Stroke; A Journal Of Cerebral Circulation[JOURNAL]
Sun
200 papers
Efficacy and Safety of Edoxaban in Anticoagulant Therapy Early After Surgical Bioprosthetic Valve Replacement: A Randomized Clinical Trial.
Izumi C, Amano M, Yoshikawa Y … +14 more , Fukushima S, Yaku H, Eishi K, Sakaguchi T, Ohno N, Hiraoka A, Okada K, Saiki Y, Miura T, Komiya T, Minami M, Yamamoto H, Omae K, ENBALV Trial Investigators
Circ Cardiovasc Interv · 2025 Jul · PMID 40663622 · Publisher ↗
BACKGROUND: Anticoagulant therapy with vitamin K antagonists is recommended in the current guidelines for 3 to 6 months following bioprosthetic valve replacement. However, in the era of direct oral anticoagulants, there...
BACKGROUND: Anticoagulant therapy with vitamin K antagonists is recommended in the current guidelines for 3 to 6 months following bioprosthetic valve replacement. However, in the era of direct oral anticoagulants, there is a paucity of evidence regarding the efficacy and safety of direct oral anticoagulants in this patient group. METHODS: The ENBALV trial (Edoxaban in Anticoagulant Therapy After Surgical Bioprosthetic Valve Replacement) was an investigator-initiated, phase 3, randomized, open-label, multicenter study that aimed to evaluate the efficacy and safety of edoxaban compared with warfarin within 3 months following bioprosthetic valve replacement at the aortic or mitral position or both. The primary outcome was stroke or systemic embolism. The secondary outcomes included major bleeding, intracardiac thrombus, and a composite of stroke, systemic embolism, or major bleeding. Given the limited study period and the low event rate of the primary outcome, this study assessed the difference in the point estimates of the event rate. RESULTS: Of the 410 enrolled patients, 389 were included in the final analysis (73±6 years, 56.8% male, 79.4% sinus rhythm; edoxaban group: n=195, warfarin group: n=194). The primary outcome occurred in 0.5% (n=1) in the edoxaban group, whereas in 1.5% (n=3) in the warfarin group (risk difference, -1.03% [95% CI, -4.34 to 1.95%]). Major bleeding occurred in 4.1% (n=8) in the edoxaban group and in 1.0% (n=2) in the warfarin group (risk difference, 3.07% [95% CI, -0.67 to 7.27%]). No fatal bleeding or intracranial hemorrhage was observed in patients treated with edoxaban, whereas 1 fatal intracranial hemorrhage occurred in the warfarin group. Intracardiac thrombus did not occur in any of the patients in the edoxaban group, but did occur in 1.0% (n=2) in the warfarin group. CONCLUSIONS: Edoxaban is a potential alternative anticoagulant therapy early after bioprosthetic valve replacement. REGISTRATION: URL: https://jrct.niph.go.jp/latest-detail/jRCT2051210209; Unique identifier: jRCT2051210209.
Association Between Automated Coronary Artery Calcium From Routine Chest Computed Tomography Scans and Cardiovascular Risk in Patients With Colorectal or Gastric Cancer.
Kim S, Kim S, Cha MJ … +5 more , Kim HS, Kim HS, Hyung WJ, Cho I, You SC
Circ Cardiovasc Qual Outcomes · 2025 Jul · PMID 40519001 · Publisher ↗
BACKGROUND: As cardiovascular disease (CVD) is the leading cause of noncancer mortality in colorectal or gastric cancer patients, it is essential to identify patients at increased CVD risk. Coronary artery calcium (CAC)...
BACKGROUND: As cardiovascular disease (CVD) is the leading cause of noncancer mortality in colorectal or gastric cancer patients, it is essential to identify patients at increased CVD risk. Coronary artery calcium (CAC) is an established predictor of atherosclerotic CVD; however, its application is limited in this population. This study evaluates the association between automated CAC scoring using chest computed tomography and atherosclerotic CVD risk in colorectal or gastric cancer patients. METHODS: A retrospective cohort study was conducted using electronic health records linked to claims data of colorectal or gastric cancer patients who underwent non-ECG-gated chest computed tomography at 2 tertiary hospitals in South Korea between 2011 and 2019. CAC was automatically quantified using deep learning software and used to classify patients into 4 groups (CAC=0, 0<CAC≤100, 100<CAC≤400, CAC>400). The primary outcome was major adverse cardiovascular events (myocardial infarction, stroke, or cardiovascular mortality), and assessed using the multivariable Fine and Gray subdistribution hazard model. A meta-analysis was performed to calculate pooled subdistribution hazard ratios. RESULTS: A total of 3153 patients were included in this study (36.5% women; 36.3% CAC=0; 38.1% 0<CAC≤100; 14.1% 100<CAC≤400; 11.5% CAC>400). The mean follow-up period was 4.1 years. The incidence rate of MACE was 5.28, 8.03, 9.99, and 29.14 per 1000 person-years in CAC=0, 0<CAC≤100, 100<CAC≤400, and CAC>400. Compared with CAC=0, the risk of MACE was not significantly different in patients with 0<CAC≤100 (subdistribution hazard ratio, 1.43 [95% CI, 0.41-5.01]), and 100<CAC≤400 (subdistribution hazard ratio, 0.99 [95% CI, 0.48-2.04]). Patients with CAC>400 had 2.33 (95% CI, 1.24-4.39) times higher risk of MACE compared with those with CAC=0. CONCLUSIONS: CAC>400 was associated with an increased risk of MACE compared with CAC=0 among colorectal or gastric cancer patients. CAC quantified on routine chest computed tomography scans provides prognostic information for atherosclerotic CVD risk in this population.
Cardiac Biomarkers in Patients With Asymptomatic Severe Aortic Stenosis: Analysis From the EARLY TAVR Trial.
Lindman BR, Pibarot P, Schwartz A … +27 more , Oldemeyer JB, Su YR, Goel K, Cohen DJ, Fearon WF, Babaliaros V, Daniels D, Chhatriwalla A, Suradi HS, Shah P, Szerlip M, Mack MJ, Dahle T, O'Neill WW, Davidson CJ, Makkar R, Sheth T, Depta J, DeVries JT, Southard J, Pop A, Sorajja P, Hahn RT, Zhao Y, Leon MB, Généreux P, EARLY TAVR Trial Executive Committee and Study Investigators
Circulation · 2025 Jun · PMID 40163596 · Full text
BACKGROUND: The EARLY TAVR trial (Evaluation of TAVR Compared to Surveillance for Patients With Asymptomatic Severe Aortic Stenosis) demonstrated that early transcatheter aortic valve replacement (TAVR) intervention was...
