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Background: Comparative data between self-expanding Navitor (NAV) and balloon-expandable SAPIEN 3 Ultra (ULTRA) transcatheter heart valves (THVs) in patients with small aortic annuli are lacking.

Aims: This study sought to evaluate outcomes of transcatheter aortic valve implantation (TAVI) using the intra-annular NAV and the ULTRA THVs in severe aortic stenosis patients with small annuli.

Methods: Patients with an aortic annulus area ≤430 mm² undergoing TAVI with either NAV or ULTRA from the NAVULTRA registry were included. Propensity-matched analysis was performed for adjustment. Primary endpoints included 1-year mortality, a composite endpoint (all-cause mortality, disabling stroke, or heart failure hospitalisation), and 30-day device-oriented outcomes (severe prosthesis-patient mismatch, moderate or greater paravalvular leak [PVL], mean gradient ≥20 mmHg).

Results: Among 1,617 patients, 524 propensity score-matched pairs were analysed. At 1 year, all-cause mortality was 8.8% with NAV versus 9.0% with ULTRA (adjusted p=0.585), and the composite endpoint occurred in 11.3% versus 11.8%, respectively (adjusted p=0.149). The device-oriented endpoint favoured NAV compared to ULTRA (6.0% vs 29.3%; adjusted p<0.01), with a lower residual transvalvular gradient (7.3 mmHg vs 12.7 mmHg; adjusted p<0.01), and reduced incidence of any prosthesis-patient mismatch (odds ratio 0.27, 95% confidence interval: 0.18-0.43; adjusted p<0.01). However, NAV was associated with higher rates of mild paravalvular leak (NAV 33.5% vs ULTRA 23.2%; adjusted p<0.05) and permanent pacemaker implantation (PPI; NAV 20.1% vs 11.9% ULTRA; adjusted p<0.01).

Conclusions: In patients with small aortic annuli, TAVI with both NAV and ULTRA provided comparable 1-year clinical outcomes, but NAV showed better haemodynamic performance at the cost of higher rates of mild PVL and PPI.

Background Frailty and female sex are both recognised independent predictors of adverse outcomes after acute myocardial infarction (AMI). While females presenting with AMI are known to have a higher burden of frailty than males, it is unknown whether this fully explains sex-based disparities in outcomes, or if the prognostic impact of frailty itself differs between the sexes. Methods We conducted a retrospective national cohort study using data from the Myocardial Ischaemia National Audit Project (MINAP), linked to hospital admission and mortality registries in England and Wales between 2005 and 2019. Frailty was assessed using the Secondary Care Administrative Records Frailty (SCARF) index and categorised as fit, mild, moderate, or severe. Multivariable Cox proportional hazards models were used with a primary outcome of all-cause mortality at 1-year. Findings Of 931,133 patients with AMI, 317,967 (34.1%) were female. Frailty was more prevalent in females than in males (severe frailty: 53,065 [16.7%] vs. 64,018 [10.4%]). Males received more intensive therapeutic care across all frailty levels. After multivariable adjustment, the relationship between severe frailty and 1-year all-cause mortality was 26% greater in males than in females (relative hazard ratio [rHR]: 1.26, 95% CI 1.19-1.32, P-interaction <0.001). This corresponded to an adjusted absolute risk difference of 1.19% (95% CI 0.58%-1.79%) Interpretation In this national AMI cohort, while frailty was more prevalent in females, its association with 1-year mortality was significantly greater in males. This sex-specific effect of frailty challenges current risk-assessment paradigms and underscores the need for sex-informed care pathways.

Background

Immunoglobulin light chain (AL) amyloidosis is a well-recognized complication of multiple myeloma (MM), with important prognostic implications. However, the effect of cardiac AL amyloidosis on survival in MM patients has been rarely investigated.

Objective

We aimed to perform a systematic review and meta-analysis to quantitatively assess the prognosis of MM patients with and without concomitant cardiac AL amyloidosis.

Methods

We searched PubMed, Scopus and Cochrane databases for studies comparing the survival of MM patients with and without concomitant cardiac AL amyloidosis. The primary outcome was all-cause mortality at 12 months (short-term), while secondary outcomes included all-cause mortality at 24 and 36 months (long-term). We also reconstructed individual patient data (IPD) from Kaplan–Meier curves to estimate Restricted Mean Survival Time (RMST). We pooled risk ratios (RR) with 95% confidence intervals (CI) using a random-effects model.

Results

We included five studies encompassing 272 patients, of whom 110 (40%) presented MM with concomitant cardiac AL amyloidosis. All-cause mortality at 12 months was nearly five times higher in MM patients with cardiac involvement compared to those without cardiac involvement (RR 4.25; 95% CI 1.99–9.04; p = 0.0002). This trend remained consistent at long-term follow-up, with increased mortality observed in patients with cardiac involvement at 24 months (RR 1.84; 95% CI 1.19–2.84; p = 0.006) and 36 months (RR 1.78; 95% CI 1.26–2.52; p = 0.001. RMST was 27.28 months shorter in patients with cardiac involvement (p < 0.0001).

