BACKGROUND: Severe aortic stenosis (AS) is associated with significant morbidity and mortality. Prior reports suggest that severe AS is under-recognized and undertreated. METHODS: Retrospective analysis of the Duke Echoc...BACKGROUND: Severe aortic stenosis (AS) is associated with significant morbidity and mortality. Prior reports suggest that severe AS is under-recognized and undertreated. METHODS: Retrospective analysis of the Duke Echocardiography Laboratory Database of individuals undergoing an echocardiogram between 2016 and 2024. Patients with possible severe AS (any of the following: aortic valve area (AVA) <1.0 cm, mean aortic valve gradient ≥40 mmHg, peak aortic velocity ≥4.0 m/s) and possible low-gradient severe AS (AVA < 1.0 cm, aortic gradient <40 mmHg and peak velocity of <4 m/s) were identified. Individuals were stratified based on stage of cardiac damage. Outcomes of interest included percent of patients receiving appropriate confirmatory testing, aortic valve replacement (AVR), heart failure (HF) hospitalization (total events) and all-cause mortality. RESULTS: Of 114,171 unique individuals who underwent echocardiography, 3,220 had possible severe AS. Those with possible low-gradient severe AS (n = 1,764) infrequently underwent confirmatory testing (18.1% at 1-year). Over a median of 1.4 years of follow-up 1,452 (45.1%) underwent AVR. Significant predictors of AVR utilization included age <75, sex, advanced stage of cardiac damage, absence of symptoms, frailty, ordering provider and severity reported in the echocardiogram. AVR was associated with lower 1-year mortality (hazard ratio 0.46; 95% confidence intervals 0.37-0.57). Overall, the population demonstrated a mortality rate of 17.6 per 100 person-years and a HF hospitalization rate of 13.5 per 100 person-years, which were higher in those with advanced cardiac stages and those with possible low-gradient severe AS. CONCLUSION: Patients with possible severe AS represent a high-risk population with substantial variation in confirmatory testing and AVR utilization, including differences across patient characteristics and provider factors.
BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of respiratory morbidity in adults, particularly among older individuals and those with comorbidities. The DAN-RSV trial was initiated to evaluate bivalent R...BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of respiratory morbidity in adults, particularly among older individuals and those with comorbidities. The DAN-RSV trial was initiated to evaluate bivalent RSV prefusion F (RSVpreF) vaccine effectiveness in preventing RSV-related hospitalizations. METHODS: DAN-RSV is a large-scale, pragmatic, randomized clinical trial that enrolled participants during the 2024/2025 (Danish adults aged ≥60 years) and 2025/2026 (adults aged ≥18 years in Denmark and Galicia, Spain) Northern hemisphere winter seasons. In Denmark, nationwide registries and the national electronic messaging system were used to identify and recruit eligible citizens; individuals could provide electronic informed consent remotely or in-person. In Galicia, participants were recruited via text message invitations and consented on-site. RESULTS: During the initial 2024/2025 season, 131,379 Danish adults aged ≥60 years were enrolled. Following lower-than-expected event accrual and expansion of the EU indication to adults 18 years and older, the trial was extended to continue enrollment of adults aged ≥18 years across Denmark and Galicia, Spain during the 2025/2026 RSV season. Key protocol updates include expansion of the eligibility criteria to adults aged ≥18 years, inclusion of an additional study site within the integrated public healthcare infrastructure of Galicia, Spain, and an increase in the planned sample size to up to approximately 690,000 participants across both seasons. The randomization strategy (1:1 to RSVpreF vaccine or no vaccine), primary endpoint (RSV-related respiratory tract disease hospitalization), and statistical framework, including intention-to-treat analyses and hierarchical testing, remain unchanged. CONCLUSION: The extension of the DAN-RSV trial is expected to improve statistical precision, enhance generalizability, and strengthen the robustness of the effect estimates. The updated design will provide reliable randomized evidence on bivalent RSVpreF vaccine effectiveness to inform clinical and public health decision-making.
D'Ascenzo F, De Filippo O, Pelliccia F
… +39 more, Pasceri V, Dangas G, Mehran R, Porto I, Radico F, Biancari F, Saia F, Luzi G, Bedogni F, Santos IJA, De Marzo V, Dimagli A, Mäkikallio T, Sandrone S, Stabile E, B-Turrión S, Testa L, Barbanti M, Costa G, Fabbiocchi F, Chilmeran A, Stefanini G, Conrotto F, Tamburino C, Spaccarotella C, Cao D, Macchione A, La Torre M, Bendandi F, Wańha W, Wojakowski W, Benedetto U, Indolfi C, Hildick-Smith D, Capodanno D, Miraldi F, Dobrev D, Zimarino M, TRITAVI study group.