BACKGROUND: The EARLY TAVR trial (Evaluation of TAVR Compared to Surveillance for Patients With Asymptomatic Severe Aortic Stenosis) demonstrated that early transcatheter aortic valve replacement (TAVR) intervention was superior to clinical surveillance with delayed TAVR in patients with asymptomatic severe aortic stenosis. Cardiac biomarkers are associated with maladaptive remodeling, symptom onset, and worse outcomes after TAVR. Whether elevated biomarkers identify asymptomatic patients more likely to benefit from early intervention is unknown. METHODS: A core laboratory measured NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin T (hs-cTnT) levels. Associations between biomarker levels and risk of the trial primary end point (death, stroke, or unplanned cardiovascular hospitalization) and other secondary end points were examined with Kaplan-Meier curves and Cox proportional hazard models. Interaction tests were performed to assess whether the treatment effect of early TAVR, compared with clinical surveillance, differed according to biomarker levels. RESULTS: Among 901 patients randomized in EARLY TAVR, 798 (89%) had biospecimens measured (median NT-proBNP level, 287 [145, 601]; median hs-cTnT level, 14.6 [10.5, 21.0]). Higher levels of NT-proBNP and hs-cTnT were broadly associated with higher event rates for multiple end points. In general, there was no significant interaction between baseline biomarkers and treatment group with respect to any composite or individual end point examined, although trends broadly demonstrated a greater relative benefit of early TAVR at lower biomarker levels. There was a significant interaction between hs-cTnT level and treatment group with respect to death or heart failure hospitalization ( =0.04) and heart failure hospitalization alone ( =0.03) such that the relative benefit of early TAVR was greater for patients with normal, rather than elevated, levels of hs-cTnT at baseline. For some end points, higher baseline NT-proBNP level was associated with numerically greater absolute risk reduction with early TAVR than were lower NT-proBNP levels. CONCLUSIONS: In patients with asymptomatic severe high-gradient aortic stenosis, higher NT-proBNP and hs-cTnT levels were broadly associated with higher event rates, as expected. However, the relative benefit of an early TAVR strategy was consistent regardless of baseline biomarker levels and, contrary to our hypothesis, tended to be more pronounced in patients with the lowest biomarker levels. These findings suggest limited value for single measurements of these biomarkers to guide the timing of TAVR in asymptomatic patients. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03042104.
Macitentan for Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Pulmonary Vascular Disease: Results of the SERENADE Randomized Clinical Trial and Open-Label Extension Study.
Shah SJ, Bonderman D, Borlaug BA … +6 more , Cleland JGF, Lack G, Lu W, Voors AA, Zannad F, Gladwin MT
Circ Heart Fail · 2025 Mar · PMID 40066571 · Full text
BACKGROUND: Despite favorable hemodynamic and neurohormonal effects, endothelin receptor antagonists have not improved outcomes in patients with heart failure (HF), possibly because they cause fluid retention. METHODS: I...
BACKGROUND: Despite favorable hemodynamic and neurohormonal effects, endothelin receptor antagonists have not improved outcomes in patients with heart failure (HF), possibly because they cause fluid retention. METHODS: In this randomized, double-blind, multicenter trial (SERENADE [Macitentan in Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease]), we evaluated the effects of an endothelin receptor antagonist, macitentan, in patients with HF, left ventricular ejection fraction ≥40%, and pulmonary vascular disease. After a 4-week placebo run-in (to ensure clinical stability), followed by a 5-week single-blind macitentan run-in, patients who did not exhibit fluid retention were randomized to macitentan or placebo. The primary end point was change in NT-proBNP (N-terminal pro-B-type natriuretic peptide; baseline to 24 weeks); secondary end points included change in KCCQ (Kansas City Cardiomyopathy Questionnaire) clinical summary score (baseline to 24 weeks) and time to worsening HF by 52 weeks. RESULTS: Of 230 patients enrolled, 28 were excluded during the placebo run-in, 60 excluded during the macitentan run-in, and 142 were randomized. Macitentan had no effect on change in NT-proBNP (geometric mean ratio [macitentan/placebo], 1.02 [90% CI, 0.88-1.19]; =0.79) or on secondary end points (placebo-corrected change in KCCQ clinical summary score, -3.5 [90% CI, -8.2 to +1.2]; =0.22). Worsening HF occurred in 20 (28%) patients assigned to macitentan and 13 (18%) assigned to placebo (hazard ratio, 1.48 [90% CI, 0.83-2.67]; =0.24). More macitentan-treated patients developed fluid retention (16 [23%] versus 10 [14%]) and cardiac adverse events (33 [46%] versus 22 [31%]) versus placebo. CONCLUSIONS: Despite a novel enrichment trial design to target pulmonary vascular disease and exclude treatment-related fluid retention in patients with HF and preserved/mildly reduced left ventricular ejection fraction, macitentan neither lowered NT-proBNP nor improved HF outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03153111 and NCT03714815.
Harnessing the Plasma Proteome to Predict Mortality in Heart Failure Subpopulations.
Chadwick J, Hinterberg MA, Asselbergs FW … +18 more , Biegel H, Boersma E, Cappola TP, Chirinos JA, Coresh J, Ganz P, Gordon DA, Kureshi N, Loupey KM, Orlenko A, Ostroff R, Sampson L, Shrestha S, Sweitzer NK, Williams SA, Zhao L, Kardys I, Lanfear DE
Circ Heart Fail · 2025 Apr · PMID 40052265 · Full text
BACKGROUND: We derived and validated proteomic risk scores (PRSs) for heart failure (HF) prognosis that provide absolute risk estimates for all-cause mortality within 1 year. METHODS: Plasma samples from individuals with...
BACKGROUND: We derived and validated proteomic risk scores (PRSs) for heart failure (HF) prognosis that provide absolute risk estimates for all-cause mortality within 1 year. METHODS: Plasma samples from individuals with HF with reduced ejection fraction (HFrEF; ejection fraction <40%; training/validation n=1247/762) and preserved ejection fraction (HFpEF; ejection fraction ≥50%; training/validation n=725/785) from 3 independent studies were run on the SomaScan Assay measuring ≈5000 proteins. Machine learning techniques resulted in unique 17- and 14-protein models for HFrEF and HFpEF that predict 1-year mortality. Discrimination was assessed via C-index and 1-year area under the curve (AUC), and survival curves were visualized. PRSs were also compared with Meta-Analysis Global Group in Chronic HF (MAGGIC) score and NT-proBNP (N-terminal pro-B-type natriuretic peptide) measurements and further assessed for sensitivity to disease progression in longitudinal samples (HFrEF: n=396; 1107 samples; HFpEF: n=175; 350 samples). RESULTS: In validation, the HFpEF PRS performed significantly better (≤0.1) for mortality prediction (C-index, 0.79; AUC, 0.82) than MAGGIC (C-index, 0.71; AUC, 0.74) and NT-proBNP (PRS C-index, 0.76 and AUC, 0.81 versus NT-proBNP C-index, 0.72 and AUC, 0.76). The HFrEF PRS performed comparably to MAGGIC (PRS C-index, 0.76 and AUC, 0.83 versus MAGGIC C-index, 0.75 and AUC, 0.84) but had a significantly better C-Index (=0.026) than NT-proBNP (PRS C-index, 0.75 and AUC, 0.78 versus NT-proBNP C-index, 0.73 and AUC, 0.77). PRS included known HF pathophysiology biomarkers (93%) and novel proteins (7%). Longitudinal assessment revealed that HFrEF and HFpEF PRSs were higher and increased more over time in individuals who experienced a fatal event during follow-up. CONCLUSIONS: PRSs can provide valid, accurate, and dynamic prognostic estimates for patients with HF. This approach has the potential to improve longitudinal monitoring of patients and facilitate personalized care.