Conclusion

These finding show that Cardiac AL amyloidosis is a major determinant of survival in MM patients. These findings should be interpreted in the context of the moderate risk of bias and heterogeneity of the available observational evidence.

The level of evidence (LOE) grading system for ESC Clinical Practice Guidelines classifies the quality of the evidence supporting a recommendation. However, the current taxonomy does not fully consider the optimal study design necessary to establish evidence for such recommendations. Therefore, two separate taskforces of clinical and methodological experts were appointed by the Clinical Practice Guidelines Committee, with the first tasked with updating the LOE grading system for therapy and prevention, and the second responsible for developing a LOE grading system for diagnosis and prediction. The updated system for therapy and prevention presented here maintains the three-level grading structure but uses revised definitions. Level of evidence A represents conclusive evidence usually from ≥2 adequately powered randomized controlled trials (RCTs) free from major bias, with substantial evidence against the play of chance when combined in a meta-analysis (e.g. P < .005 for superiority). Additional criteria are specified to define substantial evidence against the play of chance in case of non-inferiority, equivalence, and harm. Level of evidence B is now subdivided into B1 and B2. Level of evidence B1 represents suggestive evidence usually from ≥1 adequately powered RCT free from major bias, or a meta-analysis of such RCTs, with some evidence against the play of chance (e.g. P < .05 for superiority). Level of evidence B2 represents limited evidence from ≥2 adequately powered non-randomized studies with careful control of major sources of bias or from a meta-analysis of small, underpowered RCTs. Level of evidence C represents preliminary evidence from either non-randomized studies without careful control of major sources of bias, a single small, underpowered RCT, or expert consensus.

Randomized controlled trials (RCTs) are the cornerstone of modern evidence-based medicine. They are considered essential to establish definitive evidence of efficacy and safety for new drugs, and whenever possible they should also be the preferred method for investigating new high-risk medical devices. Well-designed studies robustly inform clinical practice guidelines and decision-making, but administrative obstacles have made it increasingly difficult to conduct informative RCTs. The obstacles are compounded for RCTs of high-risk medical devices by extra costs related to the interventional procedure that is needed to implant the device, challenges with willingness to randomize patients throughout a trial, and difficulties in ensuring proper blinding even with sham procedures. One strategy that may help is to promote the wider use of simpler and more streamlined RCTs using data that are collected routinely during healthcare delivery. Recent large simple RCTs have successfully compared the performance of drugs and of high-risk medical devices, against alternative treatments; they enrolled many patients in a short time, limited costs, and improved efficiency, while also achieving major impact. From a task conducted within the CORE-MD project, we report from our combined experience of designing and conducting large pharmaceutical trials during the COVID-19 pandemic, and of planning and coordinating large registry-based RCTs of cardiovascular devices. We summarize the essential principles and utility of large simple RCTs, likely applicable to all interventions but especially in order to promote their wider adoption to evaluate new medical devices.

Before a high-risk medical device is approved for implantation into patients, there should be evidence not only of performance and safety with a favourable benefit-risk ratio, but also of its clinical efficacy. Regulatory guidance on study methodologies is lacking, however, so the European Commission funded the CORE-MD project (Coordinating Research and Evidence for Medical Devices) to advise regulators on appropriate designs for clinical trials of high-risk devices. The CORE-MD consortium recommends that evaluation should be planned in four stages. Randomised controlled trials should be performed more often, against active comparators reflecting the best available treatment, using sham interventions with ethical safeguards. Large trials can be managed efficiently using an electronic database or registry. Non-randomised clinical studies can apply objective performance criteria or other validated patient relevant outcome measures, with adjustments to minimise bias. Full transparency of results from clinical investigations is essential. Proportionate regulation of breakthrough or orphan devices for independently-defined serious unmet needs may involve approval with less evidence, but on condition of subsequent confirmatory studies. These CORE-MD consensus proposals have been submitted to European Union medical device regulators, to be considered as a basis for more transparent and predictable requirements for clinical evidence. 

BACKGROUND

Randomized trials support angiographic and physiology-guided complete revascularization (CR) vs incomplete revascularization (IR) in ST-segment elevation myocardial infarction (STEMI) with multivessel disease (MVD). The implementation of these strategies in clinical practice is uncertain.

OBJECTIVES

In patients undergoing percutaneous coronary intervention for STEMI with MVD, we assessed temporal trends in the utilization of different revascularization strategies and associated outcomes.