BACKGROUND: Patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) are still exposed to a not negligible risk of death during the first year after the procedure, despite a not-compli...BACKGROUND: Patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) are still exposed to a not negligible risk of death during the first year after the procedure, despite a not-complicated procedure. However, few data are still available about timing and kind of death after the procedure. METHODS: Transfusion requirements in transcatheter aortic valve implantation (TRITAVI; NCT03740425) is an international, investigator-initiated registry designed to collect data on patients with symptomatic severe aortic stenosis undergoing TAVI at 18 European sites. The primary end point of the study was all-cause death occurring in patients between 30 days and 1 year without major peri‑procedural complications (major vascular complications, stage 2 to 3 acute kidney injury (AKI) and transfusions) during the procedure. RESULTS: A total of 11,246 patients were included (mean age 82 years; 52% female). Among them, 454 (4%) died between 1 and 12 months without major peri‑procedural complications. Patients who died were also elderly (mean age 82 years) and 50% were female. Of these, 78 (0.7%) died for cardiovascular reasons, while 376 (3.3%) died for noncardiovascular reasons. COPD (HR: 1.35, 95% CI: 1.05-1.73, P = .002), Atrial Fibrillation (HR: 1.46, 95% CI: 1.16-1.84, P = .001), severe Chronic Kidney Disease (CKD) (HR: 1.70, 95% CI: 1.10-2.62, P = .018), moderate and severe reduction of LVEF (respectively HR: 1.42, 95% CI: 1.07-1.90, P = .017 and HR 1.62, 95% CI 1.17-2.23, P = .003) were associated with and increased risk of the primary end point. At competitive risk analysis, risk of non-CV death appeared to be more relevant and to steadily increase across the year, while risk of CV death was lower. Consistently, baseline creatinine (HR: 1.2, 95% CI: 1.1-1.4, P = .002) and AF (HR: 1.4, 95% CI: 1.1-1.8, P = .008) related to increased risk of non-CV death, while higher baseline LVEF related to lower risk (HR: 0.9, 95% CI: 0.8-0.99, P < .001). CONCLUSION: Risk of death between 30 days and 1 year after noncomplicated TAVI is not negligible even for patients without major peri‑procedural complications. It appears mainly driven by non-CV reasons and predicted by baseline renal function, baseline LVEF, and atrial fibrillation.
Costa G, Laterra G, Sammartino S
… +35 more, De Backer O, Jia Y, Pilgrim T, Daijiro T, Montorfano M, Ancona F, Bellini B, Redwood S, Patterson T, Kornowski R, Hamdan A, Mylotte D, Del Sole PA, Saia F, Palmierini T, Bedogni F, Gandolfo C, Cannata S, Garot P, Gall E, De Carlo M, Angelillis M, Immè S, Tamburino C, Mangieri A, Tartaglia F, Nombela L, Santos IA, Gomez MG, Attizzani G, Frazzetto M, Calì M, Millar K, Webb J, Barbanti M
BACKGROUND: Transcatheter aortic valve implantation (TAVI) is now an established and effective alternative to surgery for elderly patients affected by severe aortic stenosis. With the expansion of the indications to youn...BACKGROUND: Transcatheter aortic valve implantation (TAVI) is now an established and effective alternative to surgery for elderly patients affected by severe aortic stenosis. With the expansion of the indications to younger patients, the proportion of patients with bicuspid aortic valve (BAV) undergoing TAVI is expected to increase. Nevertheless, the presence of BAV-associated aortopathy may complicate the transcatheter treatment or it may progress if left untreated. METHODS: The progression of bicuspid-related aortopathy in patients undergoing Transcatheter Aortic Valve Implantation (PROSPERO) registry is an investigator-initiated, multicenter, observational, ambi-spective registry designed to evaluate the aortopathy progression in consecutive BAV patients undergoing TAVI. RESULTS: All patients with native bicuspid aortic valve who underwent TAVI for severe aortic stenosis between January 2018 and December 2019 with available preprocedural computed tomography angiography (CTA) assessment are considered. The primary endpoint of the study is to assess the progression of BAV-associated aortopathy at follow-up. Secondary endpoints include long-term clinical outcomes and aortopathy-related events. CONCLUSIONS: The PROSPERO registry will provide real-world evidence on the evolution of BAV-associated aortopathy after TAVI. Its results may help define follow-up strategies and improve patient selection and management in this increasingly relevant population. TRIAL REGISTRATION: ClinicalTrials.govNCT06248294.