Trajectory of Cognitive Function After Incident Heart Failure.
Shore S, Li H, Zhang M … +19 more , Whitney RT, Gross AL, Bhatt AS, Nallamothu BK, Giordani B, Briceño EM, Sussman JB, Gutierrez J, Yaffe K, Griswold ME, Johansen MC, Lopez OL, Gottesman RF, Sidney S, Heckbert SR, Rundek T, Hughes TM, Longstreth WT, Levine DA
Circ Heart Fail · 2025 Mar · PMID 39963777 · Full text
BACKGROUND: The magnitude of cognitive changes after incident heart failure (HF) is unclear. We assessed whether incident HF is associated with changes in cognition after accounting for pre-HF cognitive trajectories and...
BACKGROUND: The magnitude of cognitive changes after incident heart failure (HF) is unclear. We assessed whether incident HF is associated with changes in cognition after accounting for pre-HF cognitive trajectories and known determinants of cognition. METHODS: This pooled cohort study included adults without HF, stroke, or dementia from 6 US population-based studies from 1971 to 2019. Linear mixed-effects models estimated cognitive change with incident HF diagnosis and the rate of cognitive change over the years after HF, controlling for pre-HF cognitive trajectories and participant factors. Outcomes included change in global cognition (primary outcome), executive function, and memory (secondary outcomes). Cognitive outcomes were standardized to a score metric (mean [SD], 50 [10]); a 1-point difference represented a 0.1-SD difference in cognition. RESULTS: We included 29 614 adults (mean [SD] age was 61 [10] years, 55% female, 70% White). During a median follow-up of 6.6 (Q1-Q3, 5.0-19.8) years, 1407 (5%) adults received an incident diagnosis of HF. Incident HF diagnosis was associated with initial decreases in global cognition (-1.1 points [95% CI, -1.4 to -0.8]) and executive function (-0.6 points [95% CI, -1.0 to -0.3]). Larger decreases in global cognition after HF were seen with older age, female sex, and White race. Participants with incident HF diagnosis demonstrated faster and long-term declines in global cognition (-0.1 points per year [95% CI, -0.2 to -0.1]) and executive function (-0.2 points per year [95% CI, -0.2 to -0.1]). The change in memory with incident HF diagnosis was not statistically significant but showed a similar trend with an initial decline of -0.5 points (95% CI, -1.4 to +0.3) and a slope of -0.1 points per year (95% CI, -0.3 to 0.0). CONCLUSIONS: In this pooled cohort study, incident HF diagnosis was associated with initial decreases in global cognition and executive function and faster, persistent declines in these domains at follow-up.
2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.
Martin SS, Aday AW, Allen NB … +39 more , Almarzooq ZI, Anderson CAM, Arora P, Avery CL, Baker-Smith CM, Bansal N, Beaton AZ, Commodore-Mensah Y, Currie ME, Elkind MSV, Fan W, Generoso G, Gibbs BB, Heard DG, Hiremath S, Johansen MC, Kazi DS, Ko D, Leppert MH, Magnani JW, Michos ED, Mussolino ME, Parikh NI, Perman SM, Rezk-Hanna M, Roth GA, Shah NS, Springer MV, St-Onge MP, Thacker EL, Urbut SM, Van Spall HGC, Voeks JH, Whelton SP, Wong ND, Wong SS, Yaffe K, Palaniappan LP, American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Committee
Circulation · 2025 Feb · PMID 39866113 · Full text
BACKGROUND: The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors,...
BACKGROUND: The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The AHA, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2025 AHA Statistical Update is the product of a full year's worth of effort in 2024 by dedicated volunteer clinicians and scientists, committed government professionals, and AHA staff members. This year's edition includes a continued focus on health equity across several key domains and enhanced global data that reflect improved methods and incorporation of ≈3000 new data sources since last year's Statistical Update. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.
Evidence-Based Application of Natriuretic Peptides in the Evaluation of Chronic Heart Failure With Preserved Ejection Fraction in the Ambulatory Outpatient Setting.
Reddy YNV, Tada A, Obokata M … +8 more , Carter RE, Kaye DM, Handoko ML, Andersen MJ, Sharma K, Tedford RJ, Redfield MM, Borlaug BA
Circulation · 2025 Apr · PMID 39840432 · Full text
BACKGROUND: Plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) is commonly used to diagnose heart failure with preserved ejection fraction (HFpEF), but its diagnostic performance in the ambulatory/outpatient se...
BACKGROUND: Plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) is commonly used to diagnose heart failure with preserved ejection fraction (HFpEF), but its diagnostic performance in the ambulatory/outpatient setting is unknown because previous studies lacked objective reference standards. METHODS: Among patients with chronic dyspnea, diagnosis of HFpEF or noncardiac dyspnea was determined conclusively by exercise catheterization in a derivation cohort (n=414), multicenter validation cohort 1 (n=560), validation cohort 2 (n=207), and a nonobese Japanese validation cohort 3 (n=77). Optimal NT-proBNP cut points for HFpEF rule out (optimizing sensitivity) and rule in (optimizing specificity) were derived and tested, stratified by obesity and atrial fibrillation. Derived cut points were tested in 3 additional validation cohorts (cohorts 4-6) in whom HFpEF was diagnosed by resting catheterization only (n=260), previous hospitalization for heart failure (n=447), or exercise echocardiography (n=517), respectively. RESULTS: Current recommended rule-out NT-proBNP threshold <125 pg/mL had 82% sensitivity (95% CI, 77%-88%) with a body mass index (BMI) <35 kg/m, decreasing to 67% (95% CI, 58%-77%) with a BMI ≥35 kg/m. A lower rule-out NT-proBNP threshold <50 pg/mL displayed good sensitivity with a BMI <35 kg/m (97% [95% CI, 95%-99%]), with a modest decline in sensitivity with a BMI ≥35 kg/m (86% [95% CI, 79%-93%]); diagnostic thresholds were confirmed in validation cohorts 1 and 2 (91% [95% CI, 88%-95%] and 86% [95% CI, 80%-93%] with a BMI <35 kg/m; 80% [95% CI, 74%-87%] and 84% [95% CI, 74%-93%] with a BMI ≥35 kg/m). Current consensus age- and BMI-stratified rule-in thresholds demonstrated only 65% specificity (95% CI, 57%-72%). Rule-in NT-proBNP threshold ≥500 pg/mL had 85% specificity (95% CI, 78%-91%) with a BMI <35 kg/m (87% [95% CI, 80%-94%] and 90% [95% CI, 81%-99%] in validation cohorts), with 100% specificity at a BMI ≥35 kg/m (93% [95% CI, 81%-100%] and 100% in validation cohorts). With a BMI ≥35 kg/m, lower rule-in thresholds (≥220 pg/mL) provided good specificity (88% [95% CI, 73%-100%]; 93% [95% CI, 81%-100%] and 100% in validation cohorts). Findings were consistent in validation cohorts 3 through 6 (sensitivity of <50 pg/mL, 93%-98%; specificity of ≥500 pg/mL, 82%-89%). NT-proBNP provided no incremental discrimination among patients with history of AF; ≥98% of patients with AF and dyspnea were found to have HFpEF in our cohorts. CONCLUSIONS: In patients with chronic unexplained dyspnea, current rule-in and rule-out NT-proBNP diagnostic thresholds lead to unacceptably high error rates, with important interactions by obesity and AF status. In our study, NT-proBNP provided little value in those with AF and dyspnea because the presence of AF is by itself a robust biomarker of HFpEF. Use of separate rule-in and rule-out diagnostic thresholds stratified by BMI reduces miscategorization and can guide more appropriate use of exercise testing for possible HFpEF.