METHODS

We included 20,131 patients from the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) registry who underwent primary percutaneous coronary intervention for STEMI with MVD between 2009 and 2021. Primary outcome was a composite of all-cause mortality, myocardial infarction, or unplanned revascularization, landmarked at 90 days postindex to account for staged procedures during this time. RESULTS We observed increased adoption of CR (2009: 33% [n = 397 of 1,217]; 2015: 46% [n = 767 of 1,658]; 2021: 51% [n = 816 of 1,603]; P-trend <0.001) and physiology-guided CR (2009: 0% [n = 0 of 1,217]; 2015: 7% [n = 119 of 1,658]; 2021: 14% [n = 218 of 1,603]; P-trend < 0.001). Over a median follow-up of 4.2 years (Q1-Q3: 1.8-7.1 years), the adjusted risk of a primary event was lower with angiographic CR vs IR (adjusted HR [aHR]: 0.84, 95% CI: 0.79-0.89) and physiology-guided CR vs IR (aHR: 0.80, 95% CI: 0.69-0.93) but not physiology-guided CR vs angiographic CR (aHR: 0.94, 95% CI: 0.80-1.11).

CONCLUSIONS

In patients with STEMI and MVD, the implementation of CR and physiology-guided procedures increased over time. As of 2021, 51% of patients underwent CR and 14% physiology-guided CR. CR, whether angiographically or physiology guided, was independently associated with favorable outcomes, including mortality. (JACC Cardiovasc Interv. 2025;18:1246-1259) (c) 2025 Published by Elsevier on behalf of the American College of Cardiology Foundation.

Background: In recent years, transcatheter aortic valve implantation (TAVI) has rapidly emerged as a key treatment option for aortic stenosis. TAVI has been performed at Uppsala University Hospital since 2009. Data on TAVI procedures have been collected in a nation-wide all-comer registry, the Swedish Transcatheter Cardiac Intervention Registry (SWENTRY). However, only limited analysis has been conducted on trends in short- and long-term outcomes of TAVI patients in Sweden.

Methods: This registry-based cohort study aims to evaluate outcome trends and long-term prognosis in patients who underwent TAVI in a Swedish single center between 2009 and 2023. Survival outcomes were studied using the Kaplan-Meier method. Cox Proportional Hazards models were used to adjust for differences in patient characteristics over time.

Results: In total, 1,741 TAVI procedures were performed between 2009 and 2023. Immediate procedural mortality and 1-year mortality averaged at 0.9 and 8.1%, respectively. Both procedural and long-term mortality showed a decreasing trend over time. Similar results were observed when controlling for comorbidities and age.

Conclusions: Short-term outcomes and long-term prognosis have been constantly improving for patients undergoing TAVI within this study. Similar mortality and complication trends have been observed in other registry studies. These trends may be attributed to improvements in the quality of care, and the increased use of TAVI in lower risk patients.

BACKGROUND: No comparative data exist with the self-expanding Navitor (NAV) and the balloon-expandable SAPIEN 3 Ultra (ULTRA) transcatheter heart valves (THVs).

OBJECTIVES: This study sought to investigate the 1-year outcomes of transcatheter aortic valve replacement using the intra-annular NAV and the ULTRA THVs.

METHODS: The NAVULTRA (Navitor and SAPIEN 3 Ultra) registry included consecutive patients who underwent transfemoral transcatheter aortic valve replacement at 16 centers with NAV or ULTRA between November 2018 and April 2024. Propensity score matching was used for adjustment. The primary outcomes of interest were all-cause death and the composite of all-cause death, disabling stroke, and hospitalization for heart failure at 1 year.

RESULTS: The overall study cohort included 3,878 patients treated with NAV (n = 1,746) or ULTRA (n = 2,176). The propensity score-matched population resulted in 1,363 pairs. At 1 year, the rate of death from any cause was 9.7% with NAV and 9.9% with ULTRA (adjusted P = 0.585). Similarly, there were no significant differences in primary composite outcome (13.6% in the NAV group and 12.6% in the ULTRA group; adjusted P = 0.218). The rate of new permanent pacemaker implantation (20.6% vs 10.6%; adjusted P < 0.01) and heart failure rehospitalization (4.6% vs 2.8%; adjusted P < 0.05) was higher in NAV group. At 1 year, the use of NAV was associated with higher rates of mild paravalvular leak (OR: 1.53; 95% CI: 1.01 to 2.33; adjusted P < 0.05) but lower mean transprosthetic gradients compared with ULTRA (mean change:-3.90, 95% CI: -4.47 to -3.34; adjusted P < 0.01).

CONCLUSIONS: Both intra-annular THVs were associated with similar 1-year clinical outcomes; however, differences were observed in secondary clinical endpoints and valve hemodynamic performance.