Incretin-based therapy has moved from glycaemic control into the centre of cardiometabolic medicine. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) consistently reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes (T2DM) and established atherosclerotic cardiovascular disease (ASCVD), while semaglutide 2.4 mg has extended the evidence base to people with overweight or obesity and established cardiovascular disease in the absence of diabetes. Dedicated trials have further expanded the clinical landscape to chronic kidney disease (CKD), obesity-related heart failure with preserved ejection fraction (HFpEF), and symptomatic peripheral artery disease (PAD). Concurrently, dual and triple incretin-based agonists, oral peptide and non-peptide formulations, and combination strategies with sodium-glucose cotransporter-2 (SGLT2) inhibitors and non-steroidal mineralocorticoid receptor antagonists are reshaping treatment algorithms. This critical review synthesizes cardiovascular outcome trials (CVOTs), mechanistic studies, meta-analyses, guideline recommendations, and regulatory developments available up to 30 April 2026. The central conclusion is that incretin-based cardiovascular protection is biologically plausible and clinically reproducible. Critically, this benefit is now independent of diabetes as the defining therapeutic context-a paradigm shift with broad implications for cardiovascular practice. Nevertheless, the magnitude of benefit varies considerably by molecule, dose, population, comparator, and endpoint hierarchy; mediation analyses do not precisely quantify direct cardioprotection; and cardiovascular outcome evidence for newer multi-agonists and oral non-peptide GLP-1 RAs remains incomplete. Interpretation therefore requires a balanced evidence framework: GLP-1 RAs with proven outcome benefit should be prioritized in patients with ASCVD (e.g., LEADER, SUSTAIN-6, HARMONY Outcomes), obesity with established CVD (SELECT), CKD (FLOW), or obesity-related HFpEF (STEP-HFpEF) when supported by trial data and regulatory indications, whereas next-generation agents should be evaluated according to completed CVOTs rather than weight-loss efficacy alone. Remaining research priorities include defining weight-independent mechanisms, optimizing combination therapy, identifying biomarker-defined responders, preserving lean mass during high-efficacy weight loss, and ensuring equitable global access.
Data on the prognostic value of incidental coronary artery calcium (CAC) from nongated chest computed tomography scans are limited. Using paired computed tomography scans from the MESA (Multi-Ethnic Study of Atherosclerosis) exam 5, we evaluated the relationship between nongated CAC, gated CAC, and future cardiovascular events. Between April 2010 and December 2011, a total of 2601 participants underwent same-day gated and nongated chest computed tomography scans. After excluding 106 with previous coronary heart disease or cardiovascular disease and 23 for missing covariates, 2472 participants formed the study population. Gated and nongated scans were interpreted at a core laboratory, blinded to acquisition methodology. Cox regression examined associations between CAC (gated and nongated) and incident coronary heart disease/cardiovascular disease events. Correlation was assessed with Pearson coefficients, model performance with receiver operating characteristic curves and C-statistic, and overall accuracy with Brier scores. Among the 2472 participants, 53% were female, 38% white, 13% Chinese, 26% Black, and 23% Hispanic/Latino. Compared with participants with zero CAC, those with moderate (101-299) and severe (≥300) nongated CAC had higher coronary heart disease risk (hazard ratio, 2.67 [95% CI, 1.14-6.27]; hazard ratio, 5.22 [95% CI, 2.37-11.5]) and cardiovascular disease risk (hazard ratio, 1.32 [95% CI, 1.32-4.04]; hazard ratio, 2.89 [95% CI, 1.68-4.96]). Gated and nongated log-standardized CAC highly correlated (r=0.961; P<0.001). The area under the receiver operating characteristic curves, C-statistic, and Brier scores were statistically similar for gated and nongated CAC. Nongated CAC predicts cardiovascular events with performance comparable to gated CAC. Given the large number of nongated scans performed annually, incorporating their quantification into clinical practice offers a scalable approach to personalized preventive care. Our findings are particularly relevant in light of the recent 2026 American College of Cardiology/American Heart Association dyslipidemia guidelines, which endorse the use of incidental CAC from nongated computed tomography scans for atherosclerotic cardiovascular disease risk stratification and guiding lipid-lowering therapy.
Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease, particularly when hypertension coexists. However, evidence regarding the role of cardiac rehabilitation (CR) in this high-risk population remains limited. In this randomized controlled trial, the effects of a structured CR program on estimated cardiovascular risk, ambulatory blood pressure, and cardiorespiratory fitness were evaluated in patients with RA and hypertension. In this single-center randomized controlled trial, 50 patients with RA and hypertension were randomly assigned (1:1) to a 6-week supervised CR program or usual care. The intervention included supervised aerobic, resistance, and flexibility training together with weekly educational sessions. Outcomes were assessed at baseline and at 6, 12, and 24 weeks by blinded evaluators. The primary outcome was estimated 10-year cardiovascular risk assessed using the Framingham Risk Score (FRS), with QRISK3 analyzed as a supportive risk measure. Secondary outcomes included 24-h ambulatory systolic blood pressure measured by ambulatory blood pressure monitoring (ABPM), cardiorespiratory fitness assessed by treadmill cardiopulmonary exercise testing (VO2max), and rheumatoid arthritis disease activity (DAS28-CRP). Longitudinal changes were analyzed using linear mixed-effects models according to the intention-to-treat principle. Linear mixed-effects modeling demonstrated a significant group × time interaction for FRS (p < 0.001). At Week 24, the between-group difference in FRS was -5.02 points (95% CI -8.60 to -1.44; p = 0.007). QRISK3 showed a similar directional reduction but did not reach statistical significance at Week 24 (-5.77 points; 95% CI -12.54 to 1.01; p = 0.094). Significant group × time interactions were also observed for 24-h ambulatory systolic blood pressure (p < 0.001) and VO2max (p < 0.001). At Week 24, the between-group difference was -9.70 mmHg for ambulatory systolic blood pressure and + 4.90 mL·kg-1·min-1 for VO2max. Disease activity remained within the remission range throughout follow-up. In selected patients with clinically stable rheumatoid arthritis and coexisting hypertension who were receiving stable pharmacologic therapy and were able to participate in supervised exercise, a structured cardiac rehabilitation program was associated with improvements in estimated cardiovascular risk profiles, ambulatory systolic blood pressure, and cardiorespiratory fitness without worsening disease activity. These findings support further evaluation of cardiac rehabilitation as an adjunctive strategy for cardiovascular risk management in a selected cardiometabolically high-risk rheumatoid arthritis population with hypertension. The trial was registered at ClinicalTrials.gov Identifier: NCT06295848.
