Citations

Background This study aimed to compare percutaneous left atrial appendage occlusion (LAAO) with non‐vitamin K antagonist oral anticoagulants among patients with atrial fibrillation. Methods and Results Using a US administrative database, 562 850 patients with atrial fibrillation were identified, among whom 8397 were treated with LAAO and 554 453 were treated with non‐vitamin K antagonist oral anticoagulants between March 13, 2015 and December 31, 2018. Propensity score overlap weighting was used to balance baseline characteristics. The primary outcome was a composite end point of ischemic stroke or systemic embolism, major bleeding, and all‐cause mortality. The mean age was 76.4±7.6 years; 280 097 (49.8%) were female. Mean follow‐up was 1.5±1.0 years. LAAO was associated with no significant difference in the risk of the primary composite end point (hazard ratio [HR], 0.93 [0.84–1.03]), or the secondary outcomes including ischemic stroke/systemic embolism (HR, 1.07 [0.81–1.41]), and intracranial bleeding (HR, 1.08 [0.72–1.61]). LAAO was associated with a higher risk of major bleeding (HR, 1.22 [1.05–1.42], P =0.01) and a lower risk of mortality (HR, 0.73 [0.64–0.84], P <0.001). The lower risk of mortality associated with LAAO was most pronounced in patients with a prior history of intracranial bleeding. Conclusions In comparison to non‐vitamin K antagonist oral anticoagulants, LAAO was associated with no significant difference in the risk of the composite outcome and a lower risk of mortality, which suggests LAAO might be a reasonable option in select patients with atrial fibrillation. The observation of higher bleeding risk associated with LAAO highlights the need to optimize postprocedural antithrombotic regimens as well as systematic efforts to assess and address bleeding predispositions.

Background Despite improvements in the management and prevention of stroke, increasing hospitalizations for stroke and stagnant mortality rates have been described in young adults. However, there is a paucity of contemporary national mortality estimates in young adults. Methods and Results Trends in mortality related to stroke in young adults (aged 25–64 years) were assessed using the Centers for Disease Control and Prevention Wide‐Ranging Online Data for Epidemiologic Research database. Age‐adjusted mortality rates per 100 000 people with associated annual percentage change were calculated. Joinpoint regression was used to assess the trends in the overall sample and different demographic (sex, race and ethnicity, and age) and geographical (state, urban‐rural, and regional) subgroups. Between 1999 and 2019, a total of 566 916 stroke‐related deaths occurred among young adults. After the initial decline in mortality in the overall population, age‐adjusted mortality rate increased from 2013 to 2019 with an associated annual percentage change of 1.5 (95% CI, 1.1–2.0). Mortality rates were higher in men versus women and in non‐Hispanic Black people versus individuals of other races and ethnicities. Non‐Hispanic American Indian or Alaskan Native people had a marked increase in stroke‐related mortality (annual percentage change 2010–2019: 3.3). Furthermore, rural (nonmetropolitan) counties experienced the greatest increase in mortality (annual percentage change 2012–2019: 3.1) compared with urban (metropolitan) counties. Conclusions Following the initial decline in stroke‐related mortality, young adults have experienced increasing mortality rates from 2013 to 2019, with considerable differences across demographic groups and regions.

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P &amp;lt; .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P &amp;lt; .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P &amp;lt; .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

Background: Transcatheter aortic valve replacement (TAVR) is now an approved alternative to surgical aortic valve replacement for the treatment of severe aortic stenosis. As the clinical adoption of TAVR expands, it remains important to identify predictors of mortality after TAVR. We aimed to evaluate the impact of sex differences in aortic valve calcium score (AVCS) on long-term mortality following TAVR in a large patient sample. Methods: We included consecutive patients who successfully underwent TAVR for treatment of severe native aortic valve stenosis from June 2010 to May 2021 across all US Mayo Clinic sites with follow-up through July 2021. AVCS values were obtained from preoperative computed tomography of the chest. Additional clinical data were abstracted from medical records. Kaplan-Meier curves and Cox-proportional hazard regression models were employed to evaluate the effect of AVCS on long-term mortality. Results: A total of 2543 patients were evaluated in the final analysis. Forty-one percent were women, median age was 82 years (Q1: 76, Q3: 86), 18.4% received a permanent pacemaker following TAVR, and 88.5% received a balloon expandable valve. We demonstrate an increase in mortality risk with higher AVCS after multivariable adjustment ( P <0.001). When stratified by sex, every 500-unit increase in AVCS was associated with a 7% increase in mortality risk among women (adjusted hazard ratio, 1.07 [95% CI, 1.02–1.12]) but not in men. Conclusions: We demonstrate a notable sex difference in the association between AVCS and long-term mortality in a large TAVR patient sample. This study highlights the potential value of AVCS in preprocedural risk stratification, specifically among women undergoing TAVR. Additional studies are needed to validate this finding.