BACKGROUND: Aortic stenosis (AS) impairs health-related quality of life but the prognostic impact of patient-reported health status prior to transcatheter aortic valve replacement (TAVR) is not fully established. OBJECTI...BACKGROUND: Aortic stenosis (AS) impairs health-related quality of life but the prognostic impact of patient-reported health status prior to transcatheter aortic valve replacement (TAVR) is not fully established. OBJECTIVES: To investigate the association of patient-reported health status at baseline with clinical outcomes and health status after transfemoral TAVR in patients with symptomatic severe AS. METHODS: In the investigator-initiated, multicenter SCOPE I randomized trial, patients underwent TAVR who provided baseline Kansas City Cardiomyopathy Questionnaire (KCCQ) assessment were included in this post hoc analysis. An integrated patient-centered outcome was defined as being alive with good health status (KCCQ overall summary score [KCCQ-OS] ≥ 75 without a decline of >10 points from baseline). RESULTS: Of 739 patients enrolled in SCOPE I, 692 were included in the present analysis. Median baseline KCCQ-OS was 54.9 (39.6-71.9) distributed as follows: KCCQ-OS < 25-74 (10.7%), 25 to 49-222 (32.1%), 50 to 74-271 (39.2%), and ≥ 75-125 (18.1%). At 3 years after TAVR, higher baseline KCCQ-OS was associated with a greater likelihood of being alive with good health status (KCCQ-OS 50-75 vs 0-25: adjusted odds ratio 2.25, 95% confidence interval [CI] 1.12-4.54; 75-100 vs 0-25: adjusted odds ratio 5.15, 95% CI 2.33-11.3). Restricted cubic spline modelling demonstrated an approximately linear relationship between baseline KCCQ-OS and all-cause mortality, and alive with good health status. CONCLUSIONS: In this post hoc analysis of SCOPE I, better baseline patient-reported health status was associated with a higher probability of being alive with good health status up to 3 years after TAVR. CLINICAL TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov/study/NCT03011346.
RATIONALE: Inclisiran is a small interfering ribonucleic acid targeting hepatic proprotein convertase subtilisin/kexin type 9 messenger RNA, that effectively reduces low-density lipoprotein cholesterol (LDL-C) levels. Th...RATIONALE: Inclisiran is a small interfering ribonucleic acid targeting hepatic proprotein convertase subtilisin/kexin type 9 messenger RNA, that effectively reduces low-density lipoprotein cholesterol (LDL-C) levels. The effect of inclisiran on cardiovascular (CV) outcomes has not been formally tested. METHODS: VICTORION-2 Prevent (NCT05030428) is an ongoing, Phase 3 randomized, double-blind, placebo-controlled, international trial assessing the efficacy and safety of inclisiran in preventing CV events in patients with established atherosclerotic cardiovascular disease (ASCVD) receiving high-intensity statin therapy. Patients with established ASCVD (history of myocardial infarction [MI], ischemic stroke, or symptomatic peripheral artery disease), and fasting plasma LDL-C ≥ 1.8 mmol/L (70 mg/dL) despite high-intensity statin therapy (≥ 20 mg rosuvastatin or ≥ 40 mg atorvastatin daily) will be enrolled. Patients will be treated with inclisiran sodium 300 mg or placebo, administered subcutaneously at Day 1, Day 90, and every 6 months thereafter. The primary outcome will include time to first occurrence of 3-point major adverse CV events (3P-MACE; composite of CV death, MI, or ischemic stroke). Secondary outcomes will include time to occurrence of CV death, time to first occurrence of 4P-MACE (composite of 3P-MACE and urgent revascularization), and major adverse limb event (all adjudicated outcomes), time to occurrence of all-cause death, and long-term safety of inclisiran. Safety will be monitored using a selective safety data collection strategy. CONCLUSION: VICTORION-2 Prevent will provide robust data on CV benefits and safety of inclisiran in patients with established ASCVD and not at guideline-recommended LDL-C goals despite high-intensity statin treatment. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT05030428.
BACKGROUND: Cardiac resynchronization therapy (CRT) using biventricular pacing (BiV-CRT) is an established treatment for patients with symptomatic heart failure, reduced left ventricular ejection fraction, and left bundl...BACKGROUND: Cardiac resynchronization therapy (CRT) using biventricular pacing (BiV-CRT) is an established treatment for patients with symptomatic heart failure, reduced left ventricular ejection fraction, and left bundle branch block (LBBB), leading to improvements in symptoms, ventricular function, exercise capacity and survival. Despite these benefits, up to one third of patients fail to respond optimally with no clinical improvement despite meeting current criteria for implantation. Conduction system pacing (CSP), delivered via His bundle pacing or left bundle branch area pacing, has emerged as an appealing alternative by directly engaging the native His-Purkinje system. However, randomized data directly comparing CSP-based CRT with conventional BiV-CRT remain limited. STUDY DESIGN: His-Alternative II is an investigator-initiated, multicenter, randomized non-inferiority trial designed to evaluate whether CRT delivered via CSP is non-inferior to conventional biventricular pacing with respect to left ventricular reverse remodeling. The study enrolls patients with symptomatic heart failure (New York Heart Association class II to III), left ventricular ejection fraction ≤35%, strict LBBB by electrocardiographic criteria, and optimal medical therapy. A total of 150 patients were randomized with a 1:2 randomization ratio to receive BiV-CRT or CSP-based CRT (His bundle pacing or left bundle branch pacing) and followed for 6 months. The primary endpoint is change in left ventricular end-systolic volume assessed by echocardiography; a surrogate endpoint consistently associated with long-term outcomes in CRT populations. Secondary endpoints include functional capacity, symptomatic status, quality of life, electrical resynchronization, and device-related complications. CONCLUSIONS: His-Alternative II is designed to determine whether CSP-based CRT can achieve left ventricular reverse remodeling comparable to that obtained with conventional BiV-CRT. The study will provide randomized evidence to inform the role of physiologic pacing strategies in contemporary CRT practice. GOV IDENTIFIER: NCT04409119.
BACKGROUND: Numerous risk scores exist to quantify the risk of ischemic stroke risk in patients with atrial fibrillation or flutter (AF/AFL). However, how these tools perform in cohorts or those already on oral anticoagu...BACKGROUND: Numerous risk scores exist to quantify the risk of ischemic stroke risk in patients with atrial fibrillation or flutter (AF/AFL). However, how these tools perform in cohorts or those already on oral anticoagulation (OAC) therapy is unclear. METHODS: Using 2 electronic health records datasets, individuals with AF/AFL were identified (Duke University Health System [DUHS]-2009-2018; 7 health systems participating in the Patient-Centered Clinical Research Network [PCORnet]-2015-2019). Individuals were stratified based on their OAC status at the time of entry into the cohort. Multivariable competing risk models for ischemic stroke and major bleeding were developed in the DUHS prevalent AF/AFL population and independently replicated in an incident AF/AFL within the PCORnet population. Discrimination of the final model for ischemic stroke was assessed against the CHADS-VASc model alone. RESULTS: During the study period, 214,749 unique patients with AF/AFL were identified (DUHS-43,896 with median CHA₂DS₂-VASc score 3; PCORnet-170,853 with median CHA₂DS₂-VASc 3), of which 41.1% were not on OAC, 32.1% were on a direct oral anticoagulant (DOAC), and 26.8% were on warfarin. The CHA₂DS₂-VASc model alone demonstrated modest discrimination for ischemic stroke across OAC strategies (C-index range 64%-69%). Incorporation of routinely available clinical variables substantially improved discrimination for ischemic stroke (C-index 74%-76% for no OAC, 74%-75% for DOAC, and 70%-72% for warfarin) and for major bleeding (C-index 75%-76% for no OAC, 75%-76% for DOAC, and 72%-73% for warfarin). Several factors not captured by CHA₂DS₂-VASc, including race and prior major bleeding, were independently associated with ischemic stroke risk. CONCLUSIONS: The CHA₂DS₂-VASc score provides modest discrimination for ischemic stroke and major bleeding across AF/AFL populations, including patients already treated with OAC. Incorporation of routinely available clinical factors substantially improves risk discrimination and highlights important sources of residual risk not captured by existing models.
It remains uncertain if direct oral anticoagulant monotherapy improves outcomes beyond bleeding risk compared with combination therapy with antiplatelets in chronic coronary syndrome patients with prior percutaneous coro...It remains uncertain if direct oral anticoagulant monotherapy improves outcomes beyond bleeding risk compared with combination therapy with antiplatelets in chronic coronary syndrome patients with prior percutaneous coronary intervention requiring anticoagulation. In this meta-analysis of randomized trials, direct oral anticoagulant monotherapy significantly reduced major adverse cardiac and cerebrovascular events and major bleeding without increasing ischemic events. The benefit in major adverse cardiac and cerebrovascular events was driven primarily by reductions in all-cause and cardiovascular mortality, supporting a bleeding-avoidance strategy in this high-risk population. TRIAL REGISTRATION: PROSPERO (CRD420251231341).
Regulatory science (RS) is a field dedicated to developing and applying scientific methods, tools, standards, and evidence-based frameworks to improve regulatory policies and decision-making related to medical and device...Regulatory science (RS) is a field dedicated to developing and applying scientific methods, tools, standards, and evidence-based frameworks to improve regulatory policies and decision-making related to medical and device products. The acceleration of cardiovascular innovations over the past two decades has underscored the need for efficient evidence generation and streamlined regulatory pathways for new drugs and devices. RS seeks to address these challenges by strengthening the evidence base that informs policy and guidance, enhancing transparency, expediting approval processes, and enabling more agile responses to emerging public health needs. By evaluating innovative trial designs and employing advanced statistical methods, RS can reduce resource demands of clinical trials while preserving scientific integrity. RS also facilitates the standardization of biomarker evaluations and surrogate endpoints, supporting advancements in precision medicine. In addition to clinical evaluation, RS can enhance post-marketing surveillance by utilizing real-world evidence and advanced analytics to promptly identify safety signals, ensuring patient safety and continuous product monitoring. RS also supports global regulatory harmonization efforts, reducing redundancies and accelerating access to therapies across regions. RS aims to guide the development of regulatory policies, refine communication strategies to optimize the use of medical products, and maintain efficient, transparent, and scientifically rigorous regulatory frameworks. Continued investment in RS is essential for improving patient outcomes in cardiovascular medicine by safeguarding safety while accelerating innovation and access to therapies.
BACKGROUND: While malnutrition has been shown to confer a poor long-term prognosis among patients with acute coronary syndromes, the influence of concomitant frailty has not been adequately considered. We aimed to evalua...BACKGROUND: While malnutrition has been shown to confer a poor long-term prognosis among patients with acute coronary syndromes, the influence of concomitant frailty has not been adequately considered. We aimed to evaluate the association between malnutrition severity and both in-hospital and 1-year outcomes among elderly STEMI patients receiving primary PCI. METHODS: This retrospective cohort study included STEMI patients ≥65 years who underwent primary PCI within the Vancouver Coastal Health Authority (2007-2020). Malnutrition was assessed using the Controlling Nutritional Status (CONUT) score based on serum albumin, total cholesterol, and lymphocyte count; scores 5-12 defined malnourishment. Frailty was quantified using a 31-item Frailty Index (FI) and modeled continuously in multivariable analyses. The primary outcome was in-hospital all-cause mortality. Secondary outcomes were a composite of adverse in-hospital events and 1-year all-cause mortality. RESULTS: Among 1,169 included patients, 315 (26.9%) were malnourished. After adjustment for age, sex, FI, and clinical covariates, increasing CONUT score (per 3-point increase) remained associated with in-hospital mortality (OR, 2.83; 95% CI, 2.01-3.97), composite in-hospital adverse outcomes (OR, 1.41; 95% CI, 1.12-1.77), and 1-year all-cause mortality (OR, 2.16; 95% CI, 1.41-3.31). Associations persisted after excluding frailty from the model. CONCLUSION: Approximately one in four elderly STEMI patients undergoing primary PCI were malnourished. Worsening malnutrition was associated with adverse in-hospital and 1-year outcomes, even after adjusting for frailty. Routine screening for malnutrition may help identify higher-risk patients and facilitate early risk stratification and targeted nutritional and rehabilitative interventions in STEMI care.
Moerdijk AS, van Genuchten WJ, Duijnhouwer AL
… +9 more, Snoeren MMM, Hirsch A, van den Berg LEM, Boersma E, Kauling RM, van den Bosch AE, Udink Ten Cate FEA, Helbing WA, Bartelds B
BACKGROUND: Exercise training is a promising, relatively low-cost strategy to optimize exercise capacity, primarily studied in patients with tetralogy of Fallot and Fontan physiology. However, rare and complex biventricu...BACKGROUND: Exercise training is a promising, relatively low-cost strategy to optimize exercise capacity, primarily studied in patients with tetralogy of Fallot and Fontan physiology. However, rare and complex biventricular disorders are understudied. High intensity interval training (HIIT) is a time-efficient alternative to the more commonly studied aerobic training. Despite group-level improvements in exercise capacity, individual variation suggests the existence of responders and non-responders to exercise training. We therefore designed a HIIT intervention trial for patients with complex outflow tract disorders aimed to test efficacy and identify predictors of response. METHODS: The Right HIIT study is a multicenter, randomized controlled trial aiming to enroll 38 patients aged 12 to 45 years with a right ventricle to pulmonary artery conduit. Participants will be randomized to a 12-week home-based HIIT program (intervention) or standard of care group. The primary endpoint is change in peak oxygen consumption from baseline to 12 weeks. Secondary endpoints include other cardiopulmonary exercise testing and imaging parameters, blood biomarkers, gut microbiome composition, quality of life and physical activity levels. After the randomized phase, the SoC group will receive the HIIT program, with repeated data collection after 12 weeks. Thus, pre-post HIIT data will be available in all patients, for the purpose of supportive analyses and identifying predictors of response. CONCLUSION: The Right HIIT study will analyze whether a HIIT program improves exercise capacity in patients with a right ventricle to pulmonary artery conduit and which factors are associated with the ability to improve exercise capacity. TRIAL REGISTRATION: ClinicalTrials.gov, NCT06771687, www. CLINICALTRIALS: gov/study/NCT06771687.
RATIONALE: Atrial fibrillation (AF) has roughly tripled in prevalence over the last 50 years. This disease disproportionately affects morbidity and mortality among older women. Increased physical activity has been associ...RATIONALE: Atrial fibrillation (AF) has roughly tripled in prevalence over the last 50 years. This disease disproportionately affects morbidity and mortality among older women. Increased physical activity has been associated with a lower incidence of new AF in some studies, but a higher incidence in others, especially among elite athletes. PRIMARY HYPOTHESIS: We designed a randomized trial within the Women's Health Initiative (WHI) Strong and Healthy (WHISH) trial to test the hypothesis that a pragmatic intervention consisting of multimodal messaging recommending physical activity levels consistent with national guidelines would decrease the incidence of AF among a cohort of older women. DESIGN: The present WHISH Silent Atrial Fibrillation Recording (WHISH STAR) trial randomized 29,758 postmenopausal women without baseline AF who were enrolled in Medicare Fee-for-Service to the aforementioned intervention or comparison group, with a planned 7-year follow-up to assess the primary outcome of incident clinical AF, namely those identified in Medicare claims. We also designed a sub-study of 1,257 women at high-risk for AF (with a CHARGE-AF score ≥5%) to undergo serial, 7-day electrocardiogram (ECG) patch monitoring to detect screened AF. We will use Cox proportional hazards models to compare the incidence of clinical AF in the participants assigned to physical activity intervention and the participants assigned to usual care groups. We will also compare the incidence of screened AF in the intervention and comparison groups detected on patch ECG monitors in the sub-study of women who underwent serial ECG patch monitoring. The WHISH STAR trial will rigorously evaluate the effect of a pragmatic physical activity intervention on the development of AF in a large, diverse, well-characterized cohort of older women. SITES: The WHISH trial is embedded within the nationwide WHI study, enrolling postmenopausal women from 40 United States clinical centers. ENROLLMENT DATES: Participants were enrolled in 2015 per the parent WHISH trial. CURRENT STATUS: WHISH STAR is in the analysis phase. TRIAL REGISTRATION: WHISH STAR has been registered on www. CLINICALTRIALS: gov (NCT05366803).
BACKGROUND: Conventional moderate-intensity continuous training (MICT) has certain shortcomings in enhancing peak oxygen consumption (VOpeak) and recovery of left ventricular function in post-percutaneous coronary interv...BACKGROUND: Conventional moderate-intensity continuous training (MICT) has certain shortcomings in enhancing peak oxygen consumption (VOpeak) and recovery of left ventricular function in post-percutaneous coronary intervention (PCI) acute myocardial infarction (AMI) patients, while high-intensity interval training (HIIT) raises safety concerns despite evidence of its effectiveness. OBJECTIVE: To assess the efficacy and safety of combined HIIT and MICT training compared to single training modalities in post-PCI AMI patients. METHODS: This single-center, three-arm parallel, assessor-blinded randomized controlled trial enrolled 204 clinically stable post-PCI AMI patients, who were randomized 1:1:1 to combined training (HIIT+MICT, n = 68), MICT alone (n = 68), or HIIT alone (n = 68) groups for 12-week supervised cardiac rehabilitation. The primary outcome was the change in VOpeak; secondary outcomes included left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), exercise capacity, and major adverse cardiovascular events (MACE). RESULTS: Combined training showed superior improvement in VOpeak (5.6 ± 2.3 mL/kg/min) compared with MICT alone (2.7 ± 1.9 mL/kg/min, P < .001) and HIIT alone (4.2 ± 1.8 mL/kg/min, P = .003), with 76.7% reaching clinically meaningful improvement (≥3 mL/kg/min). In the combined training group, LVEF increased 8.6 ± 3.2% and NT-proBNP decreased -706 pg/mL. Incidence of MACE remained low at 2.9%, without significant inter-group differences, P = .85. CONCLUSIONS: Combined HIIT and MICT training produces synergistic effects, superior to single modalities, in improving cardiopulmonary function and cardiac remodeling in post-PCI AMI patients, with comparable safety profile, providing evidence-based optimization strategy for cardiac rehabilitation. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR); Registration No. ChiCTR2000031251; https://www.chictr.org.cn/showproj.html?proj=31251.
BACKGROUND: Patients with atrial fibrillation (AF) and kidney failure are at particularly high risk of both thromboembolic and bleeding complications. The safety and efficacy of oral anticoagulation in this population re...BACKGROUND: Patients with atrial fibrillation (AF) and kidney failure are at particularly high risk of both thromboembolic and bleeding complications. The safety and efficacy of oral anticoagulation in this population remain uncertain, as pivotal direct oral anticoagulant (DOAC) trials excluded patients with kidney failure and warfarin has been associated with excess bleeding risk. Left atrial appendage (LAA) closure may provide an alternative strategy in stroke prevention, but has not been tested in randomized trials in dialysis-dependent patients. METHODS/DESIGN: The LAA-KIDNEY trial is a prospective, multicenter, randomized controlled clinical trial comparing percutaneous LAA closure with best medical care (including DOAC therapy whenever considered feasable) in patients with non-valvular AF and kidney failure at high risk of both, ischemic stroke and bleeding. A total of 272 patients will be randomized 1:1 across ∼35 centers in Germany, Belgium and the Czech Republic. The primary efficacy endpoint is net clinical benefit defined as time to a composite of first stroke (including ischemic or hemorrhagic strokes), systemic embolism, cardiovascular or unexplained death or major bleeding (BARC 3-5). Secondary endpoints include individual components of the composite outcome, myocardial infarction, cardiovascular hospitalization, cognitive function, quality of life, and device-related complications. Analysis will be performed in the intention-to-treat population. CONCLUSION: LAA-KIDNEY is the first randomized trial to evaluate LAA closure versus best medical care in AF patients with kidney failure. This trial will address a major evidence gap and is expected to inform clinical practice and guideline recommendations for stroke prevention in this high risk population. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT05204212.
RATIONALE: Two methods to select statin therapy for primary prevention are the pooled cohort equation (PCE), based on traditional risk factors, and coronary artery calcium (CAC), a patient-level assessment of coronary pl...RATIONALE: Two methods to select statin therapy for primary prevention are the pooled cohort equation (PCE), based on traditional risk factors, and coronary artery calcium (CAC), a patient-level assessment of coronary plaque burden. How well these methods compare in reducing atherosclerotic cardiovascular disease (ASCVD) outcomes is unknown. PRIMARY AIM: The CorCal Outcomes trial is designed to evaluate the effectiveness of CAC compared to the PCE as a guide to statin initiation in preventing ASCVD events. DESIGN: CorCal Outcomes is a randomized trial comparing CAC to PCE to guide statin initiation in nondiabetic primary prevention patients. The study has a noninferiority design and will utilize a modified per-protocol approach that includes all who completed baseline testing and received a statin recommendation. Here we describe the study design and patient population. ENROLLMENT: From October 30, 2019, to March 25, 2025, 75,539 patients were screened via medical record query and randomly invited to participate; 5,772 agreed to be enrolled and were randomized (2886 per arm). Of those, 5,329 completed the necessary testing to be included in the primary analysis (PCE = 2,642 [49.6%], CAC = 2,687 [50.4%]). CHARACTERISTICS: Average age is 64.3 ± 6.8 years, and 51.5% are female. Baseline demographics are well-matched between arms. The recommendations of the Data Safety Monitoring Board of December 9, 2024, and the Study Team's response are reported. CURRENT STATUS: Enrollment in CorCal Outcomes has resulted in well-balanced characteristics in the 2 arms used to recommend a statin. Based on study progress as of December 2024, the study is projected to end in second quarter of 2026. TRIAL REGISTRATION: This study is registered with Clinicaltrials.gov (NCT03439267).
Shah B, Lerner J, Martin J
… +8 more, Patrick Crane B, Andrade O, Li X, Xia Y, Yu C, Testa PA, Rao SV, Pragmatic Randomization Integrated into the Medial Record (PRIME) Investigators
BACKGROUND: Decisions involving the purchase of procedural equipment at the health system level require balancing efficacy, safety, physician preference, and cost. The application of efficient and low-cost pragmatic stud...BACKGROUND: Decisions involving the purchase of procedural equipment at the health system level require balancing efficacy, safety, physician preference, and cost. The application of efficient and low-cost pragmatic study designs has the potential to rapidly generate data to inform health system operations. METHODS: The aim of the pragmatic Radial Access Insertion Sheath Evaluation via the electronic medical record (RAISE-EMR) study is to determine physician preference between 2 commercially available radial artery introducer sheaths, one of which has a higher acquisition cost, to guide inventory selection in the hospital system's catheterization laboratories. Patients undergoing coronary angiography using 6-French radial artery access were prospectively identified and randomized through the health system's EMR. Among 1696 eligible unique patients, 554 patients (32.7%) were randomized over 37 days across 3 hospitals. Randomization took place through the EMR after the attending interventional cardiologist signed a mandated pre-procedure note. The study was deemed non-human subject research and approved by the New York University (NYU) Langone Health Quality Improvement Oversight Committee. The primary endpoint, a physician satisfaction score, will be ascertained by a mandated semi-quantitative survey within the electronic procedure note. All data, including co-variables and clinical outcomes, will be ascertained using structured data within the EMR. CONCLUSIONS: The Radial Access Insertion Sheath Evaluation via the EMR study is designed to determine physician preference of 2 commercially available radial artery introducer sheaths and potentially reduce supply costs using an entirely EMR-based randomized study design. Pragmatic study designs leveraging structured data within an EMR can be used to rapidly provide data to inform operational decision-making and have implications for the future of evidence generation. TRIAL REGISTRATION: ClinicalTrials.gov (identifier: NCT07218406).
BACKGROUND: In the EXSCEL trial, exenatide did not reduce major adverse cardiovascular events (MACE), but heterogeneity of benefit and the role of cardiac biomarkers remain uncertain. We evaluated the prognostic value of...BACKGROUND: In the EXSCEL trial, exenatide did not reduce major adverse cardiovascular events (MACE), but heterogeneity of benefit and the role of cardiac biomarkers remain uncertain. We evaluated the prognostic value of baseline and 1-year changes in N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (cTnI), and whether baseline biomarker concentrations modified exenatide effects. METHODS: EXSCEL randomized 14,752 adults with type 2 diabetes to exenatide 2 mg weekly (EQW) or placebo. In a biomarker cohort, 4,292 participants had serial NT-proBNP or cTnI at baseline and 1 year. Biomarkers were log transformed and Cox models related baseline concentrations and 1-year change to MACE, all-cause mortality (ACM), cardiovascular (CV) death, hospitalization for heart failure (hHF), adjusting for clinical covariates and the alternate biomarker. Treatment interaction was tested with biomarker by treatment terms. RESULTS: Over median 1,480 days follow-up, 529 MACE, 310 all cause deaths, 193 CV deaths, and 157 hHF events occurred. Baseline NT-proBNP was strongly prognostic (adjusted HR per 1 integer unit 1.63 for MACE, 1.85 for ACM, 2.17 for CV death, and 2.17 for hHF; all P < .001). Baseline cTnI was also prognostic with a nonlinear pattern, with risk rising mainly above the median. Per SD rise in NT-proBNP over 1 year predicted later MACE (HR 1.85) and CV death (HR 2.81; both P < .001). Baseline NT-proBNP didn't modify treatment effects. Baseline cTnI didn't modify EQW treatment effect on MACE but lower rates of CV deaths and hHF with EQW were observed at higher cTnI concentrations. CONCLUSIONS: NT-proBNP and cTnI were strong prognostic markers of adverse outcomes in patients with type 2 diabetes and their 1-year increases signaled higher subsequent risk. Baseline cTnI may mark heterogeneity of EQW response, but mortality interactions are hypothesis generating and require confirmation.