Non-communicable diseases (NCDs), including cardiovascular diseases, diabetes, cancers and chronic respiratory diseases, account for a substantial proportion of global mortality and morbidity and represent a major challenge for the health system worldwide. Effective prevention and mitigation of NCDs requires coordinated strategies that combine health system interventions with population-level policies targeting key risk factors such as tobacco use, harmful alcohol consumption, unhealthy diets and physical inactivity. Evidence on actionable strategies implemented across diverse health systems and policy contexts remains fragmented. This scoping review aims to map the range, nature and implementation contexts of actionable health system and policy strategies for the prevention and mitigation of NCDs. The review will follow the methodology outlined by the Joanna Briggs Institute for scoping reviews and will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A comprehensive search will be conducted across MEDLINE (via PubMed), Scopus, Web of Science, Embase, CINAHL, PsycINFO and Global Health. Grey literature sources such as government reports, national NCD strategies and documents from international organisations will also be searched to capture policy and implementation evidence. Studies involving populations at risk of or living with NCDs and describing health system or policy interventions aimed at prevention or mitigation will be eligible. Study selection will be conducted in two stages-title and abstract screening followed by full-text review-by two independent reviewers using predefined criteria based on the Population-Concept-Context framework. Data will be extracted using a standardised charting form capturing bibliographic information, study characteristics, intervention types, implementation contexts and outcomes, then summarised by geographical region, study design and intervention type. A thematic synthesis will categorise interventions into major domains such as health system-based strategies and population-level policy interventions. Findings will be presented through narrative summaries, tables and evidence maps. This scoping review involves only secondary analysis of published and publicly available literature, and does not involve primary data collection, so no ethical approval is required. The findings will be disseminated through peer-reviewed journal publications and conference presentations.
While interventional cardiology has a significant environmental footprint, the level of engagement of professionals in mitigating their ecological impact remains unexplored. The GREEN-CCF (Global Review of Environmental Expectations in Cardiac Catheterization in France) study aimed to assess current practices, perceptions, and expectations of interventional cardiology professionals in France about their environmental impact. An online survey was developed and distributed to health care professionals involved in cardiology across France. The target population included senior cardiologists, cardiologists in training, nurses, medical imaging technicians, and research staff. The questionnaire explored participants' knowledge and motivation on environmental issues, current waste management practices in catheterization laboratories, and perceived barriers and potential solutions to reducing their professional environmental footprint. Among 859 participants who submitted fully completed responses, 367 (43%) were involved in interventional cardiology. Despite a high level of motivation on the environmental issues, the participants reported low levels of knowledge and perceived motivation of their centers. More than 70% of participants reported discarding materials used during procedures, including packaging, plastics, and specific materials. The most frequently cited barrier to reduce the environmental impact of interventional cardiology practices was the difficulty in changing professional behaviors (47%). The most frequently proposed actions to reduce the environmental impact of interventional cardiology were improving the durability of materials (42%), implementing standardized recommendations (33%), reducing product packaging (48%), and adopting incentives or regulatory requirements (34%). These findings reinforce the need of addressing environmental sustainability in interventional cardiology. While professionals are motivated and aware of the challenges, structural and institutional changes are needed to support future interventions.
Cardiology services are among the most frequently used and costly services and procedures in US health care. Understanding price variation is essential for employers, patients, and policymakers to make informed decisions, contain costs, and promote value-based care. To assess the extent of variation in commercial insurance payment rates for common cardiology services across major US insurers and states using newly available Transparency in Coverage (TIC) data. This cross-sectional study used April 2025 TIC data from a third-party vendor reflecting 2023 contract year claims. The dataset included approximately 6.7 million professional and 104 563 facility price points for 32 common cardiology services across 4 major commercial insurers (Blue Cross Blue Shield, UnitedHealthcare, Aetna, and Cigna Healthcare), representing 78% of the commercial insurance market. The sample covered 51 568 physicians and 4128 facilities nationwide. Negotiated allowed amounts paid by 4 major insurers for cardiology services, analyzed by Current Procedural Terminology code and grouped into categories such as diagnostic imaging, electrophysiology, and stress testing. Variation in allowed payment amounts for each cardiology service across insurers and states. Measures included median prices and IQRs, coefficients of variation, and volume-weighted price indices. Facility negotiated price variation exceeded professional fee variation, with a median interquartile ratio of 2.56 across services. For example, median facility fees for implantable cardioverter-defibrillator (ICD) insertion ranged from $6674 (IQR, $3069-$11 402) to $36 269 (IQR, $18 673-$66 880) across insurers. Geographic variation was also substantial, with a median facility price for coronary angiography of $7683 (IQR, $4561-$10 101) across states. Blue Cross Blue Shield had the highest mean facility prices while Aetna had the lowest across most service categories. In this cross-sectional study of commercial insurance payments for cardiology services, there was substantial variation across both insurers and states, particularly in facility fees. These findings reveal the influence of payer contracting strategies and market dynamics and underscore the need for greater transparency and regulatory oversight to promote efficient health care spending.