Abstract Aims There are several risk scores designed to predict mortality in patients with heart failure (HF). This study aimed to assess performance of risk scores validated for mortality prediction in patients with acute HF (AHF) and chronic HF. Methods and results MEDLINE and Scopus were searched from January 2015 to January 2021 for studies which internally or externally validated risk models for predicting all-cause mortality in patients with AHF and chronic HF. Discrimination data were analysed using C-statistics, and pooled using generic inverse-variance random-effects model. Nineteen studies (n = 494 156 patients; AHF: 24 762; chronic HF mid-term mortality: 62 000; chronic HF long-term mortality: 452 097) and 11 risk scores were included. Overall, discrimination of risk scores was good across the three subgroups: AHF mortality [C-statistic: 0.76 (0.68–0.83)], chronic HF mid-term mortality [1 year; C-statistic: 0.74 (0.68–0.79)], and chronic HF long-term mortality [≥2 years; C-statistic: 0.71 (0.69–0.73)]. MEESSI-AHF [C-statistic: 0.81 (0.80–0.83)] and MARKER-HF [C-statistic: 0.85 (0.80–0.89)] had an excellent discrimination for AHF and chronic HF mid-term mortality, respectively, whereas MECKI had good discrimination [C-statistic: 0.78 (0.73–0.83)] for chronic HF long-term mortality relative to other models. Overall, risk scores predicting short-term mortality in patients with AHF did not have evidence of poor calibration (Hosmer–Lemeshow P &gt; 0.05). However, risk models predicting mid-term and long-term mortality in patients with chronic HF varied in calibration performance. Conclusions The majority of recently validated risk scores showed good discrimination for mortality in patients with HF. MEESSI-AHF demonstrated excellent discrimination in patients with AHF, and MARKER-HF and MECKI displayed an excellent discrimination in patients with chronic HF. However, modest reporting of calibration and lack of head-to-head comparisons in same populations warrant future studies.

Background: Previous percutaneous coronary intervention risk models were focused on single outcome, such as mortality or bleeding, etc, limiting their applicability. Our objective was to develop contemporary percutaneous coronary intervention risk models that not only determine in-hospital mortality but also predict postprocedure bleeding, acute kidney injury, and stroke from a common set of variables. Methods: We built risk models using logistic regression from first percutaneous coronary intervention for any indication per patient (n=19 322, 70.6% with acute coronary syndrome) using the Mayo Clinic registry from January 1, 2000 to December 31, 2016. Approval for the current study was obtained from the Mayo Foundation Institutional Review Board. Patients with missing outcomes (n=4183) and those under 18 (n=10) were removed resulting in a sample of 15 129. We built both models that included procedural and angiographic variables (Models A) and precatheterization model (Models B). Results: Death, bleeding, acute kidney injury, and stroke occurred in 247 (1.6%), 650 (4.3%), 1184 (7.8%), and 67 (0.4%), respectively. The C statistics from the test dataset for models A were 0.92, 0.70, 0.77, and 0.71 and for models B were 0.90, 0.67, 0.76, and 0.71 for in-hospital death, bleeding, acute kidney injury, and stroke, respectively. Bootstrap analysis indicated that the models were not overfit to the available dataset. The probabilities estimated from the models matched the observed data well, as indicated by the calibration curves. The models were robust across many subgroups, including women, elderly, acute coronary syndrome, cardiogenic shock, and diabetes. Conclusions: The new risk scoring models based on precatheterization variables and models including procedural and angiographic variables accurately predict in-hospital mortality, bleeding, acute kidney injury, and stroke. The ease of its application will provide useful prognostic and therapeutic information to both patients and physicians.