Associations of Social, Behavioral, and Clinical Factors With Sex Differences in Stroke Recurrence and Poststroke Mortality.
Chen C, Reeves MJ, He K … +2 more , Morgenstern LB, Lisabeth LD
Circ Cardiovasc Qual Outcomes · 2025 Feb · PMID 39817333 · Full text
BACKGROUND: Few population-based studies have assessed sex differences in stroke recurrence. In addition, contributors to sex differences in recurrence and poststroke mortality, including social factors, are unclear. We...
BACKGROUND: Few population-based studies have assessed sex differences in stroke recurrence. In addition, contributors to sex differences in recurrence and poststroke mortality, including social factors, are unclear. We investigated sex differences in these outcomes and the contribution of social, clinical, and behavioral factors to the sex differences. METHODS: First-ever ischemic stroke cases identified from 2008 to 2019 from the population-based Brain Attack Surveillance in Corpus Christi Project in Texas were included and followed for recurrence and all-cause mortality through 2020. Sex differences in outcomes with and without adjustment for potential confounding factors, including social, behavioral, and clinical factors, were examined using Cox proportional hazard models. Factors that changed the log hazard ratio (HR) for sex by at least 10% after adjustment were identified as confounders/contributors. Final models were adjusted for all identified confounders. RESULTS: Of 2326 participants (mean age, 68 years; 48% women; 57% Mexican American), over median follow-ups of 5.4 years for recurrence and 3.7 years for mortality, 274 recurrences and 965 deaths occurred. No significant sex differences in recurrence were noted in unadjusted (HR, 0.89 [95% CI, 0.70-1.13]), age-adjusted (HR, 0.92 [95% CI, 0.72-1.18]), or fully adjusted models (HR, 0.88 [95% CI, 0.67-1.16]). Although women had a higher crude mortality rate than men (HR, 1.22 [95% CI, 1.08-1.38]), this sex difference disappeared after age adjustment (HR, 0.91 [95% CI, 0.80-1.03]). Other factors contributing to the sex difference included education, marital status, prestroke depression, health behaviors, initial stroke severity, prestroke disability, comorbidities, atrial fibrillation, and coronary artery disease. After simultaneously adjusting for all identified confounders, women had lower poststroke mortality (HR, 0.79 [95% CI, 0.68-0.91]). CONCLUSIONS: Sex differences in stroke recurrence were not apparent. Women had a higher unadjusted poststroke mortality rate but lower adjusted mortality than men. Social and psychosocial factors, alongside clinical factors, primarily explained the sex disparity in poststroke mortality.
Neutrophil CRACR2A Promotes Neutrophil Recruitment in Sterile Inflammation and Ischemic Stroke.
Lee J, Balzraine B, Schweizer A … +6 more , Kuzmanova V, Gwack Y, Razani B, Lee JM, Mosher DF, Cho J
Circulation · 2025 Mar · PMID 39601147 · Full text
BACKGROUND: Ca release-activated Ca channel regulator 2A (CRACR2A) has been linked to immunodeficiency attributable to T-cell dysfunction in humans. We discovered that neutrophil CRACR2A promotes neutrophil adhesive and...
BACKGROUND: Ca release-activated Ca channel regulator 2A (CRACR2A) has been linked to immunodeficiency attributable to T-cell dysfunction in humans. We discovered that neutrophil CRACR2A promotes neutrophil adhesive and migratory functions by facilitating Ca mobilization and β2 integrin activation. METHODS: Myeloid-specific Cracr2a conditional knockout mice and intravital microscopy were used to investigate the physiologic role of neutrophil Cracr2a in neutrophil recruitment in vascular inflammation. Cracr2a-deficient neutrophils or dHL-60 (differentiated human promyelocytic leukemia) cells and Cracr2a-derived peptides were used in flow cytometry, immunoprecipitation, cytosolic Ca mobilization, and flow chamber assays to elucidate the molecular mechanism. Four-dimensional confocal intravital microscopy of mice after focal brain ischemia and single neutrophil behavioral analysis demonstrated the pathologic role of neutrophil Cracr2a in brain damage. RESULTS: Compared with wild-type control mice, Cracr2a conditional knockout mice exhibited significantly reduced adhesion, crawling, and transmigration of neutrophils on ear and cremaster venules in tumor necrosis factor-α-induced sterile inflammation. Neutrophil Cracr2a rapidly interacts with Stim1 (stromal interaction molecule 1) after agonist stimulation and facilitates Ca mobilization, increasing the ligand-binding function of β2 integrin. Our findings in Cracr2a-deficient mouse neutrophils are recapitulated in dHL-60 cells, in which CRACR2A is deleted by CRISPR/Cas9. Furthermore, overexpression of CRACR2A in CRACR2A KO dHL-60 cells restores normal function. Using a series of peptides covering the coiled-coil region of Cracr2a, we identified a palmitoylated 20-mer that blocks Stim1-Cracr2a interaction. Treating neutrophils with this 20-mer inhibits Ca mobilization and β2 integrin activation after agonist stimulation, reducing neutrophil recruitment to an activated endothelial cell monolayer under venous shear stress and to ear venules in tumor necrosis factor-α-challenged mice. Cerebral 4-dimensional intravital microscopy of mice after focal brain ischemia revealed that neutrophil Cracr2a enhances the emergence of highly migratory neutrophils by increasing the surface level of αMβ2 integrin, thereby facilitating neutrophil infiltration into brain tissue and exacerbating brain injury. CONCLUSIONS: Our results demonstrate that neutrophil CRACR2A promotes neutrophil recruitment to sites of sterile inflammation, such as ischemic stroke. Blocking the STIM1-CRACR2A interaction may be a novel therapeutic strategy to mitigate inflammation and consequent tissue injury.