Prospective clinical research studies are challenged by low enrollment rates and underrepresentation of individuals from racial and ethnic minority groups. To determine the effect of electronic message content on study enrollment among racial and ethnic groups. Four sequential randomized clinical trials (RCTs) were conducted between October 30, 2023, and November 13, 2024, in which University of Pennsylvania Health System patients (aged ≥18 years) were contacted electronically via email, text message, or both. The most effective arm from each RCT served as the control in the subsequent observational study. This analysis of all 4 RCTs was performed on the intention-to-treat principle from December 2024 through September 2025. Messages varied by method, source, framing, and incentive structure. The primary outcome was enrollment fraction (number enrolled divided by total contacted) among Black and Hispanic participants. Overall enrollment fraction was a secondary outcome. Overall, 26 215 patients were contacted and 26 029 were offered enrollment in the Penn Medicine BioBank; 63.2% were Black and 7.2% were Hispanic. Their mean (SD) age was 60.5 (17.9) years, and 60.1% were female. In the first recruitment RCT (RCT 1) (n = 8038), the enrollment fraction among 4581 Black and Hispanic patients was 0% with email, 0.5% with text, and 0.2% with email plus text (P = .06 for text vs email; P = .20 for email plus text vs email). Due to technical issues, more than 80% of participants who attempted to consent in RCT 1 failed; consent attempts were higher with text (4.8%) and email plus text (4.4%) than email alone (0.6%) (P < .001 for text vs email and email plus text vs email). In RCT 2 (n = 4271), the enrollment fraction among 1902 Black and Hispanic patients was 1.0% with research team outreach and 1.8% with clinical team outreach (P = .12). In RCT 3 (n = 3217 Black and Hispanic patients), the enrollment fraction was 3.2% with a control message, 3.6% with an appeal to altruism, and 4.1% with an appeal to social proof (P > .05 for all comparisons). In RCT 4 (n = 10 689), the enrollment fraction among 8629 Black and Hispanic patients was 2.5% with no incentive, 6.8% with $25, 5.5% with $15 plus a 5% chance at $200, 5.8% with a 5% chance at $500, and 6.5% with a 1% chance at $2500 (P < .001 for each incentive vs no incentive; P > .05 for each incentive compared with another). In this series of RCTs, the enrollment fraction among Black and Hispanic patients was improved with outreach by text message and with an incentive. ClinicalTrials.gov Identifier: NCT05827718.
Background and Objectives: Cardiovascular diseases (CVDs) are the leading cause of global morbidity and mortality, and significantly influence perioperative risk in non-cardiac surgery. This study aimed to evaluate the prevalence of cardiovascular comorbidities and their immediate impact on perioperative management in a tertiary surgical center. Materials and Methods: A retrospective cohort study was conducted including all adult patients undergoing elective or emergency non-cardiac surgery between January 2022 and December 2024. Demographic data, primary diagnoses, cardiovascular comorbidities, chronic medication, and perioperative management modifications were analyzed. Descriptive statistical analysis was performed using SPSS v16. Results: A total of 5716 patients were included. Cardiovascular comorbidities were identified in 2157 patients (37.37%). Hypertension (HTN) was the most prevalent condition (33.37%). Surgical delay due to anticoagulation occurred in 4.16% of cases, postponement due to cardiovascular instability in 1.27%, and surgery was contraindicated in 0.50%. Conclusions: Cardiovascular comorbidities are highly prevalent among patients undergoing non-cardiac surgery and frequently require modification of perioperative management strategies. Further studies incorporating postoperative outcomes are needed to better define their impact on surgical prognosis. Structured cardiovascular risk assessment aligned with ESC (European Society of Cardiology) guidelines appears clinically justified, although future outcome-based studies are required.
Background and Objectives: A relationship between cognitive decline (CD) and chronic coronary syndrome (CCS), common among the elderly population, has not yet been clearly established. Our study aims to evaluate the link between severe cognitive impairment and cognitive impairment, as measured by various neuropsychological tests in patients with or without CCS. In addition, we sought to identify cardiovascular risk factors (CVRFs) that influence the severity of CD and severe cognitive impairment. Materials and Methods: This observational study was conducted on 264 people with CVRFs. Of the 264, 132 were classified as patients with CCS and 132 as control subjects without CCS. Neuropsychological assessment tools included the Instrumental Activities of Daily Living (IADL) and Activities of Daily Living (ADL) scales, the Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), and the Geriatric Depression Scale (GDS-15). Clinical characteristics, echocardiographic measures, and vascular parameters of all subjects were also evaluated. Results: Patients with CCS had significantly lower cognitive performance (MMSE, p = 0.010; MoCA, p = 0.021), reduced functional status (IADL, p = 0.030; ADL, p = 0.012), and higher depression scores (p = 0.004) compared with controls. They also had worse cardiovascular profiles, including lower left ventricular ejection fraction (LVEF) (p = 0.001), higher NT-proBNP levels (p = 0.005), and increased carotid intima-media thickness (IMT) (p < 0.05). IMT and blood pressure values were negatively correlated with cognitive and functional scores and positively correlated with depression severity (p < 0.001). Multivariate analysis identified systolic and diastolic blood pressure, age, body mass index, heart rate, reduced daily activity, and depression as independent predictors of cognitive decline in patients with CCS. In the GDS-15 score, each unit increase was associated with a 32.1% higher risk of cognitive decline and a 37.1% higher risk of MMSE-defined severe cognitive impairment, while improved ADL scores significantly reduced this risk. Conclusions: CCS is associated with an increased risk of severe cognitive impairment and also with cognitive decline, influenced by hypertension, subclinical atherosclerosis, depression, and reduced functional status. These findings emphasize the importance of early identification and multidisciplinary management of cognitive impairment in patients with CCS to prevent progression to severe cognitive impairment.
