RVLS<|13|% (53%±9%) compared with those with RVLS>|13|% (69%±5%) (p=0.04). In multivariable Cox analysis stratified for the type of treatment (aortic valve replacement vs conservative) and adjusted for age, AS severity, previous myocardial infarction and LVLS, rest RVLS<|13|% (HR=2.70; 95% CI 1.19 to 6.11; p=0.018) was independently associated with all-cause mortality. RVLS had incremental prognostic value over baseline risk factors and LVLS (χ2=20.13 vs 13.56; p=0.01). Reduced stress RVLS was also associated with increased risk of mortality (stress RVLS<|14|%: HR=2.98; 95% CI 1.30 to 6.52; p=0.01). In multivariable Cox analysis, stress RVLS<|14|% remained independently associated with mortality (HR=2.94; 95% CI 1.23 to 7.02; p=0.015). After further adjustment for rest RVLS, stress RVLS<|14|% remained independently associated with mortality (HR=3.29; 95% CI 1.17 to 9.25; p=0.024), whereas rest RVLS was not (p>0.05).ConclusionsIn this series of patients with LF-LG AS and low LVEF, reduced RVLS was independently associated with increased risk of mortality. Furthermore, stress RVLS provided incremental prognostic value beyond that obtained from rest RVLS. Thus, RVLS measurement at rest and at DSE may be helpful to enhance risk stratification in this high-risk population.Trial registration numberNCT01835028; Results.

[...]many studies found that some single risk factors were superior to the multifactorial surgical risk scores for the prediction of poor outcomes among TAVI candidates. 9 The inclusion of a high proportion of octogenarians in TAVI studies, who were highly underrepresented in the cohorts used for the development of such surgical risk scores, and the limited data on the discriminatory and calibration power within this zone of (higher) risk have been argued as important reasons for the low prediction capacity of such scores. 10-13 Table 2 Study Endpoint No. of patients Type of score Discrimination C-statistic (AUC) D'Ascenzo et al 10 30-day mortality 962 Logistic EuroSCORE 0.53 STS-PROM 0.62 Hemmann et al 11 30-day mortality 426 Logistic EuroSCORE 0.64 STS-PROM 0.68 EuroSCORE II 0.64 Stahli et al 12 30-day mortality 350 Logistic EuroSCORE 0.61 STS-PROM 0.59 EuroSCORE II 0.70 Watanabe et al 13 30-day mortality 453 Logistic EuroSCORE 0.65 STS-PROM 0.60 EuroSCORE II 0.68 *Only studies with >300 patients selected.