Clinical Correlates and Prognostic Impact of Cognitive Dysfunction in Patients With Heart Failure and Preserved Ejection Fraction: Insights From PARAGON-HF.
Shen L, Dewan P, Ferreira JP … +20 more , Cunningham JW, Jhund PS, Anand IS, Chandra A, Chiang LM, Claggett B, Desai AS, Gong J, Lam CSP, Lefkowitz MP, Maggioni AP, Martinez F, Packer M, Redfield MM, Rouleau JL, van Veldhuisen DJ, Zannad F, Zile MR, Solomon SD, McMurray JJV
Circulation · 2024 Dec · PMID 39429145 · Publisher ↗
BACKGROUND: Cognitive impairment is common in patients with heart failure and preserved ejection fraction but its clinical correlates and prognostic associations are poorly understood. METHODS: We analyzed cognitive func...
BACKGROUND: Cognitive impairment is common in patients with heart failure and preserved ejection fraction but its clinical correlates and prognostic associations are poorly understood. METHODS: We analyzed cognitive function, using the Mini-Mental State Examination (MMSE), in patients with heart failure and preserved ejection fraction enrolled in a prespecified substudy of the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction). Logistic regression analyses were performed to determine the variables associated with lower MMSE scores at baseline and postbaseline decline in MMSE scores at 48 weeks. Cox proportional hazards regression and semiparametric proportional rates models were used to examine the risk of clinical outcomes related to baseline MMSE scores, and decline in MMSE scores during follow-up, adjusted for prognostic variables including NT-proBNP (N-terminal pro-B-type natriuretic peptide). RESULTS: At baseline, cognitive function was normal (MMSE score 28-30) in 1809 of 2895 patients (62.5%), borderline (score 24-27) in 794 (27.4%), and impaired (score <24) in 292 (10.1%). Variables associated with both a lower MMSE score at baseline and a decline in score from baseline included older age, a history of stroke or transient ischemic attack, and lower serum albumin. Compared with those with baseline MMSE scores of 28 to 30, patients in the lower MMSE score categories had a stepwise increase in the risk of the composite of time to first heart failure hospitalization or cardiovascular death, with an adjusted hazard ratio of 1.27 (95% CI, 1.06-1.53) for those with scores of 24 to 27 and 1.58 (95% CI, 1.21-2.06) for those with scores <24, respectively. These associations were also found for the individual components of the composite and all-cause death. Likewise, cognitive impairment was associated with a 50% higher risk of total (first and repeat) heart failure hospitalizations and cardiovascular deaths. Examining the change in MMSE score from baseline, a decrease in MMSE score during follow-up was associated with a higher risk of death. CONCLUSIONS: In patients with heart failure and preserved ejection fraction, even modest baseline impairment of cognitive function was associated with worse outcomes, including death. A decline in MMSE score during follow-up was a strong predictor of mortality, independent of other prognostic variables.
Clinical Use of Bedside Portable Ultra-Low-Field Brain Magnetic Resonance Imaging in Patients on Extracorporeal Membrane Oxygenation: Results From the Multicenter SAFE MRI ECMO Study.
Cho SM, Khanduja S, Wilcox C … +23 more , Dinh K, Kim J, Kang JK, Chinedozi ID, Darby Z, Acton M, Rando H, Briscoe J, Bush EL, Sair HI, Pitts J, Arlinghaus LR, Wandji AN, Moreno E, Torres G, Akkanti B, Gavito-Higuera J, Keller S, Choi HA, Kim BS, Gusdon A, Whitman GJ, SAFE MRI ECMO Investigators
Circulation · 2024 Dec · PMID 39342513 · Full text
BACKGROUND: Early detection of acute brain injury (ABI) at the bedside is critical in improving survival for patients with extracorporeal membrane oxygenation (ECMO) support. We aimed to examine the safety of ultra-low-f...
BACKGROUND: Early detection of acute brain injury (ABI) at the bedside is critical in improving survival for patients with extracorporeal membrane oxygenation (ECMO) support. We aimed to examine the safety of ultra-low-field (ULF; 0.064-T) portable magnetic resonance imaging (pMRI) in patients undergoing ECMO and to investigate the ABI frequency and types with ULF-pMRI. METHODS: This was a multicenter prospective observational study (SAFE MRI ECMO study [Assessing the Safety and Feasibility of Bedside Portable Low-Field Brain Magnetic Resonance Imaging in Patients on ECMO]; NCT05469139) from 2 tertiary centers (Johns Hopkins, Baltimore, MD and University of Texas-Houston) with specially trained intensive care units. Primary outcomes were safety of ULF-pMRI during ECMO support, defined as completion of ULF-pMRI without significant adverse events. RESULTS: Of 53 eligible patients, 3 were not scanned because of a large head size that did not fit within the head coil. ULF-pMRI was performed in 50 patients (median age, 58 years; 52% male), with 34 patients (68%) on venoarterial ECMO and 16 patients (32%) on venovenous ECMO. Of 34 patients on venoarterial ECMO, 11 (22%) were centrally cannulated and 23 (46%) were peripherally cannulated. In venovenous ECMO, 9 (18%) had single-lumen cannulation and 7 (14%) had double-lumen cannulation. Of 50 patients, adverse events occurred in 3 patients (6%), with 2 minor adverse events (ECMO suction event; transient low ECMO flow) and one serious adverse event (intra-aortic balloon pump malfunction attributable to electrocardiographic artifacts). All images demonstrated discernible intracranial pathologies with good quality. ABI was observed in 22 patients (44%). Ischemic stroke (36%) was the most common type of ABI, followed by intracranial hemorrhage (6%) and hypoxic-ischemic brain injury (4%). Of 18 patients (36%) with both ULF-pMRI and head computed tomography within 24 hours, ABI was observed in 9 patients with a total of 10 events (8 ischemic, 2 hemorrhagic events). Of the 8 ischemic events, pMRI observed all 8, and head computed tomography observed only 4 events. For intracranial hemorrhage, pMRI observed only 1 of them, and head computed tomography observed both (2 events). CONCLUSIONS: Our study demonstrates that ULF-pMRI can be performed in patients on ECMO across different ECMO cannulation strategies in specially trained intensive care units. The incidence of ABI was high, seen in 44% of ULF-pMRI studies. ULF-pMRI imaging appears to be more sensitive to ABI, particularly ischemic stroke, compared with head computed tomography.
Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.