Hypertensive disorders of pregnancy (HDP) affect 5-10% of pregnancies globally and are a leading cause of maternal and fetal morbidity and mortality. Beyond their acute obstetrics impact, HDP unmask a lifelong cardiovascular (CV) vulnerability in affected women and confer intergenerational risk to their offspring. PURPOSE OF REVIEW: In this review, we discuss the latest evidence regarding the CV risk profiles following HDP in the mothers and their offspring. RECENT FINDINGS: In mothers, HDP is associated with a 7.29-fold increased risk of new chronic hypertension (HTN) within 24 months postpartum and long-term risks of heart failure, coronary heart disease and stroke. Offspring exposed carry a 1.5-fold increased risk for adult HTN and increased risks for ischemic heart disease and stroke. We review evidence on potential pathophysiologic mechanisms including shared genetic, epigenetic programming and persistent immune dysregulation that contribute to the CV risk. We make recommendations on surveillance strategies in mothers and their offspring beginning in the immediate postpartum period and for lifelong follow-up. Management strategies of the CV risk factors, using latest guidelines are discussed. We suggest future directions for research and intervention. Integrated maternal-offspring CV care, women-specific risk prediction tools and equity focused research are needed to reduce the intergenerational burden of HDP.
Hypertension prevalence rises dramatically with advancing age, is not well controlled with current therapy, and contributes substantially to cardiovascular, renal, and neurological disorders that are common in the elderly. The renin-angiotensin-aldosterone system is a hormonal pathway with multiorgan involvement critical to controlling blood pressure. The production of the steroid hormone aldosterone and the activation state of its MR (mineralocorticoid receptor) are important clinical targets for hypertension treatment and cardiorenal disease prevention. This review summarizes studies demonstrating that aging is associated with (1) dysregulation of adrenal aldosterone production by autonomous aldosterone-producing adrenal cells and, when comorbid with obesity, by factors released from adipose tissue that promote adrenal aldosterone production; (2) increased expression of the MR due to oxidative stress-activated and inflammation-activated transcription factors; and (3) aldosterone-independent MR activation by oxidative stress-activated Rac1 (Ras-related C3 botulinum toxin substrate 1), angiotensin II signaling, and declining expression of the cortisol-inactivating enzyme 11β-HSD2 (11-beta-hydroxysteroid dehydrogenase type 2). Together, these data support the concept that elderly individuals are at high risk for mineralocorticoid-driven hypertension and associated cardiovascular, renal, and neurological disease. The review further describes the different classes of agents that inhibit this pathway, including traditional steroidal MR antagonists, newer nonsteroidal MR antagonists, and aldosterone synthase inhibitors, comparing their modes of action. The steroidal MR antagonists and nonsteroidal MR antagonists have different degrees of MR selectivity and potency, yet they all block MR activation by aldosterone, cortisol, and ligand-independent mechanisms. The aldosterone synthase inhibitors block aldosterone production in the adrenal gland and attenuate aldosterone-mediated MR effects. All 3 drug classes raise potassium proportional to the degree of renal MR inhibition. Trials are summarized showing efficacy of the new agents in reducing MR activation, aldosterone production, blood pressure, and adverse cardiorenal outcomes. Head-to-head studies in older individuals are needed to determine the relative efficacy of aldosterone synthase versus MR inhibition for blood pressure control to improve outcomes in the elderly and very old.