AbstractBackgroundMitral transcatheter edge‐to‐edge repair (MTEER) is an established therapeutic approach for mitral regurgitation (MR). Functional mitral regurgitation originating from atrial myopathy (A‐FMR) has been described.ObjectivesWe sought to assess the clinical, echocardiographic and hemodynamic considerations in A‐FMR patients undergoing MTEER.MethodsFrom 2014 to 2020, patients undergoing MTEER for degenerative MR (DMR), functional MR (FMR), and mixed MR were assessed. A‐FMR was defined by the presence of MR > moderate in severity; left ventricular (LV) ejection fraction (LVEF) ≥ 50%; and severe left atrial (LA) enlargement in the absence of LV dysfunction, leaflet pathology, or LV tethering. The diagnosis of A‐FMR (vs. ventricular‐FMR [V‐FMR]) was confirmed by three independent echocardiographers. Baseline characteristics, procedural outcomes as well as clinical and echocardiographic follow‐up are reported. Device success was defined as final MR grade ≤ moderate; MR reduction ≥1 grade; and final transmitral gradient <5 mmHg.Results306 patients underwent MTEER, including DMR (62%), FMR (19%), and mixed MR (19%). FMR cases included 37 (63.8%) V‐FMR and 21 (36.2%) A‐FMR. Tricuspid regurgitation (≥ moderate) was higher in A‐FMR (80.1%) compared to V‐FMR (54%) and DMR (42%). Device success did not significantly differ between A‐FMR and V‐FMR (57% vs. 73%, p = 0.34) or DMR (57% vs. 64%, p = 1.0). The A‐FMR cohort was less likely to achieve ≥3 grades of MR reduction compared to V‐FMR (19% vs. 54%, p = 0.01) and DMR (19% vs. 49.7%, p = 0.01). Patients with V‐FMR and DMR demonstrated significant reductions in mean left atrial pressure (LAP) and peak LA V‐wave, though A‐FMR did not (LAP −0.24 ± 4.9, p = 0.83; peak V‐wave −1.76 ± 9.1, p = 0.39). In follow‐up, echocardiographic and clinical outcomes were similar.ConclusionsIn patients undergoing MTEER, A‐FMR represents one‐third of FMR cases. A‐FMR demonstrates similar procedural success but blunted acute hemodynamic responses compared with DMR and V‐FMR following MTEER. Dedicated studies specifically considering A‐FMR are needed to discern the optimal therapeutic approaches.

In the evaluation of embolic strokes of undetermined source, great emphasis is often placed on cardiovascular disease, namely on atrial fibrillation. Other pathophysiologic mechanisms, however, may also be involved. Carotid artery intraplaque hemorrhage (IPH)—the presence of blood components within an atheromatous plaque—has become increasingly recognized as a possible etiologic mechanism in some cryptogenic strokes. IPH is a marker of plaque instability and is associated with ipsilateral neurologic ischemic events, even in nonstenotic carotid plaques. As recognition of carotid IPH as an etiology of embolic strokes has grown, so too has the complexity with which such patients are evaluated and treated, particularly because overlaps exist in the risk factors for atrial fibrillation and IPH. In this article, we review what is currently known about carotid IPH and how this clinical entity should be approached in the context of the evaluation of embolic strokes of undetermined source.

Introduction: Unsupervised machine learning (ML) can provide insight into a dataset without significant expert time for annotation and labeling, but was never used to assess the heterogeneous MitraClip population. Hypothesis: We hypothesized that unsupervised k-means ML could identify prognostically-distinct phenogroups in MitraClip patients without a priori knowledge of the dataset. Methods: Patients who underwent MitraClip (June 2014-September 2020) at Mayo Clinic sites were identified from the Mayo institutional NCDR database for baseline and follow-up data. Variables with ≥ 50% missing data were excluded. A k-means algorithm was used for clustering analysis. Input variables were grouped according to 4 distinct k-means determined clusters. Kaplan-Meier survival analysis was used to assess the survival of each cluster. Results: A total of 389 consecutive patients were included in the final analysis, and 95 unique variables were used. The mean age was 80.3±8.7 years; 256 (65.8%) were male. The mean STS MV Replace score was 9.1±5.7. Fifty-five (14.5%) patients died during the mean follow duration (185 days). Kaplan-Meier analysis showed significant survival differences among clusters (Figure 1). The cluster (cluster 2, n=120) with best survival performance (all-cause mortality 3.3%) had features of non-calcified mitral leaflets, nonischemic cardiomyopathy, and less than moderate tricuspid regurgitation. Cluster 3 (n=66) had the worst survival performance (all-cause mortality 27.3%) and opposite features than cluster 2. Conclusions: Unsupervised ML can identify distinct phenotype clusters with prognostic significance in MitraClip patients. Patients with non-calcified mitral leaflets, nonischemic cardiomyopathy, and less than moderate tricuspid regurgitation are intrinsically different from other MitraClip patients and should be considered the potential optimal candidates.