Shaddy R, Burch M, Kantor PF … +38 more , Solar-Yohay S, Garito T, Zhang S, Kocun M, Mao C, Cilliers A, Wang X, Canter C, Rossano J, Wallis G, Menteer J, Daou L, Kusa J, Tokel K, Dilber D, Xu Z, Xiao T, Halnon N, Daly KP, Bock MJ, Zuckerman W, Singh TP, Chakrabarti M, Levitas A, Senni M, Grutter G, Kim GB, Song J, Lee HD, Chen CK, Sanchez-de-Toledo J, Law Y, Wanitkun S, Cui Y, Anjos R, Mese T, Bonnet D, PANORAMA-HF Investigators
Circulation · 2024 Nov · PMID 39319469 · Full text
BACKGROUND: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compar...
BACKGROUND: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD). METHODS: Children with HF attributable to LVSD were randomized to sacubitril/valsartan versus enalapril to assess the efficacy and safety of sacubitril/valsartan at 52 weeks of follow-up. The primary end point of the study was to determine whether sacubitril/valsartan was superior to enalapril for the treatment of pediatric patients with HF attributable to systemic LVSD, assessed using a primary global rank end point consisting of ranking patients from worst to best on the basis of clinical events such as death, listing for urgent heart transplant, mechanical life support requirement, worsening HF, New York Heart Association (NYHA)/Ross class, Patient Global Impression of Severity (PGIS), and Pediatric Quality of Life Inventory physical functioning domain. The change from baseline to 52 weeks in NT-proBNP (N-terminal pro-B-type natriuretic peptide) was an exploratory end point. RESULTS: A total of 375 children (mean age, 8.1±5.6 years; 52% female) were randomized to sacubitril/valsartan (N=187) or enalapril (N=188). At week 52, no significant difference was observed between the 2 treatment arms in the global rank end point (Mann-Whitney probability, 0.52 [95% CI, 0.47-0.58]; Mann-Whitney odds, 0.91 [95% CI, 0.72-1.14]; =0.42). At week 52, clinically meaningful reductions were observed in both treatment arms in NYHA/Ross, PGIS, Patient Global Impression of Change, and NT-proBNP, without significant differences between groups. Adverse events were similar between treatment arms (incidence: sacubitril/valsartan, 88.8%; enalapril, 87.8%), and the safety profile of sacubitril/valsartan was acceptable in children. CONCLUSIONS: In this study, sacubitril/valsartan did not show superiority over enalapril in the treatment of children with HF attributable to systemic LVSD using the prespecified global rank end point. However, both treatment arms showed clinically meaningful improvements over 52 weeks. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02678312.
Effect of Delayed Remote Ischemic Preconditioning on Acute Kidney Injury and Outcomes in Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial.
Jia P, Ji Q, Zou Z … +13 more , Zeng Q, Ren T, Chen W, Yan Z, Shen D, Li Y, Peng F, Su Y, Xu J, Shen B, Luo Z, Wang C, Ding X
Circulation · 2024 Oct · PMID 39319450 · Full text
BACKGROUND: Remote ischemic preconditioning (RIPC) has 2 time windows for organ protection: acute and delayed. Previous studies have mainly focused on the organoprotective effects of acute RIPC. We aimed to determine whe...
BACKGROUND: Remote ischemic preconditioning (RIPC) has 2 time windows for organ protection: acute and delayed. Previous studies have mainly focused on the organoprotective effects of acute RIPC. We aimed to determine whether delayed RIPC can reduce the occurrence of acute kidney injury (AKI) and postoperative complications in patients undergoing cardiac surgery. METHODS: This prospective, single-center, double-blind, randomized controlled trial involved 509 patients at high risk for AKI who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass. Patients were randomized to receive RIPC (4 cycles of 5-minute inflation and 5-minute deflation on 1 upper arm with a blood pressure cuff) 24 hours before surgery or a sham condition (control group) that was induced by 4 cycles of 5-minute inflation to a pressure of 20 mm Hg followed by 5-minute cuff deflation. The primary end point was the incidence of AKI within the prior 7 days after cardiac surgery. The secondary end points included renal replacement therapy during hospitalization, change in urinary biomarkers of AKI and markers of myocardial injury, duration of intensive care unit stay and mechanical ventilation, and occurrence of nonfatal myocardial infarction, stroke, and all-cause mortality by day 90. RESULTS: A total of 509 patients (mean age, 65.2±8.2 years; 348 men [68.4%]) were randomly assigned to the RIPC group (n=254) or control group (n=255). AKI was significantly reduced in the RIPC group compared with the control group (69/254 [27.2%] versus 90/255 [35.3%]; odds ratio, 0.68 [95% CI, 0.47-1.00]; =0.048). There were no significant between-group differences in the secondary end points of perioperative myocardial injury (assessed by the concentrations of cardiac troponin T, creatine kinase myocardial isoenzyme, and NT-proBNP [N-terminal pro-brain natriuretic peptide]), duration of stay in the intensive care unit and hospital, and occurrence of nonfatal myocardial infarction, stroke, and all-cause mortality by day 90. CONCLUSIONS: Among high-risk patients undergoing cardiac surgery, delayed RIPC significantly reduced the occurrence of AKI. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2000035568.
Randomized Invitation to Systematic NT-proBNP and ECG Screening in 75-Year-Olds to Detect Atrial Fibrillation: STROKESTOP II.
Kemp Gudmundsdottir K, Svennberg E, Friberg L … +6 more , Hygrell T, Frykman V, Al-Khalili F, Hijazi Z, Rosenqvist M, Engdahl J
Circulation · 2024 Dec · PMID 39217615 · Publisher ↗
BACKGROUND: Guidelines have suggested screening for atrial fibrillation to enable early treatment and avoid downstream negative clinical events. We aimed to determine whether atrial fibrillation screening potentially enh...
BACKGROUND: Guidelines have suggested screening for atrial fibrillation to enable early treatment and avoid downstream negative clinical events. We aimed to determine whether atrial fibrillation screening potentially enhanced by NT-proBNP (N-terminal pro-B-type natriuretic peptide) would reduce stroke or systemic embolism incidence compared with a control group and to determine whether it was safe for those with low NT-proBNP concentrations to forfeit prolonged screening. METHODS: In this randomized controlled trial, all 75- and 76-year-old individuals in Stockholm Region, Sweden, were randomized 1:1 to be invited to screening or serve as a control group. NT-proBNP concentrations were measured, and a single-lead ECG was registered only once if NT-proBNP <125 ng/L, whereas if NT-proBNP ≥125 ng/L, participants underwent prolonged screening, recording single-lead ECGs 4 times daily for 2 weeks. If atrial fibrillation was detected, treatment was initiated. Baseline and outcome data were collected from Swedish National Registries. RESULTS: In total, 28 712 individuals were randomized. After exclusion of death and emigration, 13 905 remained in the intervention group, 13 884 in the control group. The participation rate in the intervention group was 49.2% (6843 of 13 905). Participants in the high NT-proBNP group (NT-proBNP≥125 ng/L) without previous atrial fibrillation constituted 60% of the total and underwent prolonged screening. New atrial fibrillation was detected in 2.4% (165 of 6843) in the intervention group. There was no difference in atrial fibrillation prevalence or oral anticoagulant treatment between the intervention and the control group after 5 years of follow-up. After a median of 5.1 years (interquartile range, 5.0-5.8), there was no difference in the primary outcome of stroke or systemic embolism between the intervention group and the control group (hazard ratio, 0.96 [95% CI, 0.86-1.06]). The low NT-proBNP group had significantly fewer strokes or systemic emboli than the control group (hazard ratio, 0.59 [95% CI, 0.46-0.74]; <0.001). In the high NT-proBNP group, the risk of stroke or systemic embolism was higher compared with the low NT-proBNP group (hazard ratio, 1.57 [95% CI, 1.22-2.02]; =0.001). CONCLUSIONS: In this population-based screening trial for atrial fibrillation using NT-proBNP for screening enhancement, there was no difference in risk of stroke or systemic embolism for the intervention group compared with controls. Participation was moderate. The use of NT-proBNP for screening enhancement was safe in identifying low-risk participants. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02743416.