The American Heart Association introduced cardiovascular-kidney-metabolic (CKM) health as an integrated framework for metabolic, kidney, and cardiovascular risk. However, full AHA CKM staging requires variables that are often unavailable in retrospective outpatient datasets, and outcome data from Southeast Asia remain limited. To evaluate whether pragmatic CKM burden categories derived from routinely available baseline diagnoses identify Vietnamese outpatients at higher risk of 5-year all-cause mortality. We performed a retrospective cohort analysis of 480 adult outpatients recruited from 01 January 2016-31 December 2016 in Ho Chi Minh City, Vietnam. The de-identified dataset for this secondary analysis was accessed on 31 March 2024. Participants were classified into four mutually exclusive pragmatic CKM burden categories: Category A, no documented metabolic-risk diagnosis, chronic kidney disease (CKD), or coronary artery disease (CAD); Category B, documented metabolic-risk diagnosis only; Category C, CKD or CAD, but not both; and Category D, concomitant CKD and CAD. These categories are AHA-informed but are not official AHA CKM stages. The primary endpoint was 5-year all-cause mortality, with administrative censoring at 5 years. Logistic regression was the primary inferential model; Kaplan-Meier, log-rank, and Cox models were used as complementary time-to-event analyses. To support privacy-preserving data sharing, adjusted models used prespecified age groups (<40, 40-60, and >60 years) and sex rather than exact individual ages. Most participants were aged 40-60 years (331/480, 69.0%) and 204 (42.5%) participants were men. The category distribution was as follows: Category A, 24 (5.0%), Category B, 252 (52.5%), Category C, 180 (37.5%), Category D, 24 (5.0%). Over 2243.1 person-years of follow-up within the 5-year analysis horizon, 64 deaths occurred (13.3%). Five-year mortality was 0/24 (0.0%) in Category A, 33/252 (13.1%) in Category B, 24/180 (13.3%) in Category C, 7/24 (29.2%) in Category D. Kaplan-Meier curves differed across the four categories (log-rank p = 0.036). Compared with Categories A + B, Category D had higher unadjusted odds of 5-year mortality (OR 3.03, 95% CI 1.17-7.86; p = 0.022) and remained elevated after age-group and sex adjustment (OR 2.87, 95% CI 1.04-7.94; p = 0.042). Category C was not associated with higher adjusted 5-year mortality. In this Vietnamese outpatient cohort, pragmatic CKM burden categories identified a subgroup with combined CKD and CAD that had the highest absolute 5-year mortality. The age-group- and sex-adjusted estimate remained elevated for this small subgroup, although confidence intervals were wide. These categories should not be interpreted as official AHA CKM stages, and prospective validation with complete CKM phenotyping is needed.
Although the presence or absence of cardiovascular disease (CVD) recurrence is related to lifestyle habits, including diet, evidence for the maintenance of dietary improvement among participants with incident CVD after acute treatment is scarce. To determine changes in diet and other lifestyle factors in participants with incident CVD in the Japan Public Health Center-based Prospective Study (JPHC study) over a 5-year period before and after diagnosis by comparing changes with those in participants without a diagnosis of CVD. Participants were 68733 subjects aged 45-76 years at the baseline survey. Intakes of seven nutrients and 16 food groups were estimated using Food Frequency Questionnaires at the baseline survey and 5-year follow-up survey, and the amount of change was determined. Those diagnosed with CVD during the 5-year follow-up period were defined as participants with incident CVD (800 cases) and those not diagnosed were considered the non-CVD controls. Differences in the change between the two groups over the 5-year period were examined using the Mann-Whitney U test and multivariate linear regression analysis. Changes in smoking status, body mass index (BMI), and physical activity were compared by logistic regression analysis. CVD participants appeared to restrict sodium intake after diagnosis, and even after energy adjustment were more likely to avoid eating sodium, miso soup and pickles. In addition, they were less likely to eat beef and pork than controls. Significantly more CVD participants than controls stopped smoking and had decreased BMI. Participants with incident CVD showed modification in selective lifestyle factors, characterised by reduced sodium intake and smoking cessation.
Severe tricuspid regurgitation (TR) is associated with increased mortality and hospitalizations for heart failure (HF). Aetiologies of TR include: secondary (atrial or ventricular), primary and cardiac implantable electronic device (CIED)-related. The aim of the study was to assess the prevalence of different TR aetiologies, as well as characteristics and treatment of patients with severe TR in a real-life setting. This was a prospective, observational study of patients with severe TR, conducted in 18 cardiology centres. Consecutive adult patients with severe TR were included, regardless of the presence of TR symptoms and the cause of hospital admission. A total of 1295 patients with severe TR were enrolled (median age 76 years, 53% women). The most common reason for admission was HF decompensation (40%). Single TR aetiology was identified in 79% patients. The most frequent overlap between aetiologies included secondary ventricular and atrial TR, and was found in 11% of patients. The most common TR aetiology was secondary atrial (37%), followed by secondary ventricular (25%). Primary and CIED-related TR accounted for 10% and 15%, respectively. In 2.4% TR aetiology was not determined. Patients with secondary atrial and CIED-related TR were the oldest (79 and 78 years, respectively), and those with primary TR the youngest (68 years). Patients with CIED-related and secondary ventricular TR were more often hospitalized for HF decompensation, had more advanced HF symptoms, worse left- and right-ventricular function, worse kidney and liver function, and higher in-hospital mortality. Only 40% of patients underwent evaluation by the Heart Team and 21% were qualified for TR interventions. In real life, unequivocal identification of TR aetiology remains challenging. Secondary atrial TR is the most common aetiology. There are significant differences in characteristics and outcomes depending on TR aetiology. Too few patients with severe TR undergo evaluation by the Heart Team.
The decision to transfuse a patient with myocardial infarction (MI) and anemia at a higher vs lower hemoglobin threshold must consider the potential benefit of reduced risk of 30-day death or MI and the potential risk of heart failure. To estimate bayesian posterior risk differences and posterior probabilities that a liberal vs restrictive transfusion strategy is associated with reduced risk of 30-day death or MI and whether the probabilities exceed predefined thresholds. The Myocardial Ischemia and Transfusion (MINT) trial recruited adults from April 26, 2017, to April 14, 2023, who were hospitalized with MI and anemia at 144 sites in 6 countries. Statistical analysis was performed from July 31, 2024, to February 18, 2026. The MINT trial randomized participants to a restrictive (transfuse if hemoglobin is <7 to 8 g/dL) or liberal (maintain hemoglobin at >10 g/dL) transfusion strategy. Bayesian posterior risk differences were estimated for 30-day death or MI and for heart failure using 3 prior beliefs regarding the treatment strategies: noninformative, liberal strategy superiority, or restrictive strategy superiority. The mean (SD) age of the 3504 participants was 72.1 (11.6) years and 1911 (54.5%) were men. Compared with the restrictive strategy, the risk of 30-day death or MI with the liberal strategy was 1.4% (95% credible interval, -0.8% to 3.5%) to 2.4% (95% credible interval, 0.3%-4.6%) lower, depending on prior beliefs. The probability that the liberal strategy was associated with a lower risk of 30-day death or MI ranged from 89.1% to 98.8%, and the probability that a liberal strategy was associated with at least 1 less death or MI per 100 treated was between 62.7% and 90.4%. Conversely, the risk of heart failure with the liberal strategy was 0.2% (95% credible interval, -1.6% to 1.2%) to 0.6% (95% credible interval, -2.0% to 0.8%) higher compared with the restrictive strategy, depending on prior beliefs. The probability that the liberal strategy was associated with a higher risk of heart failure ranged from 60.6% to 80.0%, and the probability that a liberal strategy was associated with at least 1 more heart failure event per 100 treated was between 13.3% and 29.3%. This post hoc analysis of a randomized clinical trial of patients with MI and anemia suggests that a liberal transfusion strategy was associated with a lower risk of 30-day death or MI, outweighing the increased risk of heart failure. Consistent with guideline recommendations and according to patients' values and clinician risk assessment, a liberal transfusion strategy may be reasonable. ClinicalTrials.gov Identifier: NCT02981407.
The optimal duration of dual antithrombotic therapy after percutaneous coronary intervention (PCI) in patients with atrial fibrillation remains uncertain. We aimed to compare the efficacy and safety of 1-month versus 12-month dual antithrombotic therapy in this population. OPTIMA-AF was an active-control, randomised, hybrid non-inferiority and superiority trial in which patients with atrial fibrillation undergoing PCI with intravascular imaging guidance were randomly assigned (1:1) to receive 1-month dual antithrombotic therapy (direct oral anticoagulant [DOAC] plus P2Y12 inhibitor) followed by DOAC monotherapy or 12-month dual therapy followed by DOAC monotherapy, across 75 sites in Japan. Eligible patients were aged 20 years or older with non-valvular atrial fibrillation, a CHADS2 score of 1 or higher, undergoing PCI for native coronary lesions for chronic coronary syndrome or unstable angina, with planned post-PCI treatment with a DOAC. Randomisation used web-based central allocation stratified by trial centre. Investigators and patients were unmasked; clinical events were adjudicated by an independent committee masked to treatment. The primary efficacy endpoint was a composite of all-cause death or thromboembolic events at 12 months; the primary safety endpoint was major or clinically relevant non-major bleeding at 12 months. The trial used a fixed-sequence testing strategy of non-inferiority for efficacy, superiority for safety, and superiority for efficacy. Analyses used the full analysis set including all patients who underwent PCI, were randomly assigned to treatment, received at least one dose of study drugs, and met prespecified analysis-set criteria. This trial is registered with the Japan Registry of Clinical Trials (jRCTs051190053), and is complete. From Oct 7, 2019, to Sept 3, 2024, 1101 patients were assessed for eligibility; 1088 were randomly assigned to treatment and 1079 were included in the full analysis set (1-month dual therapy n=542; 12-month dual therapy n=537). Median age was 76 years (IQR 70-81). 225 (21%) of 1079 patients were female and 854 (79%) were male. Median CHADS2 score was 2 (IQR 2-3). Median follow-up was 540 days (IQR 517-559). The primary efficacy endpoint occurred in 29 patients in the 1-month dual therapy group and 23 patients in the 12-month dual therapy group (Kaplan-Meier estimate 5·4% vs 4·3%; absolute difference 1·1 percentage points [95% CI -1·5 to 3·6]; hazard ratio [HR] 1·25 [95% CI 0·73-2·17]). The primary safety endpoint occurred in 24 patients versus 47 patients (Kaplan-Meier estimate 4·5% vs 8·8%; absolute difference -4·4 percentage points [95% CI -7·3 to -1·4]; HR 0·50 [95% CI 0·30-0·81]; p=0·0041 for superiority). Among patients with atrial fibrillation and predominantly chronic coronary syndrome undergoing PCI with intravascular imaging guidance, 1-month dual antithrombotic therapy followed by DOAC monotherapy was non-inferior to 12-month therapy for death or thromboembolic events and reduced major or clinically relevant non-major bleeding at 12 months, suggesting an overall favourable net clinical profile. Efficacy findings should be interpreted with appropriate caution in light of the lower-than-anticipated event rates and fixed absolute non-inferiority margin. Abbott Medical Japan. For the Japanese translation of the abstract see Supplementary Materials section.
Background: Physiotherapists played central roles in high-risk 'red-zone' care during COVID-19 and reported substantial distress, yet mechanisms linking exposure to burnout remain unclear.Objective: To examine whether the association between direct patient contact and burnout operates through a stress-related behavioural mediator (feeling like quitting/taking a break) and whether organisational resources moderate this pathway.Methods: We conducted a secondary analysis of a nationwide, multicentre, web-based survey of Japanese physiotherapists engaged in COVID-19 care (March 2021). Burnout was defined using the Japanese MBI-GS case algorithm. Counterfactual mediation analysis with bias-corrected and accelerated (BCa) bootstraps (5,000 resamples) was used to estimate the average causal mediation effect (ACME), average direct effect (ADE), and total effect on the risk-difference scale. Models were adjusted for age, sex, years in practice, and cohabitation.Results: Burnout prevalence was 19.4%. A small indirect effect was observed (ACME = 0.00932; 95% CI 0.00188-0.0200), whereas the direct and total effects were not statistically significant. Appreciation/respect was associated with attenuation of the indirect effect (ACME = 0.00007), whereas endorsement of enhanced reimbursement for two-therapist care of critically ill patients was associated with a larger indirect effect (ACME = 0.00637; 95% CI 0.00122-0.0100). Because the primary mediation analysis used a binary mediator and binary outcome with logistic link functions, a formal ρ-based sensitivity analysis for unmeasured mediator-outcome confounding was not available under this specification.Conclusions: Among Japanese physiotherapists, the association between direct COVID-19 patient contact and burnout was consistent with an indirect pathway operating through a stress-related behavioural mediator. Recognition appeared to buffer this pathway, whereas reimbursement-linked resource strain appeared to amplify it. These findings suggest potentially relevant organisational targets for future intervention, but should be interpreted cautiously given the cross-sectional design and the causal assumptions required for mediation analysis. This nationwide survey of Japanese physiotherapists showed that the link between direct COVID-19 patient contact and burnout operated primarily through a behavioural mediator – feeling like quitting or taking a break.Recognition and respect buffered this indirect pathway, while reimbursement-related resource strain amplified it, underscoring the dual role of social and organisational contexts.Findings highlight modifiable, trauma-informed targets – staffing, remuneration, and authentic recognition – for protecting physiotherapists’ mental health during future crises. Introducción: Los fisioterapeutas desempeñaron funciones centrales en la atención de alto riesgo en las denominadas ‘zonas rojas’ durante la pandemia de COVID-19 y reportaron un malestar psicológico considerable. Sin embargo, los mecanismos que vinculan la exposición con el síndrome de burnout aún no están claros. Objetivo: Evaluar si la asociación entre el contacto directo con pacientes y el síndrome de burnout se transmite a través de un mediador conductual relacionado con el estrés (sentir deseos de renunciar o tomarse un descanso) y si los recursos organizacionales moderan esta vía. Métodos: Se realizó un análisis secundario de una encuesta nacional, multicéntrica y basada en la web dirigida a fisioterapeutas japoneses involucrados en la atención de pacientes con COVID-19 (marzo de 2021). El burnout se definió según los criterios de caso del Maslach Burnout Inventory–General Survey (MBI-GS). Mediante análisis de mediación contrafactual con remuestreo bootstrap corregido por sesgo y acelerado (BCa; 5.000 re-muestras), se estimaron el efecto promedio de mediación causal (ACME), el efecto directo promedio (ADE) y el efecto total en la escala de diferencia de riesgos. Los modelos paramétricos para el mediador y el desenlace se especificaron en la escala de probabilidad; los ajustes principales incluyeron edad, sexo, años de ejercicio profesional y convivencia con otras personas, además de análisis de sensibilidad para la confusión entre mediador y desenlace. Resultados: La prevalencia de burnout fue del 19,4%. Se observó un efecto indirecto pequeño pero consistente (ACME = 0.00932; IC 95%: 0.00188–0.020; p = 0.01), mientras que los efectos directo y total no fueron estadísticamente significativos. La percepción de aprecio y respeto eliminó el efecto indirecto (ACME = 0.00007; p = 0.78), mientras que la promoción de una mayor remuneración para la atención de pacientes críticamente enfermos por dos fisioterapeutas lo amplificó (ACME = 0.00637; IC 95%: 0.00122–0.010; p = 0.006). Las estimaciones fueron similares tanto para los efectos en los expuestos como en los no expuestos. Los análisis de sensibilidad indicaron que sería necesaria una confusión no medida de magnitud moderada entre el mediador y el desenlace para explicar completamente el ACME, mientras que las métricas de proporción mediada resultaron inestables debido a la cercanía del efecto total a la nulidad. Conclusiones: Entre los fisioterapeutas japoneses, la relación entre el contacto directo con pacientes con COVID-19 y el síndrome de burnout se transmitió principalmente a través de un mediador conductual modificable relacionado con el estrés. El reconocimiento actuó como factor amortiguador de esta vía, mientras que las tensiones vinculadas a los recursos y la remuneración la intensificaron, destacando objetivos organizacionales con enfoque informado en trauma, tales como una dotación adecuada de personal, una remuneración justa y un reconocimiento genuino.
To evaluate the efficacy and safety of antithrombotic treatment for migraine prevention in participants with patent foramen ovale (PFO). Investigator initiated, multicentre, prospective, randomised, active controlled, open label clinical trial with blinded outcome assessment and hierarchical hypothesis testing. Secondary and tertiary care hospitals across 39 centres in China. 1000 adults aged 18-64 years with a diagnosis of migraine for more than one year, experiencing at least four migraine days per month, and with PFO confirmed by echocardiography. All participants completed a 12 week screening period before randomisation during which eligibility was confirmed and baseline headache data were prospectively recorded. Participants with previous stroke, transient ischaemic attack, intracranial haemorrhage, non-PFO right-to-left shunt, or contraindications to study drugs were excluded. Of the randomised participants, 984 (75.1% female) were included in the full analysis set. After the screening phase, participants were randomised in a 1:1:1:1 ratio to receive aspirin (300 mg once daily), clopidogrel (75 mg once daily), rivaroxaban (20 mg once daily), or metoprolol (25 mg twice daily) for 12 weeks. No additional preventive migraine treatments were permitted during the intervention period. The primary outcome was the proportion of participants achieving a ≥50% reduction in monthly migraine days or attacks from baseline to weeks 9-12. Safety outcomes included bleeding and other adverse events. For the primary endpoint, aspirin, clopidogrel, and rivaroxaban were all non-inferior to metoprolol. Responder rates were 61.7% (148/240) with aspirin, 66.8% (157/235) with clopidogrel, 78.4% (185/236) with rivaroxaban, and 61.8% (144/233) with metoprolol. Rivaroxaban further showed a statistically higher responder rate than metoprolol, with an absolute difference of 16.2% (98.33% confidence interval 6.0 to 26.4; P<0.001). Among secondary endpoints, rivaroxaban was associated with greater reductions in migraine days and attacks, higher rates of complete migraine cessation, and greater improvements in migraine specific quality-of-life scores than metoprolol. No major bleeding events occurred. The antithrombotic agents evaluated in this trial (aspirin, clopidogrel, and rivaroxaban) were all non-inferior to metoprolol for responder rate in participants with PFO and migraine. Rivaroxaban also showed superior responder rates over metoprolol without an increase in major bleeding events. ClinicalTrials.gov NCT05546320.
Severe tricuspid regurgitation (TR) alters ventricular interaction and left-sided filling dynamics. However, the longitudinal effects of transcatheter tricuspid edge-to-edge repair (T-TEER) on left atrial (LA) remodelling and diastolic physiology remain poorly characterized. We aimed to evaluate longitudinal changes in LA structure, function, and diastolic haemodynamics following T-TEER. We studied 125 consecutive patients undergoing T-TEER within the TRI-FR trial and registry (median age 78 [73-81] years; 60.8% women; 73.6% atrial fibrillation). Comprehensive echocardiography was performed at baseline, pre-discharge, and at 6 and 12 months. Longitudinal changes in LA volume index (LAVI), peak atrial longitudinal strain (PALS), E/e' ratio, LA stiffness index (LASI), and forward flow indices were analysed using linear mixed-effects models. Left atrial volume index decreased immediately after T-TEER (estimated change -8.1 ml/m2; 95% CI -14.6 to -1.6; adjusted P = .033), but this reverse remodelling was not sustained at 12 months. In contrast, LA reservoir function deteriorated early and remained impaired throughout follow-up [PALS -1.2%; 95% confidence interval (CI) -2.0 to -0.3; adjusted P = .029]. Estimated LV filling pressure increased acutely (E/e' + 3.26; 95% CI 2.34-4.18; adjusted P < .001), while LASI remained elevated at 12 months (ratio 1.22; 95% CI 1.05-1.42; adjusted P = .016). Stroke volume index and cardiac index did not change significantly over time (P = .969 and P = .562, respectively). Early mitral regurgitation worsening occurred in 20% of patients but was transient and unrelated to changes in diastolic or forward-flow parameters. Transcatheter tricuspid edge-to-edge repair induces immediate anatomical LA unloading but does not restore LA mechanical function. Despite early reductions in LA volume, filling pressure surrogates increased, LA stiffness remained elevated, and forward flow did not improve. These findings demonstrate a dissociation between structural and functional remodelling after TR correction and highlight the importance of serial assessment of LA mechanics and diastolic physiology following T-TEER.
Enlarged perivascular spaces (EPVSs) in the basal ganglia (BG-EPVS) are an important marker of cerebral small vessel disease (cSVD), and EPVS in the centrum semiovale (CSO-EPVS) are part of the diagnostic criteria for cerebral amyloid angiopathy. We aimed to investigate associations of EPVS with reduced estimated glomerular filtration rate (eGFR) and glomerular hyperfiltration (higher than normal eGFR), which have scarcely been studied previously. In this cross-sectional study, we used pooled individual patient data from the Microbleeds International Collaborative Network which includes patients with ischemic stroke or transient ischemic attack. We investigated associations of impaired kidney function, defined as an eGFR of 30-60 or <30 mL/minute/1.73 m2, and glomerular hyperfiltration, defined as eGFR above the age-adjusted and sex-adjusted 95th centile, with BG-EPVS and CSO-EPVS severity. EPVS were rated according to a validated 5-point ordinal scale, and combined cSVD burden was rated using a validated 5-point ordinal scale with 1 point assigned for the presence of each of the following: severe white matter hyperintensities, ≥1 cerebral microbleed, ≥1 lacune, and BG-EPVS ≥11. Normal glomerular filtration was defined as eGFR ≥60 without hyperfiltration. We used multivariable ordinal logistic regression models to estimate risk of increased EPVS and cSVD burden severity adjusted for age, sex, and comorbidities. Seven thousand two hundred fifty-four patients (mean age 71 ± 13 years, 43% female) were included in the analysis, 357 with glomerular hyperfiltration, 1,692 with eGFR 30-60, and 256 with eGFR <30. Compared with normal glomerular filtration, hyperfiltration was independently associated with BG-EPVS (adjusted odds ratio [aOR] 1.38, 95% CI 1.11-1.70, p < 0.001) and CSO-EPVS (aOR 1.34, 95% CI 1.08-1.64, p = 0.011). Associations of eGFR 30-60 and eGFR <30 with EPVS were not statistically significant. Compared with normal glomerular filtration, eGFR <30 (aOR 1.27, 95% CI 1.03-1.57) was independently associated with increased cSVD burden, but eGFR 30-60 (aOR 1.06, 95% CI 0.95-1.20) and hyperfiltration (aOR 1.15, 95% CI 0.98-1.34) were not. Glomerular hyperfiltration was independently associated with EPVS severity, in both the basal ganglia and centrum semiovale. eGFR <30 was independently associated with total cSVD burden. A key limitation was a lack of repeated eGFR measurements.