Atrial fibrillation (AF) is associated with a high risk of stroke, as well as cognitive decline and dementia. Advanced imaging techniques were employed to test the hypothesis that AF worsens cerebrovascular function as evaluated using neurovascular coupling (NVC) and cerebrovascular carbon dioxide reactivity (CVRCO2) tests. Twenty healthy controls (HC; 63.4 ± 9.5 years) and 19 AF patients (66.6 ± 12.0 years) completed NVC (visual stimulation with a flickering checkerboard) and CVRCO2 (5%CO2) assessments during functional (blood oxygen level-dependent [BOLD]) and perfusion (arterial spin labelling) magnetic resonance imaging. Additionally, brain volumes and cognition were assessed. During CVRCO2 assessment, neither %∆ in BOLD signal (HC: 3.09 ± 0.50; AF: 3.23 ± 0.70%; p = 0.513) nor %∆ in cerebral blood flow (CBF) (HC: 36.6 ± 18.8; AF: 43.6 ± 20.6%; p = 0.319) were different between groups. During NVC assessment, CMRO2 (HC: 5.25 ± 1.84; AF: 4.36 ± 2.50%, p = 0.285), %∆BOLD (HC: 1.60 ± 0.38; AF: 1.66 ± 0.79%; p = 0.762) and %∆CBF (HC: 49.4 [20.1-71.9]; AF: 51.7 [38.3-66.9]%; p = 0.850) all increased similarly in HC and AF. AF patients had lower hippocampal volume relative to total intracranial volume than HC (0.50 ± 0.06 vs 0.55 ± 0.06%; p = 0.020). There were no differences between HC and AF in cognitive performance across multiple domains (all p > 0.05). These results suggest that NVC and CVRCO2 responses are preserved in AF.

Importance As transcatheter aortic valve replacement (TAVR) is considered for younger and lower-risk populations, the durability of bioprosthetic valves is increasingly important. Limited data exist on long-term (7 years and beyond) valve durability. Objective To report 7-year valve durability outcomes for low-risk patients with symptomatic severe aortic stenosis treated with TAVR vs surgery. Design, Setting, and Participants Between March 2016 and October 2017, a total of 1000 patients were enrolled at 71 centers in the US and Canada and randomized to undergo TAVR vs surgery. The patient population for the present analysis consisted of all patients who underwent valve implantation (495 with TAVR and 453 with surgery). The last 7-year follow-up occurred in March 2025. Interventions Patients were randomized to balloon-expandable TAVR with the SAPIEN 3 valve or surgery with any commercially available valve. Main Outcomes and Measures The main outcomes of this analysis were stage 2 or 3 bioprosthetic valve dysfunction (BVD) related to structural valve deterioration (SVD), thrombosis, or endocarditis; all-cause bioprosthetic valve failure (BVF); BVF related to SVD; and aortic valve reintervention at 7 years. Analyses are presented as cumulative incidence rates with death as a competing risk. Results The mean (SD) age of the study population was 73.5 (6.0) years, and 657 participants (69.3%) were male. Of 671 patients who were still alive and enrolled in the study at 7-year follow-up, 537 (80.0%) were available for echocardiographic analysis. Cumulative incidence rates of stage 2 or 3 SVD-related BVD (7.3% vs 7.6%; hazard ratio [HR], 0.96; 95% CI, 0.59-1.57; P = .88), all-cause BVF (6.9% vs 7.5%; HR, 0.91; 95% CI, 0.55-1.49; P = .69), SVD-related BVF (3.9% vs 5.3%; HR, 0.72; 95% CI, 0.39-1.36; P = .31), and valve reintervention (6.0% vs 5.5%; HR, 1.09; 95% CI, 0.62-1.90; P = .77) were low and similar for TAVR and surgery, respectively. Stage 2 or 3 thrombosis-related BVD (subclinical and clinical) occurred more frequently with TAVR (5.2% vs 0.9%; HR, 5.52; 95% CI, 1.92-15.85; P < .001), although most events occurred within 3 years and few progressed to BVF. Rates of stage 2 or 3 endocarditis-related BVD were also low and similar (0.4% in the TAVR group vs 0.5% in the surgery group; HR, 0.85; 95% CI, 0.12-6.07; P = .87). The proportion of patients alive and free of all-cause BVF was 73.4% (331/451) with TAVR vs 74.8% (288/385) with surgery ( P = .69). Conclusions and Relevance In this ad hoc analysis of a randomized clinical trial among low-risk patients with symptomatic severe aortic stenosis randomized to TAVR or surgery, both TAVR and surgery demonstrated comparable and sustained valve durability, with low and similar rates of SVD, all-cause BVF, and reintervention through 7 years. These findings may inform discussions of valve replacement strategies. Trial Registration ClinicalTrials.gov Identifier: NCT02675114

Background:The impact of early nonfatal complications on subsequent mortality and quality of life (QOL) after contemporary transcatheter aortic valve implantation (TAVI) remains unclear. Methods:This post-hoc substudy of the LANDMARK trial included patients with severe aortic stenosis randomized to the Myval transcatheter heart valve (THV) series or to contemporary THV (Sapien or Evolut) series. Early nonfatal complications were defined as events occurring within 30 days after TAVI in patients surviving the first 30 days and included stroke, type 3 bleeding, major vascular complications, acute kidney injury stages 2-4, moderate or severe aortic regurgitation, new permanent pacemaker implantation, or reintervention according to the VARC-3 early safety endpoint. The primary endpoint was all-cause mortality from 30 to 365 days. QOL was assessed using the Short Form-12 at baseline, 30 days, and 1 year. Results:Of the 768 randomized patients, 742 were alive at 30 days. Of these, 177 (23.9%) experienced at least 1 early nonfatal complication, whereas 565 (76.1%) did not. Age (80 ± 5 years vs. 80 ± 6 years, p = 0.67) and Society of Thoracic Surgeons score (median 2.6 [interquartile range: 1.6-3.9] vs. 2.6 [1.7-3.9], p = 0.76) were similar between groups. Patients with early nonfatal complications had higher mortality between 30 and 365 days (8.0% vs. 3.9%, p = 0.03). Early nonfatal complications were independently associated with increased 1-year mortality (hazard ratio = 2.14; 95% CI, 1.07-4.27; p = 0.03). One-year QOL did not differ between groups. Conclusions:In this post-hoc, hypothesis-generating analysis, early nonfatal complications after TAVI were associated with increased 1-year mortality, whereas 1-year QOL was comparable among survivors; findings should be interpreted with caution due to potential survivor bias. Trial registration number:ClinicalTrials.gov, NCT04275726.

BACKGROUND:Conduction system disturbances resulting in permanent pacemaker implantation (PPI) are common complications after transcatheter aortic valve implantation (TAVI). In some patients, there is delayed recovery of the conduction system post-procedure. This study aims to report the incidence and predictors of ventricular pacing (VP) rate≦1% at 1 year after TAVI. METHODS:This is a post-hoc sub-study of the LANDMARK multicentre trial, which randomized 768 patients in a 2:1:1 ratio to the Myval (n = 384) transcatheter heart valve (THV) series or contemporary THVs (Sapien [n = 192] and Evolut [n = 192] series) for the treatment of severe aortic stenosis. Overall, 122 (15.9%) patients underwent PPI within 30 days after TAVI, and 1-year pacemaker follow-up data were retrospectively collected in 99 patients. Pacemaker recovery (PMR) was defined as a VP rate ≦1% at follow-up. RESULTS:PMR occurred in 18% (18/99) of patients. The PMR group was younger than the non-PMR group (78.6 ± 3.0 vs 81.1 ± 5.1 years, p = 0.045). Implantation depth under the non-coronary cusp did not differ between groups (5.7 ± 3.5 vs 5.8 ± 2.8 mm, p = 0.94). There were no significant differences in PMR rates based on THV type: Myval 25% (11/44), Sapien 19% (5/27), and Evolut 7% (2/28) (p = 0.16). In multivariable logistic regression, atrial fibrillation was associated with lower odds of PMR (odds ratio 0.09, 95% confidence interval 0.00-0.77, p = 0.02. CONCLUSIONS:At 1 year, conduction system recovery (VP≦1%) was observed in 18% of patients who underwent PPI after TAVI, with no significant difference among the Myval, Sapien and Evolut series. Atrial fibrillation was associated with lower odds of recovery.

BACKGROUND:Double kissing crush (DKC) is a preferred two-stent technique for complex coronary bifurcation lesions. Proximal cell rewiring is routinely recommended to reduce technical failure, and DKC is considered effective across various bifurcation angles. However, it remains unclear whether this standard approach is optimal for all patients. AIMS:This study investigates the interaction between bifurcation angle and rewiring configuration to identify anatomy-specific strategies. METHODS:Computational modeling of the DKC procedure was used to simulate 12 DKC procedures across three left main bifurcation angles (45°, 70°, and 100°) and four rewiring configurations: proximal-proximal (P-P), proximal-distal (P-D), distal-proximal (D-P), and distal-distal (D-D). Evaluation metrics included stent malapposition, side branch ostium clearance, arterial wall stress, low time-averaged endothelial shear stress, and high shear rates. RESULTS:DKC performed in wide bifurcations (100°) resulted in worse outcomes, with malapposition reaching 18%, side branch clearance down to 23%, and up to twice the exposure to adverse high shear rates compared to narrower angles. In contrast, intermediate (70°) and narrow (45°) angles generally resulted in more favorable outcomes, though optimal rewiring varied by angle. Proximal strategies, that is, P-P and P-D, were most effective at 70°, while D-D performed best at 45°. No single strategy was consistently superior across all bifurcation angles. CONCLUSIONS:DKC outcomes depend on bifurcation angle and can be optimized by tailoring rewiring strategies, challenging the current clinical understanding. These findings support anatomy-specific procedural planning and intravascular imaging to guide rewiring. This study provides a mechanistic rationale to improve clinical decision-making and tailor bifurcation interventions.

Background Stent underexpansion is a key determinant to both short- and long-term outcomes after percutaneous coronary intervention (PCI). Current strategies available have inherent limitations in the setting of stent underexpansion, and intravascular lithotripsy (IVL) remains off-label for in-stent use. Our study aimed to demonstrate the safety and efficacy of IVL use in underexpanded stents. Methods We undertook a retrospective analysis of PCIs involving IVL at 3 centers in New Zealand between September 2018 and November 2023. We identified cases in which IVL was utilized for both old and new in-stent lesions. The primary outcome was a 12-month major adverse cardiac events (cardiac death, nonfatal myocardial infarction [MI], or ischemia-driven target vessel revascularization [ID-TVR]). Secondary outcomes were procedural success (<30% residual stenosis), 30-day cardiac and noncardiac death, nonfatal MI, ID-TVR, and stent thrombosis. Angiographic and intravascular imaging outcomes were also analyzed. Results Between September 2018 and November 2023, 68 of 743 IVL cases involved in-stent lesions. Of the cases, 69% were acute coronary syndrome presentations. Twelve-month major adverse cardiac events were 8.8%. Procedural success was 87%. At 30 days, there was 1 noncardiac death but no cardiac death, nonfatal MI, ID-TVR, or stent thrombosis events. Serious complications included 2 cases of slow flow. Angiographic mean minimal lumen diameter pre-PCI was 0.89 ± 0.54 mm, post-IVL was 2.40 ± 0.60 mm, and post-stenting was 3.01 ± 0.69 mm. Intravascular imaging use was 41%; mean minimal lumen area was 3.60 ±1.78 mm2 pre-PCI and 8.71 ± 3.28 mm2 post-PCI. Conclusions Our multicenter retrospective analysis demonstrates that IVL is a safe and effective tool in the treatment of underexpanded stents with 12-month MACE rates comparable to those of de novo coronary lesions and a high rate of procedural success. Larger, randomized studies are required to elucidate the optimal approach for treating underexpanded stents.

BACKGROUND:A 72-year-old patient presented with breathlessness and presyncope due to severe stenosis within a 25-mm Perimount bioprosthetic aortic valve. The patient had hepatic cirrhosis and was not a candidate for redo surgical valve replacement. A computed tomography transcatheter aortic valve implantation (TAVI) demonstrated severe aorto-ostial left main calcific disease, with dense calcification from the annulus to the inferior border of the left main ostium, which was thought to represent a retained native leaflet, with high risk of coronary obstruction. CASE SUMMARY:Using cerebral protection, rotational atherectomy was undertaken through the aorto-ostial calcification and retained leaflet, followed by left main stem percutaneous coronary intervention. A staged TAVI with a 23-mm Sapien S3 and a chimney stent for coronary protection was successful. DISCUSSION:Although concomitant left main stem rotational atherectomy and TAVI have been described, no reports of rotablation to facilitate leaflet modification have been identified. TAKE-HOME MESSAGE:Rotational atherectomy helped to modify the retained aortic valve leaflet and safely facilitate TAVI in a nonsurgical candidate.

BACKGROUND: There are limited head-to-head randomised trials comparing the performance of different transcatheter heart valves (THVs). AIMS: We aimed to evaluate the non-inferiority of the balloon-expandable Myval THV series compared to the balloon-expandable SAPIEN THV series or the self-expanding Evolut THV series. METHODS: The LANDMARK trial randomised 768 patients in a 1:1 ratio, (Myval THV series [n=384] vs contemporary series with 50% SAPIEN THV series [n=192] and 50% Evolut THV series [n=192]). The non- inferiority of Myval over the SAPIEN or Evolut THV series in terms of the 30-day primary composite safety and effectiveness endpoint as per the third Valve Academic Research Consortium (VARC-3) was tested in an intention- to-treat population with a predefined statistical power of 80% (1-sided alpha of 5%) for a non-inferiority margin of 10.44%. RESULTS: The Myval THV series achieved non-inferiority for the primary composite endpoint over the SAPIEN THV series (24.7% vs 24.1%, risk difference [95% confidence interval {CI}]: 0.6% [not applicable {NA} to 8.0]; p=0.0033) and the Evolut THV series (24.7% vs 30.0%, risk difference [95% CI]: -5.3% [NA to 2.5]; p<0.0001). The incidences of pacemaker implantation were comparable (Myval THV series: 15.0%, SAPIEN THV series: 17.3%, Evolut THV series: 16.8%). At 30 days, the mean pressure gradient and effective orifice area were significantly better with the Myval THV series compared to the SAPIEN THV series (p<0.0001) and better with the Evolut THV series than with the Myval THV series (p<0.0001). At 30 days, the proportion of moderate to severe prosthetic valve regurgitation was numerically higher with the Evolut THV series compared to the Myval THV series (7.4% vs 3.4%; p=0.06), while not significantly different between the Myval THV series and the SAPIEN THV series (3.4% vs 1.6%; p=0.32). CONCLUSIONS: The Myval THV series is non-inferior to the SAPIEN THV series and the Evolut THV series in terms of the primary composite endpoint at 30 days. Clinical trial registration: ClinicalTrials.gov: NCT04275726; EudraCT number 2020-000,137-40.

BACKGROUND:In the LANDMARK trial, the Myval balloon-expandable transcatheter heart valve (THV) series was noninferior to the most commonly used contemporary SAPIEN and Evolut Series THVs for the 30-day early safety endpoint in participants with symptomatic severe native aortic stenosis. OBJECTIVES:The current report from the LANDMARK trial describes clinical outcomes, hemodynamic performances, and quality of life at 1 year. METHODS:This open-label, noninferiority trial enrolled 768 participants across 31 hospitals in Europe, New Zealand, and Brazil. Participants were randomly assigned (1:1) to receive either a Myval THV series or a contemporary THV (SAPIEN or Evolut series). The composite endpoint at 1 year included all-cause mortality, all strokes, and procedure- or valve-related hospitalizations. Clinical efficacy was defined as freedom from the composite endpoint. As recommended in Valve Academic Research Consortium-3, the previous composite endpoint combined with the assessment of quality of life at baseline and 1 year with the 12-Item Short Form Health Survey was reported as an extended composite endpoint. The noninferiority hypothesis was prespecified for the assessment of the primary endpoint at 30 days. Considering the specific 1-year composite endpoints of Valve Academic Research Consortium-3 and the event rate of 27.23% derived from recent studies, an a posteriori descriptive and exploratory noninferiority hypothesis was introduced with a noninferiority margin of 10.89%. The analysis was performed in the intention-to-treat population. RESULTS:The mean age was 80 years, 48% were women, and the median Society of Thoracic Surgeons Predicted Risk of Mortality score was 2.6%. There was no significant difference in the Kaplan-Meier estimates of freedom from the composite endpoint at 365 days (Myval THV 87.0% vs contemporary THVs 86.9%). The Myval THV series was noninferior to the contemporary THVs for the composite endpoint (difference: -0.1%; 1-sided 95% CI: 3.9%; Pnoninferiority < 0.0001). Similarly, there were no significant differences in freedom from the extended composite endpoint (80.5% vs 77.3%; difference: 3.2%; 95% CI: -2.9% to 9.2%; P = 0.33). CONCLUSIONS:In the treatment of symptomatic severe native aortic stenosis, the clinical and hemodynamic outcomes of the Myval THV series were comparable to those of contemporary THVs for the 1-year composite of all-cause mortality, all strokes, or procedure- or valve-related hospitalizations. (LANDMARK Trial: a Randomised Controlled Trial of Myval THV [LANDMARK]; NCT04275726).

Coronary anatomy governs local haemodynamics associated with atherosclerotic development, progression and ultimately adverse clinical outcomes. However, lack of large sample size studies and methods to link adverse haemodynamics to anatomical information has hindered meaningful insights to date. The Left Main coronary bifurcations of 127 patients with suspected coronary artery disease in the absence of significant stenosis were segmented from CTCA images before computing the local haemodynamics. We correlated 11 coronary anatomical characteristics with the normalised lumen area exposed to adverse haemodynamics linked with atherosclerotic processes. These include mean curvatures and diameters of branches, bifurcation and inflow angles, and Finet's ratio as the anatomical parameters, and low Time-Averaged Endothelial Shear Stress ( lowTAESS < 0.5 Pa), high Oscillatory Shear Index (highOSI > 0.1), high Relative Residence Time (highRRT > 4.17 Pa-1), and mean Topological Shear Variation Index for the haemodynamics consideration. We separately tested if the geometric measures and haemodynamics indicators differed between subgroups (sex, smokers, and those with hypertension). We then use a step-down multiple linear regression model to find the best model for predicting lowTAESS, highOSI, highRRT and meanTSVI. Finet's Ratio (FR) significantly correlated to lowTAESS ( p < 0.001 ). Vessel diameters and curvature correlated to highOSI (both p < 0.001) as well as meanTSVI (p < 0.05). Finet's ratio, vessel diameters and daughter branch curvature independently correlated to RRT (all p < 0.01). Our results indicate that specific anatomical vessel characteristics may be used as a surrogate of adverse haemodynamics environment associated with clinically adverse mechanisms of disease. This is especially powerful with the latest computing resources and may unlock clinical integration via standard imaging modalities as biomarkers without further computationally expensive simulations.

BACKGROUND The sirolimus-eluting bioadaptor is a novel coronary implant that unlocks, separates, and maintains dynamic support of the vessel at the lesion site 6 months after percutaneous coronary intervention when the polymer coating covering the helical strands resorbs. This enables the bioadaptor to maintain the established flow lumen and to restore hemodynamic modulation of the artery, including cyclic pulsatility, vasomotion, and adaptive remodeling. OBJECTIVES The purpose of this study was to report the first randomized clinical evidence of the DynamX bioadaptor implant through 2 years compared with the Resolute Onyx contemporary drug-eluting stent. METHODS This multicenter, single-blind, 1:1 randomized clinical trial was conducted at 34 hospitals in Japan, Europe, and New Zealand. The eligibility criterion was de novo coronary lesions in up to 2 vessels. The sample size was based on the primary endpoint, noninferiority of 12-month target lesion failure (TLF). The authors herein report 2-year outcomes. RESULTS In total, 445 patients were enrolled; 3 patients treated for in-stent restenosis and 2 who did not receive the assigned study device because of randomization error were excluded from the analysis. In the per-protocol population of patients with de novo native coronary lesions treated with the assigned device (n = 440), 2-year Kaplan-Meier estimates of TLF and target vessel failure rates in the bioadaptor group were lower (1.8% [4 of 219] vs 5.5% [12 of 221], risk difference-3.6% [95% CI:-7.8% to-0.0%; P = 0.044], and 1.8% [4 of 219] vs 5.9% (13 of 221), risk difference-4.1% [95% CI:-7.2% to-1.0%; P = 0.027], respectively). One clinically driven target lesion revascularization occurred between 6 months and 2 years in the bioadaptor group, whereas 2 cardiovascular deaths and 4 clinically driven target lesion revascularizations occurred in the drug-eluting stent group. The 2-year rate of definite or probable device thrombosis was 0.0% vs 0.5% (n = 1) (P = 0.32), respectively. CONCLUSIONS This is the first report of 2-year outcomes comparing the bioadaptor implant with a contemporary drug-eluting stent. At 2-year follow-up, fewer TLF events were observed in patients treated with the bioadaptor. (The Elixir Bioadaptor vs. the Onyx Stent in De Novo Native Coronary Arteries [BIOADAPTOR RCT]; NCT04192747) (JACC Cardiovasc Interv. 2025;18:988-997) (c) 2025 Published by Elsevier on behalf of the American College of Cardiology Foundation.

Objective: Studies have shown marked sex disparities in Coronary Artery Diseases (CAD) epidemiology, yet the underlying mechanisms remain unclear. We explored the coronary anatomy and the resulting haemodynamics in patients with suspected but no significant CAD. Left Main (LM) bifurcations were 3D-reconstructed from 127 Computed Tomography Angiography images (42 males and 85 females, aged 38-81). Methods: Shape parameters including bifurcation angles, curvature, and diameters were measured, before solving the clinically relevant haemodynamic metrics. The severity and location of the vascular area exposed to adverse haemodynamics were compared between sexes. Results: Females were more likely than males to exhibit adversely low Time Averaged Endothelial Shear Stress (TAESS) along the inner wall of a bifurcation (16.8% vs. 10.7%). Males had a higher percentage of areas exposed to both adversely high Relative Residence Time (6.1% vs 4.2%, p = 0.001) and high Oscillatory Shear Index OSI (4.6% vs 2.3%, p<0.001). However, the OSI values were generally small and should be interpreted cautiously. Males had larger arteries (M vs F, LM: 4.0±0.5mm vs 3.3±0.6mm, LAD: 3.6±0.5mm vs 3.0±0.5mm, LCX:3.5±0.5mm vs 2.9±0.6mm), and females exhibited higher curvatures in all three branches (M vs F, LM: 0.40 vs 0.46, LAD: 0.45 vs 0.51, LCx: 0.47 vs 0.55,p<0.001). There was no difference in bifurcation angles. Conclusion: These differences may in part contribute to differences in CAD risk between sexes. Significance: This work facilitates a better understanding of sex differences in factors contributing to CAD, ultimately improving screening and therapeutic strategies particularly for women who currently have worse predictive outcomes.