Intracranial Atherosclerotic Disease and Incident Dementia: The ARIC Study (Atherosclerosis Risk in Communities).
Zhao D, Guallar E, Qiao Y … +5 more , Knopman DS, Palatino M, Gottesman RF, Mosley TH, Wasserman BA
Circulation · 2024 Sep · PMID 39087353 · Full text
BACKGROUND: Studies of the neurovascular contribution to dementia have largely focused on cerebral small vessel disease (CSVD), but the role of intracranial atherosclerotic disease (ICAD) remains unknown in the general p...
BACKGROUND: Studies of the neurovascular contribution to dementia have largely focused on cerebral small vessel disease (CSVD), but the role of intracranial atherosclerotic disease (ICAD) remains unknown in the general population. The objective of this study was to determine the risk of incident dementia from ICAD after adjusting for CSVD and cardiovascular risk factors in a US community-based cohort. METHODS: We acquired brain magnetic resonance imaging examinations from 2011 through 2013 in 1980 Black and White participants in the ARIC study (Atherosclerosis Risk in Communities), a prospective cohort conducted in 4 US communities. Magnetic resonance imaging examinations included high-resolution vessel wall magnetic resonance imaging and magnetic resonance angiography to identify ICAD. Of these participants, 1590 without dementia, without missing covariates, and with adequate magnetic resonance image quality were followed through 2019 for incident dementia. Associations between ICAD and incident dementia were assessed using Cox proportional hazard ratios adjusted for CSVD (characterized by white matter hyperintensities, lacunar infarctions, and microhemorrhages), APOE4 genotype (apolipoprotein E gene ε4), and cardiovascular risk factors. RESULTS: The mean age (SD) of study participants was 77.4 (5.2) years. ICAD was detected in 34.6% of participants. After a median follow-up of 5.6 years, 286 participants developed dementia. Compared with participants without ICAD, the fully adjusted hazard ratios (95% CIs) for incident dementia in participants with any ICAD, with ICAD only causing stenosis ≤50%, and with ICAD causing stenosis >50% in ≥1 vessel were 1.57 (1.17-2.11), 1.41 (1.02-1.95), and 1.94 (1.32-2.84), respectively. ICAD was associated with dementia even among participants with low white matter hyperintensities burden, a marker of CSVD. CONCLUSIONS: ICAD was associated with an increased risk of incident dementia, independent of CSVD, APOE4 genotype, and cardiovascular risk factors. The increased risk of dementia was evident even among participants with low CSVD burden, a group less likely to be affected by vascular dementia, and in participants with ICAD causing only low-grade stenosis. Our results suggest that ICAD may partially mediate the effect that cardiovascular risk factors have on the brain leading to dementia. Both ICAD and CSVD must be considered to understand the vascular contributions to cognitive decline.
Neurofilament Light Chain and Risk of Stroke in Patients With Atrial Fibrillation.
Aulin J, Sjölin K, Lindbäck J … +8 more , Benz AP, Eikelboom JW, Hijazi Z, Kultima K, Oldgren J, Wallentin L, Burman J, ACTIVE A and AVERROES Investigators
Circulation · 2024 Oct · PMID 39045686 · Publisher ↗
BACKGROUND: Biomarkers reflecting brain injury are not routinely used in risk assessment of stroke in atrial fibrillation (AF). Neurofilament light chain (NFL) is a novel biomarker released into blood after cerebral insu...
BACKGROUND: Biomarkers reflecting brain injury are not routinely used in risk assessment of stroke in atrial fibrillation (AF). Neurofilament light chain (NFL) is a novel biomarker released into blood after cerebral insults. We investigated the association between plasma concentrations of NFL, other biomarkers, and risk of stroke and death in patients with AF not receiving oral anticoagulation. METHODS: For this observational study, baseline plasma samples were available from 3077 patients with AF randomized to aspirin in ACTIVE A (Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events; 2003 to 2008) and AVERROES (Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment; 2007 to 2009). Median follow-up was 1.5 years. NFL was analyzed with a Single Molecule Array (Simoa). Associations with outcomes (total stroke or systemic embolism, ischemic stroke, cardiovascular death, and all-cause death) were explored with Cox regression models. RESULTS: In the combined cohort, the median NFL level was 16.9 ng/L (interquartile range, 11.1-26.5 ng/L), the median age was 71 years, 58% were men, and 13% had a history of previous stroke. NFL was associated with older age, higher creatinine, lower body mass index, previous stroke, female sex, and diabetes but not cardiac rhythm. Higher NFL was associated with a higher risk of stroke or systemic embolism (n=206) independently of clinical characteristics (hazard ratio, 1.27 [95% CI, 1.10-1.46] per doubling of NFL) and other biomarkers (hazard ratio, 1.18 [95% CI, 1.01-1.37]) and including in patients without previous stroke (hazard ratio, 1.23 [95% CI, 1.02-1.48]). NFL was also independently associated with cardiovascular (n=219) and all-cause (n=311) death. The C index for stroke using only NFL was 0.642, on par with the currently used clinical risk scores. Addition of information on NFL improved discrimination in a model also including clinical information, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and high-sensitivity cardiac troponin T, yielding a C index of 0.727. CONCLUSIONS: NFL reflects overt and covert episodes of cerebral ischemia and improves risk assessment of stroke and death in patients with AF without oral anticoagulation, including in patients without previous stroke. The combination of NFL with information on age, history of stroke, and other biomarkers should be explored as a future avenue for stroke risk assessments in patients with AF.
Clinical Outcomes of Percutaneous Transcatheter Release of Stuck Mechanical Mitral Valve With Cerebral Embolic Protection.
Nandhakumar V, Kalidoss L, Ezhilan J … +2 more , Begam S, Ajit MS
Circ Cardiovasc Interv · 2024 Aug · PMID 38853741 · Publisher ↗
BACKGROUND: Surgery or fibrinolysis is the currently available evidence-based treatment for obstructive mechanical valve thrombus. We reported the feasibility and short-term outcomes of percutaneous transcatheter therapy...
BACKGROUND: Surgery or fibrinolysis is the currently available evidence-based treatment for obstructive mechanical valve thrombus. We reported the feasibility and short-term outcomes of percutaneous transcatheter therapy with cerebral embolic protection. Mid- and long-term outcomes remain unknown. METHODS: From 2020 to 2023, 24 patients underwent percutaneous transcatheter release of stuck leaflets with cerebral embolic protection for obstructive mitral mechanical valve thrombus. The indications for the transcatheter therapy were failed fibrinolysis, contraindications for fibrinolysis, not willing for fibrinolysis, or high risk for surgery. The study participants were followed up for a median period of 344.50 (65.00-953.75) days. RESULTS: Technical success was achieved in 91.67% (n=22) of procedures. During the follow-up, 12.50% (n=3) all-cause death, 4.17% (n=1) stroke, and 16.67% (n=4) recurrence were seen. The mean survival time free from death was 1101.48 (95% CI, 929.49-1273.47) days, stroke was 1211.38 (95% CI, 1110.40-1312.35) days, and recurrence was 907.71 (95% CI, 760.20-1055.21) days. CONCLUSIONS: Transcatheter release of the stuck mitral mechanical valve with cerebral embolic protection is an alternative therapy with promising mid-term outcomes where surgery or fibrinolysis is not possible or in failed fibrinolysis subsets.
Prognostic Value of a Multi-mRNA Signature for 1-Year All-Cause Death in Hospitalized Patients With Heart Failure With a Preserved Ejection Fraction.
Gao Y, Chen B, Han Y … +12 more , Lu J, Li X, Tian A, Zhang L, Wang B, Hong Y, Liu J, Li Y, Bilige W, Zhang H, Zheng X, Li J
Circ Heart Fail · 2024 Jun · PMID 38847104 · Publisher ↗
BACKGROUND: Heart failure with preserved ejection fraction is a major global public health problem, while effective risk stratification tools are still lacking. We sought to construct a multi-mRNA signature to predict 1-...
BACKGROUND: Heart failure with preserved ejection fraction is a major global public health problem, while effective risk stratification tools are still lacking. We sought to construct a multi-mRNA signature to predict 1-year all-cause death. METHODS: We selected 30 patients with heart failure with preserved ejection fraction who died during 1-year follow-up and 30 who survived in the discovery set. One hundred seventy-one and 120 patients with heart failure with preserved ejection fraction were randomly selected as a test set and a validation set, respectively. We performed mRNA microarrays in all patients. RESULTS: We constructed a 5-mRNA signature for predicting 1-year all-cause death. The scores of the 5-mRNA signature were significantly associated with the 1-year risk of all-cause death in both the test set (hazard ratio, 2.72 [95% CI, 1.98-3.74]; <0.001) and the validation set (hazard ratio, 3.95 [95% CI, 2.40-6.48]; <0.001). Compared with a reference model, which included sex, ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) score, history of HF and NT-proBNP (N-terminal pro-B-type natriuretic peptide), the 5-mRNA signature had a better discrimination capability, with an increased area under the curve from 0.696 to 0.813 in the test set and from 0.712 to 0.848 in the validation set. A composite model integrating the 5-mRNA risk score and variables in the reference model demonstrated an excellent discrimination capability, with an area under the curve of 0.861 (95% CI, 0.784-0.939) in the test set and an area under the curve of 0.859 (95% CI, 0.755-0.963) in the validation set. The net reclassification improvement and integrated discrimination improvement indicated that the composite model significantly improved patient classification compared with the reference model in both sets (<0.001). CONCLUSIONS: The 5-mRNA signature is a promising predictive tool for 1-year all-cause death and shows improved prognostic power over the established risk scores and NT-proBNP in patients with heart failure with preserved ejection fraction.
Effect of Sacubitril/Valsartan on Cognitive Function in Patients With Heart Failure With Preserved Ejection Fraction: A Prespecified Analysis of PARAGON-HF.
Dewan P, Shen L, Pedro Ferreira J … +19 more , Jhund PS, Anand IS, Chandra A, Chiang LM, Claggett B, Desai AS, Gong J, Lam CSP, Lefkowitz MP, Maggioni AP, Martinez F, Packer M, Redfield MM, Rouleau JL, van Veldhuisen DJ, Zannad F, Zile MR, Solomon SD, McMurray JJV
Circulation · 2024 Jul · PMID 38841854 · Publisher ↗
BACKGROUND: A hypothetical concern has been raised that sacubitril/valsartan might cause cognitive impairment because neprilysin is one of several enzymes degrading amyloid-β peptides in the brain, some of which are neur...
BACKGROUND: A hypothetical concern has been raised that sacubitril/valsartan might cause cognitive impairment because neprilysin is one of several enzymes degrading amyloid-β peptides in the brain, some of which are neurotoxic and linked to Alzheimer-type dementia. To address this, we examined the effect of sacubitril/valsartan compared with valsartan on cognitive function in patients with heart failure with preserved ejection fraction in a prespecified substudy of PARAGON-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction). METHODS: In PARAGON-HF, serial assessment of cognitive function was conducted in a subset of patients with the Mini-Mental State Examination (MMSE; score range, 0-30, with lower scores reflecting worse cognitive function). The prespecified primary analysis of this substudy was the change from baseline in MMSE score at 96 weeks. Other post hoc analyses included cognitive decline (fall in MMSE score of ≥3 points), cognitive impairment (MMSE score <24), or the occurrence of dementia-related adverse events. RESULTS: Among 2895 patients included in the MMSE substudy with baseline MMSE score measured, 1453 patients were assigned to sacubitril/valsartan and 1442 to valsartan. Their mean age was 73 years, and the median follow-up was 32 months. The mean±SD MMSE score at randomization was 27.4±3.0 in the sacubitril/valsartan group, with 10% having an MMSE score <24; the corresponding numbers were nearly identical in the valsartan group. The mean change from baseline to 96 weeks in the sacubitril/valsartan group was -0.05 (SE, 0.07); the corresponding change in the valsartan group was -0.04 (0.07). The mean between-treatment difference at week 96 was -0.01 (95% CI, -0.20 to 0.19; =0.95). Analyses of a ≥3-point decline in MMSE, decrease to a score <24, dementia-related adverse events, and combinations of these showed no difference between sacubitril/valsartan and valsartan. No difference was found in the subgroup of patients tested for apolipoprotein E ε4 allele genotype. CONCLUSIONS: Patients with heart failure with preserved ejection fraction in PARAGON-HF had relatively low baseline MMSE scores. Cognitive change, measured by MMSE, did not differ between treatment with sacubitril/valsartan and treatment with valsartan in patients with heart failure with preserved ejection fraction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe