Not clinical advice. Clinical Evidence is a current-awareness feed. It is not a clinical decision-support system, not medical advice, and not a substitute for clinical judgment, institutional protocols, or the original sources. Full text, NCCN recommendations, and Cochrane review bodies are not reproduced here.
Specialty
Cardiology
Sources: NEJM, JAMA, Nature, Nature Medicine, Cochrane, JACC. Society hubs are outbound links, not scraped bodies.
Indexed items
Showing 80 of 3422 matching items (19450 indexed).
CochraneSystematic review
The Cochrane database of systematic reviews · Cochrane
BACKGROUND: Hormone therapy is widely provided to control menopausal symptoms and has been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of a Cochrane review first published in 2005.
OBJECTIVES: To assess the long-term effects of prolonged use (at least one year) of hormone therapy on mortality, cardiovascular outcomes, cancer, gallbladder disease, fractures and cognition in perimenopausal and postmenopausal women.
SEARCH METHODS: We used the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, three other databases and two trial registers, together with reference checking, citation searching and contact with study authors to identify the studies included in the review. The latest search date was 26 September 2024.
SELECTION CRITERIA: We included randomised, double-blind trials in which peri- or postmenopausal women took hormone therapy or placebo for at least one year. We included various oestrogen formulations, with or without progestogens. We focused on studies assessing hormone therapy's effects on long-term clinical outcomes, including death, coronary events and cancer. Hormone therapy's efficacy in managing menopausal symptoms was beyond the scope of this review, and is assessed in other Cochrane reviews.
DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias and extracted data. We calculated risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data, along with 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE.
MAIN RESULTS: We included 24 studies - with two newly added in this update - involving 45,660 participants. We derived nearly 70% of the data from two well-conducted studies: the Heart and Estrogen/progestin Replacement Study (HERS 1998) and the large, multi-component Women's Health Initiative research programme, which included two hormone therapy arms (WHI 1998). Across all the studies, most participants were postmenopausal American women with one or more comorbidities. The mean participant age in most studies was over 60 years. Only one included study focused on perimenopausal women. We present full results for all included studies with available data in the main review. The results presented below are drawn from WHI 1998, in which the combined hormone therapy arm and the oestrogen-only arm were run concurrently, with women assigned to the appropriate trial based on their uterus status. One study with 16,608 postmenopausal women with an intact uterus compared combined continuous hormone therapy (conjugated equine oestrogen and medroxyprogesterone acetate) to placebo, and measured outcomes at an average of 5.6 years of follow-up. Based on this study, combined continuous hormone therapy probably makes little to no difference to the risk of a coronary event (RR 1.17, 95% CI 0.95 to 1.44; moderate-certainty evidence). It may increase the risk of stroke (RR 1.39, 95% CI 1.09 to 2.09; low-certainty evidence) and venous thromboembolism (RR 2.03, 95% CI 1.55 to 6.64; low-certainty evidence). Compared to placebo, combined continuous hormone therapy probably increases the risk of breast cancer (RR 1.27, 95% CI 1.03 to 1.56; moderate-certainty evidence) and probably makes little to no difference to the risk of lung cancer (RR 1.06, 95% CI 0.77 to 1.46; moderate-certainty evidence). It may increase gallbladder disease requiring surgery (RR 1.64, 95% CI 1.30 to 2.06; 14,203 participants; low-certainty evidence), and probably reduces the risk of all clinical fractures (RR 0.78, 95% CI 0.71 to 0.86; moderate-certainty evidence). One study including 10,739 postmenopausal women who had undergone a hysterectomy compared oestrogen-only (conjugated equine oestrogen) hormone therapy to placebo, and measured outcomes at an average of seven years' follow-up. Based on this study, oestrogen-only hormone therapy probably makes little to no difference to the risk of coronary events (RR 0.94, 95% CI 0.78 to 1.13), venous thromboembolism (RR 1.32, 95% CI 1.00 to 1.74) and breast cancer (RR 0.79, 95% CI 0.61 to 1.01), all with moderate-certainty evidence. It may make little to no difference to the risk of lung cancer (RR 1.04, 95% CI 0.73 to 1.48; low-certainty evidence). Oestrogen-only hormone therapy probably increases the risk of stroke (RR 1.33, 95% CI 1.06 to 1.67) and gallbladder disease requiring surgery (RR 1.78, 95% CI 1.42 to 2.24), and probably reduces the risk of all clinical fractures (RR 0.73, 95% CI 0.65 to 0.80), all with moderate-certainty evidence. We judged most included studies to have a low risk of bias for most domains. The overall certainty of evidence for the main comparisons was moderate. The main limitation was that only about 30% of women were 50 to 59 years old at baseline, the age group most likely to consider hormone therapy for vasomotor symptoms.
AUTHORS' CONCLUSIONS: Long-term follow-up of women using hormone therapy suggests that the risk profiles vary between combined hormone therapy and oestrogen-only therapy. Oestrogen-only hormone therapy probably makes little to no difference to coronary events, and probably increases the risk of stroke and gallbladder disease. It probably makes little to no difference in the risk of breast cancer, and probably reduces the risk of all fractures. Combined hormone therapy may increase the risk of thromboembolism and probably increases the risk of breast cancer. These results should be interpreted with caution as they are based on one study using oral hormone therapy, which may not represent the risks of the hormone therapy currently used in clinical practice.
AIM: The American College of Cardiology/American Heart Association Scientific Statement, "Clinical Considerations for the Care of the Tactical Athlete With Cardiovascular Abnormalities," was written to provide guidance and education for clinicians caring for the tactical athlete (ie, firefighters, law enforcement officers, military) with cardiovascular disease or risk for cardiovascular disease, and for the organizations overseeing the care and wellness of these athletes. The considerations are shaped by the interaction between occupational demands and fit for full duty assessments, including risk discussions about how a cardiovascular event in a tactical athlete could impact teammates' well-being, community safety, and overall mission success.
METHODS: This scientific statement is organized into 11 sections focused on cardiovascular disease processes and other topics that are relevant when considering the potential risks and benefits of performing tasks specific to the tactical athlete. Task forces, comprised of experts in tactical athlete domains, sports cardiology, and the respective topics covered, were assigned to each section, and specific "Clinical Considerations Tables" for clinicians to reference were prepared. Comprehensive literature reviews and an emphasis on tactical athlete-focused data, as available, were integral in the writing of all clinical considerations presented. The framework mirrors that of the recently published, "Clinical Considerations for Competitive Sports Participation for Athletes With Cardiovascular Abnormalities: A Scientific Statement From the American Heart Association and American College of Cardiology."
STRUCTURE: The specific sections in this document include: Section 1: Tactical Tasks Classification; Section 2: The Tactical Athlete Preparticipation Cardiac Evaluation; Section 3: Ethical and Legal Aspects of Tactical Clinical Management; Section 4: Genetic Cardiomyopathies; Section 5: Myocarditis and Other Acquired Cardiac Conditions; Section 6: Congenital Heart Disease; Section 7: Aortopathy, Bicuspid Aortic Valve, and Spontaneous Coronary Artery Dissection; Section 8: Syncope, SCA, Arrhythmias, and Devices; Section 9: Cardiac Channelopathies; Section 10: Older Tactical Athlete; Section 11: Environmental Exposures, PED/S, and Additional Cardiac Conditions and Considerations. Each section provides a summary detailing the rationale for key clinical considerations and the respective Clinical Considerations Table(s).
BACKGROUND: Magnesium sulphate is a common therapy in perinatal care. Its benefits when given to women at risk of preterm birth for fetal neuroprotection (prevention of cerebral palsy for children) were shown in a 2009 Cochrane review. Internationally, use of magnesium sulphate for preterm cerebral palsy prevention is now recommended practice. As new randomised controlled trials (RCTs) and longer-term follow-up of prior RCTs have since been conducted, this review updates the previously published version.
OBJECTIVES: To assess the effectiveness and safety of magnesium sulphate as a fetal neuroprotective agent when given to women considered to be at risk of preterm birth.
SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 17 March 2023, as well as reference lists of retrieved studies.
SELECTION CRITERIA: We included RCTs and cluster-RCTs of women at risk of preterm birth that assessed prenatal magnesium sulphate for fetal neuroprotection compared with placebo or no treatment. All methods of administration (intravenous, intramuscular, and oral) were eligible. We did not include studies where magnesium sulphate was used with the primary aim of preterm labour tocolysis, or the prevention and/or treatment of eclampsia.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed RCTs for inclusion, extracted data, and assessed risk of bias and trustworthiness. Dichotomous data were presented as summary risk ratios (RR) with 95% confidence intervals (CI), and continuous data were presented as mean differences with 95% CI. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS: We included six RCTs (5917 women and their 6759 fetuses alive at randomisation). All RCTs were conducted in high-income countries. The RCTs compared magnesium sulphate with placebo in women at risk of preterm birth at less than 34 weeks' gestation; however, treatment regimens and inclusion/exclusion criteria varied. Though the RCTs were at an overall low risk of bias, the certainty of evidence ranged from high to very low, due to concerns regarding study limitations, imprecision, and inconsistency. Primary outcomes for infants/children: Up to two years' corrected age, magnesium sulphate compared with placebo reduced cerebral palsy (RR 0.71, 95% CI 0.57 to 0.89; 6 RCTs, 6107 children; number needed to treat for additional beneficial outcome (NNTB) 60, 95% CI 41 to 158) and death or cerebral palsy (RR 0.87, 95% CI 0.77 to 0.98; 6 RCTs, 6481 children; NNTB 56, 95% CI 32 to 363) (both high-certainty evidence). Magnesium sulphate probably resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.96, 95% CI 0.82 to 1.13; 6 RCTs, 6759 children); major neurodevelopmental disability (RR 1.09, 95% CI 0.83 to 1.44; 1 RCT, 987 children); or death or major neurodevelopmental disability (RR 0.95, 95% CI 0.85 to 1.07; 3 RCTs, 4279 children) (all moderate-certainty evidence). At early school age, magnesium sulphate may have resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.82, 95% CI 0.66 to 1.02; 2 RCTs, 1758 children); cerebral palsy (RR 0.99, 95% CI 0.69 to 1.41; 2 RCTs, 1038 children); death or cerebral palsy (RR 0.90, 95% CI 0.67 to 1.20; 1 RCT, 503 children); and death or major neurodevelopmental disability (RR 0.81, 95% CI 0.59 to 1.12; 1 RCT, 503 children) (all low-certainty evidence). Magnesium sulphate may also have resulted in little to no difference in major neurodevelopmental disability, but the evidence is very uncertain (average RR 0.92, 95% CI 0.53 to 1.62; 2 RCTs, 940 children; very low-certainty evidence). Secondary outcomes for infants/children: Magnesium sulphate probably resulted in little to no difference in severe intraventricular haemorrhage (grade 3 or 4) (RR 0.81, 95% CI 0.64 to 1.04; 6 RCTs, 6542 infants; moderate-certainty evidence) and may have resulted in little to no difference in chronic lung disease/bronchopulmonary dysplasia (average RR 0.92, 95% CI 0.77 to 1.10; 5 RCTs, 6689 infants; low-certainty evidence). Primary outcomes for women: Magnesium sulphate may have resulted in little or no difference in severe maternal outcomes potentially related to treatment (death, cardiac arrest, respiratory arrest) (RR 0.32, 95% CI 0.01 to 7.92; 4 RCTs, 5300 women; low-certainty evidence). However, magnesium sulphate probably increased maternal adverse effects severe enough to stop treatment (average RR 3.21, 95% CI 1.88 to 5.48; 3 RCTs, 4736 women; moderate-certainty evidence). Secondary outcomes for women: Magnesium sulphate probably resulted in little to no difference in caesarean section (RR 0.96, 95% CI 0.91 to 1.02; 5 RCTs, 5861 women) and postpartum haemorrhage (RR 0.94, 95% CI 0.80 to 1.09; 2 RCTs, 2495 women) (both moderate-certainty evidence). Breastfeeding at hospital discharge and women's views of treatment were not reported.
AUTHORS' CONCLUSIONS: The currently available evidence indicates that magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus, compared with placebo, reduces cerebral palsy, and death or cerebral palsy, in children up to two years' corrected age. Magnesium sulphate may result in little to no difference in outcomes in children at school age. While magnesium sulphate may result in little to no difference in severe maternal outcomes (death, cardiac arrest, respiratory arrest), it probably increases maternal adverse effects severe enough to stop treatment. Further research is needed on the longer-term benefits and harms for children, into adolescence and adulthood. Additional studies to determine variation in effects by characteristics of women treated and magnesium sulphate regimens used, along with the generalisability of findings to low- and middle-income countries, should be considered.
BACKGROUND: Extreme temperature events are projected to increase with climate change; yet, associations of short-term heat and cold exposure with heart failure (HF) exacerbations remain incompletely characterized, especially in high-latitude settings.
OBJECTIVES: The purpose of this study was to investigate the associations of short-term exposure to cold spells, heat waves, and nonoptimal ambient temperature with HF hospitalization in Sweden.
METHODS: We conducted a nationwide time-stratified case-crossover study including 482,000 HF hospitalizations recorded in the Swedish National Patient Register (2006-2021). Cold spells and heat waves were defined as ≥2 consecutive days with daily mean temperature ≤5th percentile (October to March) or ≥95th percentile (April to September), respectively, using municipality-specific temperature distributions. We applied conditional logistic regression combined with distributed lag nonlinear models to estimate lag-specific (lag 0-6 days) and cumulative associations with the odds of HF hospitalization.
RESULTS: During the cold season, cold spells and lower ambient temperature exposures were associated with a higher risk of HF hospitalization at lag 2 to 6 days (significant at lag 3-5 days). Cumulative associations over lag 2 to 6 days showed ORs of 1.085 (95% CI: 1.042-1.129) for cold spells and 1.008 (95% CI: 1.005-1.011) per 10-percentile-point decrease in temperature. During the warm season, higher temperature exposure was associated with higher odds at lag 1 to 3 days with attenuation at longer lags, with a cumulative association over lag 0 to 3 days (OR: 1.009; 95% CI: 1.006-1.013, per 10-percentile-point increase in temperature). Heat waves showed nonsignificant positive associations with HF hospitalizations that were more likely to capture acute exacerbations, whereas no associations were observed using the broader HF definition that included chronic conditions.
CONCLUSIONS: In this Swedish nationwide study, short-term exposure to cold spells, lower temperatures, and higher temperatures was associated with a higher risk of HF hospitalization, with delayed cold effects and more immediate heat effects.
IMPORTANCE: SARS-CoV-2 remains a substantial cause of respiratory illness, morbidity, and mortality. Evidence to date has demonstrated that COVID-19 vaccines reduce the risk of severe disease, including hospitalization and death.
OBJECTIVE: This systematic review identifies and summarizes newly published studies reporting on the effectiveness and safety of COVID-19 vaccines and COVID-19 epidemiology in the US.
EVIDENCE REVIEW: Cochrane Central Register of Controlled Trials, PubMed/MEDLINE, Embase, and Scopus were searched from August 1, 2025, through June 29, 2026. Studies were eligible if they reported on the effectiveness, efficacy, or safety of a US-licensed COVID-19 vaccine or SARS-CoV-2 epidemiology in the US.
FINDINGS: From 11 829 identified references, 155 publications were eligible (15 randomized clinical trials, 84 observational studies with a comparator group, 38 product safety studies without a comparator group [single group], and 18 descriptive studies of disease burden). Consistent with prior evidence, studies reported that updated COVID-19 vaccines were associated with a reduction in the risk of hospitalization among both older adults (≥65 years; vaccine effectiveness [VE], 53.0%; 95% CI, 37.0%-65.0%; 2025-2026 season) and adults (18-64 years; VE, 54.0%; 95% CI, 1.0%-78.0%; 2024-2025 season). Maternal vaccination was associated with reduced risk of COVID-19-associated emergency department/urgent care encounters among individuals vaccinated (VE, 58.0%; 95% CI, 24.0%-77.0%) and with fewer COVID-19-related hospital contacts in the first 2 months of life among infants born subsequently (VE range, 50.0%-54.0%), regardless of trimester of vaccination. Vaccination was also associated with a significant reduction in COVID-19-related pediatric emergency department visits (9 months to 4 years; VE, 76.0%; 95% CI, 58.0%-87.0%). Vaccination was associated with a reduced risk of critical COVID-19 illness (intensive care unit admission or death) in immunocompromised adults (VE range, 32.0%-53.0%, depending on condition and other factors). Health care personnel who received 3 to 5 vaccine doses were less likely to develop laboratory-confirmed COVID-19 illness (VE, 41.0%; 95% CI, 34.0%-47.0%) and postacute COVID-19 symptoms (VE, 57.0%; 95% CI, 46.0%-66.0%) compared with those who received only 2 doses. Across adverse events of special interest (eg, stroke, thrombosis, myocarditis), safety profiles were consistent with those of previous reviews. No identified studies conducted under the updated guidance on extended dosing intervals for the primary series reported an increased risk of myocarditis or pericarditis. No new safety signals were reported in the recently published studies eligible for this updated review of US-licensed COVID-19 vaccines.
CONCLUSIONS AND RELEVANCE: COVID-19 vaccines were consistently associated with a reduction in the risk of hospitalization and other outcomes, including among individuals at high risk of severe COVID-19, such as infants, and those who were pregnant. No new safety concerns were identified.
Neurodegeneration is a major driver of disability in multiple sclerosis (MS), the most common chronic inflammatory disease of the central nervous system (CNS). Retinal ganglion cells (RGCs), a heterogeneous neuronal population in the eye, undergo degeneration in MS and provide a model to study neuronal subtype-specific resilience to inflammatory injury. However, the neuron-intrinsic mechanisms underlying differential vulnerability remain unclear. Here we identify a neuroprotective role for intracellular complement factor H (CFH) in neurons. Using single-nucleus RNA-sequencing analysis of RGCs from donors with MS and control individuals, we found that CFH expression was strongly correlated with intrinsic resilience to RGC degeneration. Mechanistically, CFH was induced in retinal and other CNS neurons in response to inflammatory and oxidative stress, where it limited reactive oxygen species accumulation and lipid peroxidation. CFH localized to the endoplasmic reticulum, a major site of lipid peroxidation during neuronal ferroptosis. Its protective activity was dependent on its C-terminal SCR20 domain, was independent of CFH secretion and was preserved in the absence of complement component C3. These findings reveal a non-canonical intracellular function of CFH in neurons. Together, our results identify CFH as a key mediator of neuronal resilience across the CNS in mice and humans and provide mechanistic insight into inflammatory neurodegeneration with implications for MS therapy and neuroprotection more broadly.
Metabolic dysfunction-associated steatotic liver disease (MASLD), including its progressive form metabolic dysfunction-associated steatohepatitis (MASH), represents the hepatic manifestation of metabolic syndrome and is increasingly recognized as a multi-organ disease. MASLD is now the most prevalent chronic liver disease worldwide and a rising indication for liver transplantation. MASLD incidence continues to increase, driven by sedentary lifestyles, the obesity epidemic and associated pathologies such as type 2 diabetes. MASH is a significant risk factor for fibrosis, cirrhosis and hepatocellular carcinoma (HCC)-a leading cause of cancer-related death. Over the past decade, substantial progress has been made in elucidating the molecular and cellular mechanisms driving MASLD initiation and progression. Key pathogenic processes include insulin resistance, genetic drivers, dysregulated hepatic lipid metabolism, lipotoxicity, adipose tissue dysfunction, immune-mediated inflammation, fibrogenesis and perturbations of the gut-liver axis. Increasingly, these mechanistic insights are informing clinical translation. Genetic risk variants and polygenic risk scores are beginning to enable improved risk stratification for disease progression and HCC. Furthermore, therapeutic strategies targeting defined metabolic pathways are emerging, including approaches that reduce hepatic lipogenesis or modulate mitochondrial metabolism. Here we highlight the state of the art of molecular and cellular mechanisms underlying MASH pathogenesis and its transition to HCC.
Nature, Published online: 01 September 2026; doi:10.1038/d41586-026-02740-w Small trial targeted liver proteins that play a part in the regulation of lipid levels.
This trial examined whether starting dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, 1 day prior to elective cardiac surgery reduces the risk of acute kidney injury (AKI) in the week following surgery compared with placebo.
In the Original Investigation titled “Global and Domain-Specific Cognitive Outcomes After Catheter Ablation for Atrial Fibrillation,” published July 31, 2026, Drs Triantafyllou's and Bakogiannis’s first names were misspelled in the byline. The article has been corrected.
OBJECTIVE: To characterize the salivary microbiome of patients with laryngopharyngeal reflux disease (LPRD) and investigate its associations with clinical presentation and salivary gastroduodenal enzymes.
STUDY DESIGN: Prospective controlled study.
SETTING: University Hospital.
METHODS: Saliva samples from patients with LPRD at the 24-hour hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing and asymptomatic individuals were consecutively collected for analyzing digestive enzyme/biomarker (pepsin, elastase, bile salts, cholesterol, trypsin) and microbiome features (16S rRNA IlluminaMiSeq). Pretreatment to posttreatment symptoms and findings were evaluated with reflux symptom score and reflux sign assessment. Association between microbiome abundance, enzyme concentration, and baseline and post-treatment clinical findings were assessed.
RESULTS: Sixty-seven LPRD patients (40 females [59.7%]) and 44 controls (26 females [59.1%]) completed the evaluations. LPRD patients demonstrated significantly higher concentrations of elastase, higher salivary pH, and lower levels of cholesterol compared to controls. The comparative analysis of salivary microbiota between LPRD patients and controls demonstrated significant taxonomic-level alterations in alpha diversity (reduced Shannon index at family and genus levels in LPRD, P < .006) and beta diversity (distinct community composition by UniFrac metrics, PERMANOVA, P ≤ .005), with differential abundance of key taxa including a modulation of Streptococcus species, elevated Actinomyces and Abiotrophia, and depleted Oribacterium and Eubacterium nodatum group in LPRD patients compared to controls. Elastase, trypsin, and bile salts reported significant association with relative abundance of some bacteria.
CONCLUSION: This preliminary study supports that LPRD patients exhibit distinct microbial signatures compared to asymptomatic subjects, characterized by reduced diversity at specific taxonomic levels, subtle shifts in community membership, and differential abundance of some key genera.
IMPORTANCE: Although modern radiotherapy (RT) techniques have reduced cardiac exposure, concerns regarding RT-induced heart disease persist. Identifying which patients are most vulnerable to cardiac toxic effects is crucial for personalized survivorship care.
OBJECTIVE: To evaluate whether the association between tumor laterality and ischemic heart disease (IHD) risk varies by cumulative baseline cardiovascular risk burden.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective nationwide cohort study used data on 23 305 women in the Korean National Health Insurance Service database who underwent postoperative RT for breast cancer without prior IHD from January 1, 2002, to December 31, 2018. The median follow-up was 4.3 years (IQR, 2.5-6.5 years); data analysis was completed in March 2023.
EXPOSURES: Treatment laterality (left-sided vs right-sided RT) and baseline cardiovascular risk burden (defined as a count of 6 factors: age ≥55 years, obesity, smoking, hypertension, diabetes, and dyslipidemia).
MAIN OUTCOMES AND MEASURES: The cumulative incidence of IHD was estimated using competing-risk analysis. Subdistribution hazard ratios (sHRs) were calculated using Fine-Gray models.
RESULTS: Of 23 305 patients (mean [SD] age, 51.7 [9.2] years), 11 723 (50.3%) received left-sided RT and 11 582 (49.7%) received right-sided RT. Left-sided RT was associated with a statistically significant increase in IHD risk (sHR, 1.11; 95% CI, 1.01-1.22; P = .04). No statistically significant difference in IHD risk between left- and right-sided RT was observed among patients with 0 to 2 cardiovascular risk factors, whereas left-sided RT was associated with significantly higher IHD risk among patients with 3 risk factors (adjusted sHR, 1.37; 95% CI, 1.10-1.71; Gray test P = .004).
CONCLUSIONS AND RELEVANCE: In this cohort study of 23 305 women with breast cancer, excess cardiac risk associated with left-sided RT was concentrated among patients with 3 cardiovascular risk factors. These findings suggest that among patients with low baseline risk profiles, the difference in IHD risk between left- and right-sided treatment may be small, whereas those with high cardiovascular burden warrant prioritized access to advanced heart-sparing modalities and aggressive risk factor management.
This trial evaluated whether mechanical thrombectomy—removal of a blood clot by catheter—in addition to usual medical treatment improved outcomes for patients with acute ischemic stroke (AIS) caused by a medium or distal arterial blockage.
IMPORTANCE: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impact exposure. CTE can only be diagnosed post mortem, and the antemortem neuropsychological profile is poorly understood, hindering accurate diagnosis before death.
OBJECTIVE: To characterize antemortem neuropsychological test performance of former National Football League (NFL) players with autopsy-confirmed CTE.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective case series included former NFL players who completed an antemortem neuropsychological evaluation and had autopsy-confirmed CTE. Data were collected between January 1, 2017, and April 30, 2025. Statistical analysis was performed from September 2025 to June 2026.
EXPOSURE: CTE neuropathology, defined by the National Institute of Neurological Disorders and Stroke/National Institute of Biomedical Imaging and Bioengineering consensus panel.
MAIN OUTCOMES AND MEASURES: Neuropsychological test performance, neuropathologic diagnoses, and semiquantitative phosphorylated tau (p-tau) pathology across 11 brain regions were examined. Raw scores were converted to z scores using age, sex, and/or education level-based normative data. Test results with z scores of -1.5 or less were categorized as impaired; domains with 2 or more impaired test results were considered impaired.
RESULTS: The primary analytic sample included 33 men (mean [SD] age at death, 65.4 [13.3] years; mean [SD] time between testing and death, 2.4 [1.6] years), 25 with high- and 8 with low-stage CTE. Learning and memory was most impaired (17 of 27 [63.0%]), followed by executive function (15 of 29 [51.7%]) and language (12 of 29 [41.4%]). High-stage CTE participants generally had worse scores than low-stage CTE participants. Greater global p-tau burden was associated with worse learning and memory performance (B = -0.40; 95% CI, -0.70 to -0.09; P = .01). Findings were similar after excluding 9 participants with co-occurring Alzheimer disease or frontotemporal lobar degeneration tau.
CONCLUSIONS AND RELEVANCE: In this retrospective case series of NFL players with autopsy-confirmed CTE, memory, executive function, and language impairments were common, and p-tau burden was associated with worse memory performance. Findings provide insight into the expected CTE neuropsychological profile and may help advance diagnosis before death.
IMPORTANCE: The burden of cardiogenic out-of-hospital cardiac arrest (OHCA) among older adults is increasing. No-flow time is a key determinant of prognosis, and the aging brain may be increasingly vulnerable to ischemic injury during this interval.
OBJECTIVE: To delineate the association between no-flow duration and outcomes in older adults with cardiogenic OHCA using dynamic probability curves.
DESIGN, SETTING, AND PARTICIPANTS: This nationwide, population-based, multicenter retrospective observational cohort study used data from the All-Japan Utstein Registry from January 1, 2010, through December 31, 2023. Participants included adults 65 years or older with witnessed cardiogenic OHCAs treated within Japan's nationwide emergency medical service (EMS) system. Data were analyzed from December 1, 2025, to July 7, 2026.
EXPOSURE: No-flow time, defined as the interval from witnessed arrest to initiation of cardiopulmonary resuscitation by EMS clinicians.
MAIN OUTCOMES AND MEASURES: The primary outcome was 30-day favorable neurologic outcome, defined as cerebral performance category of 1 or 2. Age-stratified dynamic probability curves were constructed for patients aged 65 to 74 years, 75 to 84 years, 85 to 94 years, and 95 years or older to describe the time-dependent likelihood of outcome according to no-flow duration. For each age group, the no-flow time at which the estimated probability fell below 1% with 95% CIs was identified.
RESULTS: Among 1 795 502 registry cases, 259 851 patients met the inclusion criteria. The median patient age was 82 (IQR, 75-88) years, 148 018 (57.0%) were male, and the median no-flow time was 11 (IQR, 8-15) minutes. Overall, 8711 patients (3.4%) achieved a 30-day favorable neurologic outcome. In all patients 65 years or older, the no-flow times at which the estimated probability of favorable neurologic outcome fell below 1% was 11 (95% CI, 11-11) minutes. Corresponding thresholds for favorable neurologic outcome was 14 (95% CI, 14-14) minutes for those aged 65 to 74 years, 11 (95% CI, 10-11) minutes for those aged 75 to 84 years, 2 (IQR, 0-4) minutes for those aged 85 to 94 years, and 0 (95% CI, 0-0) minutes for those 95 years or older.
CONCLUSIONS AND RELEVANCE: In this cohort study of older adults with cardiogenic OHCA, the no-flow time window compatible with an estimated probability of at least 1% for favorable neurologic outcome became progressively shorter with advancing age. These findings may inform resuscitation decision-making in aging populations.
IMPORTANCE: The net benefit of oral anticoagulants (OACs) in patients with atrial fibrillation (AF) and advanced chronic kidney disease (CKD) not receiving dialysis remains uncertain.
OBJECTIVE: To compare the estimated effectiveness and safety of apixaban compared with warfarin and no OAC use among patients with AF and advanced CKD not receiving dialysis.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used a 3-group target trial emulation framework and included patients from Medicare fee-for-service claims (January 1, 2013, to December 31, 2022) and the Optum deidentified Clinformatics Data Mart database (January 1, 2013, to February 28, 2025). Eligible participants had AF, CKD stage 4 or 5, no prior dialysis, and continuous medical and pharmacy coverage. Data analysis was conducted from February 2025 to June 2026.
EXPOSURES: Initiation of apixaban or warfarin vs no oral anticoagulation.
MAIN OUTCOMES AND MEASURES: Primary outcomes were hospitalization for major bleeding, ischemic stroke, and their composite. Propensity score matching weights were used to balance baseline characteristics, and weighted hazard ratios (HRs) and rate differences (RDs) per 1000 person-years (PYs) were estimated.
RESULTS: The study included 14 712 apixaban users (7954 female [54.1%]; mean [SD] age, 78.93 [7.35] years), 6335 warfarin users (3148 female [49.7%]; mean [SD] age, 77.47 [7.03] years), and 21 005 nonusers of OACs (10 797 female [51.4%]; mean [SD] age, 79.59 [7.49] years). Compared with nonusers, apixaban was associated with an increased rate of major bleeding (HR, 1.32 [95% CI, 1.11 to 1.58]; RD, 17.16 [95% CI, 2.45 to 31.87] per 1000 PYs) and a lower rate of ischemic stroke (HR, 0.46 [95% CI, 0.32 to 0.66]; RD, -12.67 [95% CI, -20.65 to -4.69] per 1000 PYs), but there was no association with the composite outcome (HR, 1.05 [95% CI, 0.89 to 1.22]; RD, 6.13 [95% CI, -10.61 to 22.87] per 1000 PYs). Warfarin users had a higher rate of major bleeding (HR, 2.44 [95% CI, 2.06 to 2.88]) and no significant diffrence in the rate of ischemic stroke (HR, 0.87 [95% CI, 0.61 to 1.22]), resulting in a higher rate of the composite outcome compared with nonuse (HR, 1.95 [95% CI, 1.69 to 2.26]). Compared with warfarin, apixaban was associated with lower risk of major bleeding (HR, 0.55 [95% CI, 0.46 to 0.65]) and ischemic stroke (HR, 0.50 [95% CI, 0.33 to 0.78]).
CONCLUSIONS AND RELEVANCE: This study found that among patients with AF and advanced CKD not receiving dialysis, anticoagulation was associated with reduced risk of ischemic stroke, but increased risk of bleeding compared with nonuse, suggesting that the trade-off between ischemic stroke reduction and bleeding risk was more favorable for apixaban than for warfarin.
IMPORTANCE: Perioperative interruption of vitamin K antagonist (VKA) therapy in patients with mechanical heart valves (MHVs) is complex, and contemporary data to inform management are limited.
OBJECTIVES: To describe perioperative anticoagulation management and to estimate 30-day risks of arterial thromboembolism (ATE) and bleeding after VKA interruption in adults with left-sided MHVs.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included consecutive adult patients (aged ≥18 years) with left-sided aortic, mitral, or dual MHVs undergoing planned invasive procedures requiring VKA interruption from January 1, 2016, to December 31, 2023, with 30-day follow-up. The study was conducted at the thrombosis clinic at The Ottawa Hospital in Ontario, Canada.
EXPOSURE: Planned invasive procedure requiring temporary interruption of VKA therapy.
MAIN OUTCOMES AND MEASURES: Primary outcomes were 30-day postoperative ATE and major bleeding. Secondary outcomes included clinically relevant nonmajor bleeding (CRNMB) and all-cause mortality. Major bleeding and CRNMB were defined according to the International Society on Thrombosis and Hemostasis.
RESULTS: The cohort included 373 patients (median [IQR] age, 67 [60-73] years; 217 [58.2%] male) contributing 613 interruptions. Therapeutic-dose bridging was used preoperatively in 516 interruptions (84.2%) and postoperatively in 193 (31.5%) (99 of 215 [46.0%] in mitral or dual MHV vs 94 of 398 [23.6%] in aortic MHV interruptions). Patients with mitral or dual (vs aortic) valve position and prior thromboembolism had higher estimated odds of receiving postoperative therapeutic-dose bridging (mitral or dual vs aortic: adjusted odds ratio [aOR], 2.90; 95% CI, 1.91-4.41; prior thromboembolism: aOR, 1.91; 95% CI, 1.05-3.46). Estimated 30-day risks of ATE and major bleeding were 1.5% (95% CI, 0.8%-2.8%) and 2.1% (95% CI, 1.2%-3.6%), respectively. Clinically relevant bleeding (composite of major bleeding and CRNMB) occurred in 3.9% (95% CI, 2.6%-5.8%) of interruptions. Three deaths occurred (0.5%; 95% CI, 0.2%-1.5%), 1 attributed to fatal ischemic stroke. Omission of postoperative bridging was associated with higher estimated ATE risk (4.9% vs 0.9%; subdistribution hazard ratio [sHR], 5.30; 95% CI, 1.45-19.40; P = .01); this finding was no longer statistically significant in landmark analysis (sHR, 3.26; 95% CI, 0.62-17.21).
CONCLUSIONS AND RELEVANCE: In this retrospective cohort study, patients with MHVs experienced clinically meaningful risks of perioperative ATE and bleeding. These data do not establish a causal protective effect of postoperative bridging. However, omitting bridging in patients with MHVs was associated with a higher estimated risk of ATE in exploratory analyses and should be approached cautiously, pending stronger evidence from representative cohorts.
BACKGROUND: Whether catheter-directed thrombolysis improves clinical outcomes in patients with intermediate-high-risk pulmonary embolism, as compared with anticoagulation alone, is uncertain.
METHODS: In this multicenter, open-label, randomized trial, we randomly assigned patients with intermediate-high-risk acute pulmonary embolism (defined by hemodynamic stability, a simplified Pulmonary Embolism Severity Index score of ≥1, and right ventricular dysfunction plus an elevated level of cardiac troponin or natriuretic peptide) in a 1:1 ratio to receive catheter-directed thrombolysis with alteplase plus anticoagulation therapy (thrombolysis group) or anticoagulation therapy alone (standard-care group). The primary outcome was a composite of death from any cause, recurrence of pulmonary embolism, or cardiorespiratory decompensation or collapse within 7 days after randomization. Secondary outcomes included clinically relevant bleeding as defined by the Bleeding Academic Research Consortium, major bleeding as defined in the Global Use of Strategies to Open Occluded Coronary Arteries guidelines, and intracranial hemorrhage.
RESULTS: A total of 558 patients underwent randomization; 280 were assigned to the thrombolysis group, and 278 to the standard-care group. The median age was 64 years, and 40.9% were female. A primary-outcome event occurred in 2 patients (0.7%) in the thrombolysis group and in 19 patients (6.8%) in the standard-care group (relative risk, 0.10; 95% confidence interval, 0.02 to 0.44; P<0.001); this difference was driven mainly by the lower incidence of cardiorespiratory decompensation or collapse in the thrombolysis group. By day 7, clinically relevant bleeding had occurred in 13 patients (4.6%) in the thrombolysis group and in 14 patients (5.0%) in the standard-care group (P = 0.85); major bleeding in 4 (1.4%) and 6 (2.2%), respectively (P = 0.54); and intracranial hemorrhage in 2 (0.7%) and none. One patient in the thrombolysis group died within 30 days, and 4 patients in the standard-care group died within 7 days.
CONCLUSIONS: Among patients with intermediate-high-risk acute pulmonary embolism, catheter-directed thrombolysis with alteplase plus anticoagulation therapy led to a lower risk of death from any cause, recurrent pulmonary embolism, or cardiorespiratory decompensation or collapse within 7 days after randomization than anticoagulation therapy alone. (Funded by the Ministry of Health of the Czech Republic and others; PRAGUE-26 ClinicalTrials.gov number, NCT05493163; EudraCT number, 2022-002218-18; European Union Clinical Trials number, 2024-516144-25-00.).
BACKGROUND: Lipoprotein(a) [Lp(a)] is a largely genetically determined causal risk factor for atherosclerotic cardiovascular disease and aortic stenosis, likely mediated in part by oxidized phospholipids (OxPL) bound to apolipoprotein(a) [apo(a)] and apolipoprotein B (apoB). Lepodisiran, an extended-duration small interfering RNA demonstrated large and durable reductions in Lp(a) in a phase 2 trial.
OBJECTIVES: The purpose of this study was to assess effects of lepodisiran on OxPL-apo(a) and -apoB levels, their relationship to Lp(a) and apoB lowering, whether reductions are proportional to particle reduction, and whether changes correlate with biomarkers of systemic inflammation.
METHODS: The randomized, placebo-controlled phase 2 trial enrolled 320 participants at 66 global centers. The current post hoc analysis included 213 of 320 participants who received placebo or lepodisiran 16, 96, or 400 mg at baseline and day 180 and had OxPL levels measured at baseline, day 240, and day 360. Placebo-adjusted percent change from baseline in OxPL-apo(a) and -apoB were assessed. Correlations between percent change in Lp(a), OxPL-apo(a), and -apoB were also determined.
RESULTS: Median baseline OxPL-apo(a) and -apoB levels were 122.0 nmol/L (Q1, Q3: 105.1, 137.7 nmol/L) and 27.7 nmol/L (Q1, Q3: 22.5, 36.2 nmol/L) for all participants. Placebo-adjusted geometric mean percent changes in OxPL-apo(a) at day 240 were -21.9% (95% CI: -45.0% to 11.0%), -65.1% (95% CI: -73.8% to -53.6%), and -94.2% (95% CI: -95.7% to -92.2%) in the 16-, 96-, and 400-mg dose groups, respectively. Percent changes in OxPL-apoB at day 240 in these dose groups were -39.5% (95% CI: -51.2% to -25.0%), -76.9% (95% CI: -80.6% to -72.5%), and -88.5% (95% CI: -90.4% to -86.3%), respectively. The percent change in OxPL-apo(a) at day 360 were -23.7% (95% CI: -47.0% to 9.8%), -41.6% (95% CI: -56.4% to -21.6%), and -80.7% (95% CI: -85.7% to -73.9%) in the 16-, 96-, and 400-mg dose groups, respectively. The percent changes in OxPL-apoB at day 360 in these dose groups were -30.6% (95% CI: -46.4% to -10.2%), -57.1% (95% CI: -65.2% to -47.2%), and -79.9% (95% CI: -83.8% to -75.2%), respectively. Percent change in OxPL-apo(a) correlated more closely than OxPL-apoB with percent change in Lp(a) than did OxPL-apoB. There was no significant correlation between changes in high-sensitivity C-reactive protein and OxPL.
CONCLUSIONS: Lepodisiran produced sustained reductions in OxPL-apoB and OxPL-apo(a) levels that correlated with Lp(a) lowering. These findings provide additional biological rationale for the ongoing lepodisiran phase 3 cardiovascular outcomes trial, but do not establish clinical benefit. (A Study of LY3819469 in Participants With Elevated Lipoprotein(a) [Lp(a)]; NCT05565742).
BACKGROUND: In patients with syncope who present to the emergency department for evaluation, diagnosing an underlying cardiac arrhythmia remains difficult.
METHODS: We conducted an open-label, randomized, controlled trial at 45 hospitals in the United Kingdom to assess the effects of 14-day cardiac monitoring on diagnosis, treatment, and outcomes among patients with syncope. Adults with syncope that remained unexplained after an evaluation in the emergency department were assigned in a 1:1 ratio to undergo 14-day ambulatory electrocardiographic (ECG) monitoring (the intervention group) or to receive the standard care provided for patients with unexplained syncope at each participating site (the standard-care group). The primary outcome was the mean number of patient-reported episodes of syncope at 1 year.
RESULTS: A total of 2234 patients underwent randomization: 1123 were assigned to the intervention group and 1111 to the standard-care group. The mean age of the patients was 58.3 years, and 52.1% were male. After the exclusion of patients who did not complete any follow-up, a total of 1970 patients (1004 in the intervention group and 966 in the standard-care group) were included in the primary analysis. The mean (±SD) number of patient-reported syncope episodes at 1 year was 1.37±5.10 in the intervention group and 1.58±8.56 in the standard-care group (incidence rate ratio, 0.89; 95% confidence interval, 0.68 to 1.18; P = 0.42). A total of 49 adverse events were reported in the intervention group, and 8 adverse events were reported in the standard-care group, with 1 serious adverse event in each group.
CONCLUSIONS: Among patients with syncope that remained unexplained after evaluation in the emergency department, the use of 14-day ambulatory ECG monitoring did not result in significantly fewer patient-reported syncope episodes at 1 year than standard care. (Funded by the British Heart Foundation and National Health Service Research Scotland; ASPIRED ISRCTN Registry number, ISRCTN10278811.).
BACKGROUND: Although guideline-recommended intensive lipid-lowering therapy (LLT) reduces recurrent cardiovascular events after acute coronary syndrome (ACS), timely implementation of intensive LLT and achievement of low-density lipoprotein cholesterol (LDL-C) target remain suboptimal in routine clinical practice.
OBJECTIVES: The purpose of this study was to determine whether a protocol-based implementation strategy improves timely achievement of guideline-recommended LDL-C target after ACS.
METHODS: We conducted a cluster-randomized trial involving patients with ACS. Ten centers were randomly assigned 1:1 to protocol-based or standard lipid management. In the protocol-based group, LLT was initiated or intensified during the index hospitalization according to a prespecified algorithm based on baseline LLT status and LDL-C levels using high-intensity statins, ezetimibe, and PCSK9 inhibitors. LDL-C was reassessed at 4 weeks, with treatment escalation when indicated. In the protocol-based group, an LDL-C level of approximately 55 mg/dL was used as the protocol-specified operational threshold for intensification, whereas LDL-C <70 mg/dL was the treatment goal in both groups. The primary and key secondary endpoints were achievement of LDL-C <70 mg/dL and <55 mg/dL at 6 months, respectively.
RESULTS: Between November 2024 and July 2025, 330 patients were enrolled, and 329 patients comprised the study population after 1 patient withdrew consent. The primary efficacy analysis included 315 patients with complete 6-month LDL-C data. Baseline characteristics were balanced between groups. The mean age was 69 years, 18% were women, and the median LDL-C level was 110 mg/dL. At 6 months, LDL-C <70 mg/dL was achieved in 86.4% vs 73.7% (between-group difference, 12.6 percentage points [95% CI: 3.8-21.5 percentage points]; P = 0.005); the corresponding difference was 12.8 percentage points (95% CI: -2.0 to 27.6 percentage points; P = 0.08) in a hospital-level sensitivity analysis. Similar findings were observed for LDL-C <55 mg/dL (60.8% vs 34.5%; between-group difference, 26.3 percentage points [95% CI: 18.5-34.0 percentage points]; P < 0.001). At 6 months, use of high-intensity statins, ezetimibe, and PCSK9 inhibitors was higher in the protocol-based group.
CONCLUSIONS: A protocol-based implementation strategy for early intensive LLT significantly improved achievement of the guideline-recommended LDL-C target after ACS. These findings support a structured, algorithm-based care pathway to facilitate timely initiation and intensification of LLT and improve implementation of guideline-recommended lipid management in routine clinical practice. (Brief and Protocol-Based Intensive Lipid Management in Patients with Acute Coronary Syndrome; jRCT1020240029).
Among the most commonly cited reasons for failure to initiate comprehensive medical therapy in patients with heart failure are concerns relating to hypotension, kidney dysfunction and hyperkalemia. Here we performed a pooled individual participant-level analysis and developed a prediction model to estimate the short-term (2-12 weeks) treatment effects of combination medical therapy on systolic blood pressure (SBP), diastolic BP, estimated glomerular filtration rate (eGFR) and serum potassium. A total of 38,753 participants (16,877 with heart failure with reduced ejection fraction (HFrEF) and 21,876 with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF)) across nine randomized trials were included in the analysis, which tested angiotensin receptor blocker-neprilysin inhibitor (ARNI), steroidal mineralocorticoid receptor antagonist (sMRA), nonsteroidal MRA (nsMRA) and sodium glucose cotransporter-2 inhibitors (SGLT2i). For HFrEF, the estimated mean (95% prediction intervals (PIs)) treatment effect on SBP with combination ARNI + SGLT2i + sMRA therapy was -9.2 (-10.6 to -7.8) mmHg. For HFmrEF/HFpEF, the estimated mean (95% PI) treatment effects on SBP with SGLT2i + sMRA therapy and with SGLT2i + nsMRA therapy were -5.9 (-7.3, -4.6) and -4.8 (-5.7, -4.0) mmHg, respectively. For HFrEF, the estimated treatment effects of ARNI + SGLT2i + sMRA on eGFR and serum potassium were -6.8 (-7.9, -5.4) ml min mand +0.30 (0.25, 0.35) mmol l, respectively. For HFmrEF/HFpEF, the treatment effects for combination SGLT2i + sMRA and SGLT2i + nsMRA on eGFR were -7.7 (-8.9, -6.4) and -6.1 (-6.7, -5.5) ml min m, respectively and for serum potassium were +0.34 (0.29, 0.38) and +0.21 (0.18, 0.25) mmol l, respectively. These analyses provide individualized estimates of the expected treatment effect for any combination of medical therapies in HFrEF and HFmrEF/HFpEF on BP, kidney function and serum potassium.
IMPORTANCE: Diagnosing cardiac amyloidosis remains challenging because current imaging approaches are limited to transthyretin amyloidosis. A noninvasive test capable of directly imaging cardiac amyloidosis from various amyloid types and in multiple organs could address an important unmet diagnostic need.
OBJECTIVE: To evaluate the sensitivity and specificity of 124I-evuzamitide positron emission tomography (PET)/computed tomography (CT) for diagnosing cardiac amyloidosis.
DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter (18 US centers), single-group study evaluating the efficacy of 124I-evuzamitide to diagnose cardiac amyloidosis. This study was conducted from January 14, 2025, to March 12, 2026, including a 60-day follow-up period. Three physicians with cardiac PET/CT experience independently reviewed PET/CT images for visual cardiac 124I-evuzamitide uptake while blinded to clinical data. Three expert clinical amyloidosis physicians, blinded to PET/CT data, independently adjudicated the diagnosis based on the standard-of-care diagnostic algorithm. A total of 195 adults suspected of having cardiac amyloidosis were enrolled when they presented for diagnostic evaluation at participating institutions, excluding patients with an established diagnosis of cardiac or systemic amyloidosis.
INTERVENTIONS: PET/CT scans were obtained 3 to 5 hours after intravenous administration of 1 mCi of 124I-evuzamitide. Potassium iodide (130 mg) was given orally for 3 days starting at least 30 minutes prior to 124I-evuzamitide injection.
MAIN OUTCOMES AND MEASURES: Coprimary end points of this study were to assess the sensitivity and specificity of 124I-evuzamitide for the diagnosis of cardiac amyloidosis.
RESULTS: Overall, 170 patients were included (median [IQR] age, 72 [64-79] years; 75.3% male, 19.2% Black, 79.0% White). Median N-terminal pro-brain natriuretic peptide was 471 pg/mL and 61.7% had New York Heart Association class II or III heart failure symptoms. The overall sensitivity was 94% (95% CI, 85%-98%; P < .001); specificity, 86% (95% CI, 77%-92%; P < .001); positive predictive value, 85% (95% CI, 75%-92%); and negative predictive value, 94% (95% CI, 87%-98%).
CONCLUSIONS AND RELEVANCE: 124I-evuzamitide PET/CT is highly sensitive and specific for diagnosing cardiac amyloidosis with an acceptable safety profile. These results support 124I-evuzamitide PET/CT as a diagnostic test to evaluate patients with suspected cardiac amyloidosis.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06788535.
IMPORTANCE: Transcatheter aortic valve implant (TAVI) is increasingly being performed in younger and healthier patients with severe aortic valve stenosis. Antithrombotic therapy after TAVI is a key element of optimizing valve durability and clinical outcomes.
OBJECTIVE: To evaluate the safety and efficacy of a factor Xa inhibitor non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy strategy vs an acetylsalicylic acid (ASA) monotherapy strategy after TAVI.
DESIGN, SETTING, AND PARTICIPANTS: Between December 2021 and June 2025, 360 participants between the ages of 65 and 80 years undergoing TAVI for severe aortic valve stenosis were enrolled in this prospective, randomized, open-label, blinded end point trial conducted at 3 Norwegian centers managing the majority of TAVI procedures nationally. The last patient completed follow-up on May 19, 2026.
INTERVENTION: A total of 360 participants were randomly assigned (1:1) to receive 12 months of monotherapy with either NOAC (intervention) or ASA (control).
MAIN OUTCOMES AND MEASURES: A predefined co-primary end point strategy was chosen to address both efficacy and safety. The primary efficacy end point was TAVI valve leaflet thrombosis defined as the presence of hypoattenuated leaflet thickening (HALT) on blinded core laboratory 4-dimensional cardiac computed tomographic (CT) scan at 12 months. The primary safety end point was a composite of adjudicated Valve Academic Research Consortium 3 (VARC-3) bleeding events, thromboembolic events, and all-cause death at 12 months.
RESULTS: Of the 360 participants randomized (mean age, 74.5 years [SD, 3.7]; 134 females [37%]), 336 completed the trial (168 in each group). The primary efficacy end point occurred in 27 participants (16.2%) allocated to the NOAC group and in 48 participants (28.6%) allocated to the ASA group (risk ratio, 0.55; 95% CI, 0.37 to 0.82, P = .004). The primary safety end point occurred in 13 participants (7.5%) in the NOAC group and in 19 participants (10.6%) in the ASA group (risk difference, -3.3%; 95% CI, -9.5% to 2.8%; P for noninferiority <.001).
CONCLUSIONS AND RELEVANCE: A strategy of NOAC monotherapy after TAVI reduced the incidence of HALT and was noninferior for bleeding, thromboembolic events, or death compared with acetylsalicylic acid monotherapy. These findings suggest that anticoagulation therapy can be beneficial after TAVI in selected patients.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05035277.
BACKGROUND: Vutrisiran, an RNA interference therapeutic that suppresses hepatic transthyretin production, improved survival and cardiovascular outcomes in transthyretin amyloidosis with cardiomyopathy (ATTR-CM) in HELIOS-B (A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy). Tafamidis, a transthyretin stabilizer, also improves clinical outcomes. Although combining these therapies is mechanistically appealing, clinical evidence supporting this approach is limited.
OBJECTIVES: We sought to evaluate whether the treatment effects of vutrisiran differed according to baseline tafamidis use in HELIOS-B.
METHODS: In HELIOS-B, patients with ATTR-CM were randomized to vutrisiran 25 mg or placebo every 3 months for up to 36 months, with tafamidis use permitted and stratified. We assessed treatment effects according to baseline tafamidis use for the primary outcome of all-cause mortality and recurrent cardiovascular events and secondary endpoints, including individual components of the primary outcome, composite of all-cause mortality, cardiovascular events and outpatient worsening heart failure events, functional capacity (6-minute walk distance), and health status (Kansas City Cardiomyopathy Questionnaire-overall summary score [KCCQ-OSS]).
RESULTS: Among 654 participants, 259 (40%) were receiving tafamidis at baseline. Patients on tafamidis were slightly younger and had higher baseline 6-minute walk distance and higher KCCQ-OSS, while baseline characteristics were generally balanced between randomized groups. The treatment effect estimates of vutrisiran compared with placebo for the primary outcome were directionally consistent across baseline tafamidis strata (rate ratio: 0.79 [95% CI: 0.51-1.21] with tafamidis vs 0.67 [95% CI: 0.49-0.93] without), with no statistically significant interaction (P= 0.55). Similar patterns were observed for all-cause mortality, cardiovascular events, and outpatient worsening heart failure (all P> 0.20), although the magnitudes of the estimated effects were numerically smaller among patients receiving tafamidis at baseline. Vutrisiran preserved 6-minute walk distance in both baseline tafamidis strata (P= 0.24), whereas improvement in KCCQ-OSS appeared attenuated among patients receiving tafamidis at baseline.
CONCLUSIONS: Treatment effect estimates for vutrisiran on clinical outcomes were consistent across baseline tafamidis strata, with no statistically significant interaction according to baseline tafamidis use, with reduced effect size noted in those receiving baseline stabilizers in comparison to monotherapy. These data underscore the need for future prospective studies examining combination therapy in this population. (HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy; NCT04153149).
IMPORTANCE: Pulmonary vein isolation remains the foundational ablation approach for atrial fibrillation (AF), yet outcomes in persistent AF remain suboptimal. Targeting low-voltage zones identified by electroanatomical mapping offers a promising strategy for enhancing ablation success.
OBJECTIVE: To determine whether adjunctive individualized low-voltage zone ablation improves arrhythmia outcomes and health-related quality of life beyond pulmonary vein isolation alone in patients with persistent AF and significant low-voltage zones.
DESIGN, SETTING, AND PARTICIPANTS: Multicenter randomized clinical trial with 12 months of follow-up conducted at 5 Swedish ablation centers between May 18, 2020, and April 9, 2026. Of 936 adult patients undergoing first-time ablation and voltage mapping for persistent AF, 209 with low-voltage zones of 3.0 cm2 or greater were randomized.
INTERVENTIONS: Following pulmonary vein isolation, patients with significant low-voltage zones were randomized to either receive individualized adjunctive low-voltage zone ablation (n = 102) or receive no further ablation (n = 107).
MAIN OUTCOMES AND MEASURES: The primary outcome was freedom from documented atrial arrhythmia without antiarrhythmic drugs at 12 months after 1 or 2 ablation procedures within 6 months. Secondary outcomes were time to first recurrence after a single procedure without antiarrhythmic drugs, health-related quality of life, and safety.
RESULTS: Among the 209 randomized patients (median age, 72 years; 109 females [52.2%]), the primary outcome was achieved more frequently in the pulmonary vein isolation plus low-voltage zone ablation group than in the pulmonary vein isolation alone group. Arrhythmia-free survival was achieved in 69 patients (67.6%) vs 40 patients (37.4%), respectively (unadjusted difference, 30.3% [95% CI, 17.4%-43.2%]; odds ratio, 3.5 [95% CI, 2.0-6.2]; P < .001). Time to first recurrence after a single ablation procedure without antiarrhythmic drugs also favored low-voltage zone ablation (hazard ratio, 0.4; 95% CI, 0.3-0.6; P < .001). Improvements in health-related quality of life were greater in the low-voltage zone ablation group, whereas rates of serious adverse events were similar between groups.
CONCLUSIONS AND RELEVANCE: Adjunctive low-voltage zone ablation added to pulmonary vein isolation improved rhythm outcomes and health-related quality of life without increasing serious adverse events in patients with persistent AF and significant low-voltage zones. These findings support a low-voltage zone-guided ablation strategy in this population.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04377594.
BACKGROUND: Pulmonary hypertension that is caused by left heart disease and is associated with heart failure may be driven by sympathetic overactivation leading to increased pulmonary vascular resistance, right ventricular dysfunction, and poor outcomes. Pulmonary-artery denervation may reduce sympathetic activity, although its clinical effects on left heart disease-associated pulmonary hypertension are unknown.
METHODS: We conducted a multicenter, randomized trial in China involving patients with pulmonary hypertension associated with left heart disease and heart failure. Patients were randomly assigned in a 1:1 ratio to receive pulmonary-artery denervation plus guideline-directed medical therapy or to receive medical therapy alone. The primary outcome was clinical worsening - a composite of death, heart or lung transplantation, hospitalization for heart failure, outpatient worsening of heart failure, or a decline in the 6-minute walk distance - through the latest follow-up.
RESULTS: A total of 264 patients underwent randomization: 134 to receive pulmonary-artery denervation plus medical therapy and 130 to receive medical therapy alone. During a median follow-up of 338 days, the Kaplan-Meier estimated 2-year incidence of clinical worsening was 25.7% in the pulmonary-artery denervation group and 51.5% in the medical-therapy group (hazard ratio, 0.49; 95% confidence interval, 0.30 to 0.82; P = 0.006). Access-site hematomas occurred in two patients in the pulmonary-artery denervation group and in one patient in the medical-therapy group; there were no other procedural complications. Adverse events during follow-up occurred with similar frequency in the two groups.
CONCLUSIONS: Among patients with pulmonary hypertension associated with left heart disease and heart failure receiving guideline-directed medical therapy, pulmonary-artery denervation resulted in fewer events of clinical worsening than medical therapy. (Funded by Pulnovo Medical and others; PADN-HF-PH ClinicalTrials.gov number, NCT05824923.).
BACKGROUND: Following transcatheter aortic valve replacement (TAVR), subclinical leaflet thrombosis-visualized on cardiac computed tomography (CT) as hypoattenuated leaflet thickening (HALT)-is common and might be associated with thromboembolic events.
OBJECTIVES: The NOTION-4 trial investigates different antithrombotic treatment strategies for the prevention of HALT.
METHODS: NOTION-4 was a randomized controlled trial enrolling patients without an indication for oral anticoagulation shortly after successful TAVR. Patients were randomized to lifelong single antiplatelet therapy (SAPT) or 3 months of direct oral anticoagulant (DOAC) therapy followed by lifelong SAPT (DOAC-3m). The primary endpoint was HALT prevalence at 12 months. The trial was powered for superiority of the experimental strategy.
RESULTS: Of 352 patients randomized 1:1, 5 were screen failures or withdrew consent, leaving 176 in the SAPT group and 171 in the DOAC-3m group. At 3 months, HALT was observed in 31.8% of patients receiving SAPT compared with 12.1% of those receiving DOAC-3m. At 1 year, HALT occurred in 32.2% of SAPT patients and 28.3% of DOAC-3m patients with available CT scans (risk difference: -3.9%; 95% CI: -14.4% to 6.6%; P = 0.54). The combined risk of all-cause mortality, stroke, or major/life-threatening bleeding at 12 months was 2.3% in the SAPT group vs 8.2% in the DOAC-3m group (risk difference: 5.9%; 95% CI: 1.2% to 10.6%).
CONCLUSIONS: Among TAVR patients without an indication for oral anticoagulation, 3 months of DOAC therapy significantly reduced the prevalence of HALT at 3 months compared with SAPT; however, this effect was attenuated by 9 months after discontinuation of DOAC therapy. (The Nordic Aortic Valve Intervention Trial 4 [NOTION-4]; NCT06449469).
BACKGROUND: Approximately one half of patients undergoing transcatheter aortic-valve implantation (TAVI) have concomitant coronary artery disease. Although percutaneous coronary intervention (PCI) is often performed before TAVI, the preferred treatment strategy has not been established.
METHODS: We conducted an international, open-label, randomized, noninferiority trial at 48 centers in Europe. Patients with severe aortic stenosis and coronary artery disease were randomly assigned in a 1:1 ratio to a strategy of either TAVI before PCI (TAVI-first group) or PCI before TAVI (PCI-first group). The primary end point was a composite of death from any cause; nonfatal myocardial infarction; ischemia-driven revascularization; rehospitalization related to the valve, procedure, or heart failure; or life-threatening, disabling, or major bleeding at 1 year after randomization. The noninferiority margin was 6.6 percentage points, with testing for noninferiority of TAVI first as compared with PCI first.
RESULTS: A total of 986 patients underwent randomization: 498 were assigned to the TAVI-first group and 488 to the PCI-first group. A primary end-point event occurred in 105 patients (22.2%) in the TAVI-first group and in 112 patients (24.2%) in the PCI-first group (risk difference, -2.0 percentage points; 95% confidence interval, -7.4 to 3.4; P<0.001 for noninferiority). Serious adverse events occurred in 264 patients in the TAVI-first group and in 273 patients in the PCI-first group.
CONCLUSIONS: Among patients with severe aortic stenosis and coronary artery disease, a strategy of TAVI before PCI was noninferior to a strategy of PCI before TAVI with respect to the primary end point at 1 year. (Funded by University Hospital Zurich and others; TAVI PCI ClinicalTrials.gov number, NCT04310046.).
BACKGROUND: The effect of transcatheter tricuspid-valve repair on clinical outcomes, including death and hospitalization for heart failure, in patients with severe tricuspid regurgitation remains uncertain.
METHODS: We randomly assigned patients with symptomatic severe tricuspid regurgitation and an increased risk of future heart-failure events in a 2:1 ratio to tricuspid-valve repair plus medical therapy (tricuspid-repair group) or medical therapy alone (medical-therapy group). The first primary end point was a hierarchical composite of death from any cause, hospitalization for heart failure, and quality-of-life improvement at 1 year, assessed by win ratio. If the between-group difference was significant, a second primary end point would be tested: a composite of death from any cause or hospitalization for heart failure through 3 years.
RESULTS: A total of 360 patients underwent randomization (237 patients were assigned to the tricuspid-repair group and 123 to the medical-therapy group). The mean (±SD) age of the patients was 80.3±6.4 years, and 56.4% were women. The win ratio for the first primary end point was 2.42 (95% confidence interval [CI], 1.76 to 3.33; P<0.001), favoring tricuspid-valve repair. The Kaplan-Meier estimate for freedom from death from any cause or hospitalization for heart failure (second primary end point) through 3 years was 52.4% (95% CI, 43.2 to 63.6) in the tricuspid-repair group and 21.0% (95% CI, 12.7 to 34.6) in the medical-therapy group (hazard ratio for death from any cause or hospitalization for heart failure, 0.40; 95% CI, 0.29 to 0.55; P<0.001). Major adverse events within 30 days occurred in 14 patients (5.9%) in the tricuspid-repair group.
CONCLUSIONS: Among patients with symptomatic severe tricuspid regurgitation, transcatheter tricuspid-valve repair plus medical therapy was superior to medical therapy alone with respect to a hierarchical composite of death from any cause, hospitalization for heart failure, and quality-of-life improvement at 1 year and was also associated with a lower risk of a composite of death from any cause or hospitalization for heart failure through 3 years. (Funded by the German Center for Cardiovascular Research and others; TRIC-I-HF ClinicalTrials.gov number, NCT04634266.).
BACKGROUND: The safety of omitting up-front treatment with aspirin during primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) remains unclear.
METHODS: We conducted a multicenter, open-label, randomized trial in Japan involving patients with STEMI who were undergoing primary PCI. Patients were randomly assigned in a 1:1 ratio before PCI to receive low-dose prasugrel monotherapy or dual antiplatelet therapy (DAPT) with aspirin and low-dose prasugrel for 12 months. The primary outcome was a composite of death from any cause, stroke, or myocardial infarction at 12 months, which was assessed for noninferiority with a prespecified noninferiority margin of 1.50 for the 95% confidence interval of the hazard ratio. The major secondary outcome was major bleeding (defined as a bleeding event of Bleeding Academic Research Consortium [BARC] type 3 [nonfatal major bleeding] or 5 [fatal bleeding]) at 12 months, which was assessed for superiority if noninferiority was established for the primary outcome.
RESULTS: A total of 2216 patients were included in the full analysis population; 1109 were assigned to receive monotherapy and 1107 to receive DAPT. At 12 months, death from any cause, stroke, or myocardial infarction had occurred in 124 patients (Kaplan-Meier estimate, 11.0%) in the monotherapy group and in 94 patients (Kaplan-Meier estimate, 8.5%) in the DAPT group (hazard ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.75; P = 0.40 for noninferiority). Major bleeding had occurred in 61 patients (Kaplan-Meier estimate, 5.6%) in the monotherapy group and in 92 patients (Kaplan-Meier estimate, 8.4%) in the DAPT group (hazard ratio, 0.66; 95% CI, 0.47 to 0.91). The percentages of patients with definite or probable stent thrombosis and serious adverse events appeared to be similar in the two groups.
CONCLUSIONS: Among patients with STEMI who were undergoing primary PCI, low-dose prasugrel monotherapy initiated before PCI was not noninferior to DAPT for 12 months with respect to a composite of death from any cause, stroke, or myocardial infarction at 12 months. (Funded by Boston Scientific Japan; PREMIUM ClinicalTrials.gov number, NCT05709626.).
BACKGROUND: The effectiveness and safety of statins for the primary prevention of cardiovascular events and the extension of disability-free survival among older adults remain uncertain.
METHODS: We conducted a double-blind, randomized, placebo-controlled trial at general medical practices across Australia. Community-dwelling adults at least 70 years of age with no history of cardiovascular disease, diabetes, or dementia were randomly assigned in a 1:1 ratio to receive atorvastatin at a dose of 40 mg once daily or identical placebo. The two primary end points were a composite of death from cardiovascular causes, nonfatal myocardial infarction or stroke, or coronary revascularization (to assess effects on major cardiovascular events) and a composite of death from any cause, dementia, or persistent physical disability (to assess effects on disability-free survival). Analyses were performed according to a hierarchical testing plan.
RESULTS: A total of 9971 participants were enrolled: 4984 were assigned to receive atorvastatin and 4987 to receive placebo. The mean (±SD) age of the participants was 74.7±4.5 years, and 51.9% were women. After a median of 5.9 years, a primary cardiovascular event had occurred in 297 participants (10.9 events per 1000 person-years) in the atorvastatin group and in 412 participants (15.5 events per 1000 person-years) in the placebo group (hazard ratio, 0.70; 95% confidence interval [CI], 0.61 to 0.82; P<0.001). Death from any cause, dementia, or persistent physical disability occurred in 637 participants (21.6 events per 1000 person-years) in the atorvastatin group and in 676 participants (23.0 events per 1000 person-years) in the placebo group (hazard ratio, 0.94; 95% CI, 0.84 to 1.05; P = 0.25). Serious adverse events occurred in 131 participants (2.7%) in the atorvastatin group and in 129 (2.7%) in the placebo group, with musculoskeletal, hepatobiliary, and diabetes-related adverse events occurring more commonly in the atorvastatin group.
CONCLUSIONS: Treatment with atorvastatin led to a lower risk of major cardiovascular events than placebo at a median of 5.9 years but did not result in longer disability-free survival among community-dwelling older adults without clinical cardiovascular disease. (Funded by the National Health and Medical Research Council and others; STAREE ClinicalTrials.gov number, NCT02099123.).
BACKGROUND: The effect of clopidogrel monotherapy as compared with extended dual antiplatelet therapy (DAPT) with clopidogrel and aspirin beyond 12 months after implantation of a drug-eluting stent remains uncertain in patients at high risk for recurrent ischemic events.
METHODS: In this open-label noninferiority trial conducted in South Korea, we enrolled patients with high-risk clinical or lesion characteristics in whom a drug-eluting stent had been implanted 12 months earlier and randomly assigned them, in a 1:1 ratio, to receive clopidogrel monotherapy or extended DAPT (clopidogrel plus aspirin). The primary end point was net adverse clinical events, a composite of death from any cause, myocardial infarction, stent thrombosis, stroke, or Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding at 24 months (noninferiority margin, 2.3 percentage points). Key secondary ischemic and bleeding end points were tested in a prespecified hierarchical order.
RESULTS: Of the 3203 patients who underwent randomization, 1601 were assigned to receive clopidogrel monotherapy and 1602 to receive extended DAPT. Over the course of 24 months, a primary end-point event occurred in 80 patients (5.0%) in the monotherapy group and in 81 (5.1%) in the DAPT group (risk difference, -0.1 percentage points; 90% confidence interval [CI], -1.3 to 1.2; P = 0.001 for noninferiority). Death from any cause, myocardial infarction, stent thrombosis, or stroke (the key secondary ischemic end point) occurred in 60 patients (3.7%) in the monotherapy group and in 26 (1.6%) in the DAPT group (hazard ratio, 2.33; 95% CI, 1.47 to 3.69; P<0.001). BARC type 2, 3, or 5 bleeding (the key secondary bleeding end point) occurred in 28 patients (1.8%) in the monotherapy group and in 65 (4.1%) in the DAPT group (hazard ratio, 0.43; 95% CI, 0.27 to 0.67; P<0.001). The incidence of serious adverse events was similar in the two groups.
CONCLUSIONS: Among patients at high risk for ischemic events 12 months after drug-eluting stent implantation, clopidogrel monotherapy was noninferior to extended DAPT with respect to net adverse clinical events at 24 months. (Funded by Chong Kun Dang and Samjin; A-CLOSE ClinicalTrials.gov number, NCT03947229.).
BACKGROUND: Complete coronary-artery revascularization is recommended in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease, but the preferred strategy for identifying nonculprit lesions that warrant treatment remains uncertain.
METHODS: In this international, randomized trial, we assigned patients with STEMI and multivessel disease in whom the culprit lesion had been successfully treated to undergo complete coronary-artery revascularization guided by functional coronary angiography (physiology-guided group) or by conventional angiography (angiography-guided group). The primary outcome was a composite of death from any cause, myocardial infarction, cerebrovascular accident (stroke or transient ischemic attack), or ischemia-driven revascularization, assessed in a time-to-event analysis. The primary safety outcome was a composite of contrast-associated acute kidney injury or major bleeding.
RESULTS: A total of 1823 patients underwent randomization; 913 were assigned to the physiology-guided group and 910 assigned to the angiography-guided group. The median age of the patients was 66 years (interquartile range, 58 to 76), and 24% were women. At a median follow-up of 17.9 months, a primary-outcome event had occurred in 81 patients (8.9%) in the physiology-guided group and in 125 patients (13.7%) in the angiography-guided group (hazard ratio, 0.62; 95% confidence interval [CI], 0.47 to 0.83; P<0.001). A primary-safety-outcome event occurred in 42 patients (4.6%) in the physiology-guided group and in 65 patients (7.1%) in the angiography-guided group (hazard ratio, 0.63; 95% CI, 0.43 to 0.93; P = 0.02).
CONCLUSIONS: In patients with STEMI and multivessel coronary artery disease, a strategy of complete coronary-artery revascularization guided by functional coronary angiography resulted in a lower risk of a primary-outcome event (death, myocardial infarction, cerebrovascular accident, or ischemia-driven revascularization) than a strategy guided by conventional angiography. (Funded by the Italian Health Ministry and others; AIR-STEMI ClinicalTrials.gov number, NCT05818475.).
The selection of the optimal antithrombotic regimen in patients with atrial fibrillation and acute coronary syndrome remains challenging. Previous trials have demonstrated that dual antithrombotic therapy (DAT), consisting of direct oral anticoagulants (DOACs) plus a P2Y12 inhibitor, reduces bleeding compared to a triple-therapy regimen using vitamin K antagonists. However, subsequent meta-analyses have suggested an increased risk of ischemic events with DAT, particularly within the first month of treatment. Clopidogrel has been the predominant P2Y12 inhibitor used across these studies, despite the risk of high on-treatment platelet reactivity when using this drug. In this study, we conducted an open-label, randomized controlled trial (EPIDAURUS) in patients with atrial fibrillation and acute coronary syndrome, designed to assess the efficacy and safety of a 1-month regimen of DOAC plus potent P2Y12 inhibitor (prasugrel or ticagrelor) compared to DOAC plus clopidogrel and in-hospital aspirin. The primary outcomes of the trial were an efficacy endpoint, recurrent ischemic events and safety endpoints, including death and major bleeding, which were evaluated 6 weeks after randomization using separate win-loss ratio analyses. The study was prematurely terminated after enrollment of 602 patients (154 female) of an expected 1,474 patients, owing to safety concerns raised by the Data and Safety Monitoring Board. Exploratory analyses of secondary safety endpoints, including bleeding type ≥2 and ≥3 according to the Bleeding Academic Research Consortium scale, revealed that, compared to clopidogrel and in-hospital aspirin, treatment with a potent P2Y12 inhibitor was associated with higher bleeding rates without a clear reduction in the risk of ischemic complications. These findings do not support the routine use of potent P2Y12 inhibitors in combination with DOACs in this patient population. ClinicalTrials.gov identifier: NCT04981041 .
IMPORTANCE: Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibition is recommended as second- or third-line lipid-lowering therapy after myocardial infarction (MI), resulting in prolonged periods of inadequate low-density lipoprotein cholesterol (LDL-C) control. Whether in-catheterization laboratory decision of PCSK9 inhibition, started before mechanical reperfusion, could improve LDL-C control and clinical outcomes at 1 year is unknown.
OBJECTIVE: To evaluate evolocumab as first-line therapy vs standard care in patients with high-risk acute MI undergoing percutaneous coronary intervention (PCI).
DESIGN, SETTING, AND PARTICIPANTS: This international, phase 4, prospective randomized, open, blinded end-point adjudication study was conducted at 48 sites in 6 countries. Adults with high-risk ST-elevation MI (STEMI; aged >55 years) or non-ST-elevation MI (NSTEMI) with 1 or more additional high-risk characteristics were enrolled beginning September 29, 2021, through May 22, 2025, with final follow-up on May 22, 2026.
INTERVENTIONS: Patients were randomized 1:1 to receive evolocumab 140 mg subcutaneously every 2 weeks for 1 year (first injection before PCI) in addition to standard care (n = 1087) or standard care alone (n = 1074). Standard care included high-intensity oral lipid-lowering therapy with the optional PCSK9 inhibitor use per guideline indication in the control group.
MAIN OUTCOMES AND MEASURES: The primary outcome was LDL-C less than 55 mg/dL and at least 50% reduction in LDL-C from baseline at 12 months. The main clinical end point was all-cause death or unplanned cardiovascular hospitalization at 12 months.
RESULTS: Among 2161 randomized patients (mean age, 67 years; 1703 males [79%]; 1261 [58%] with STEMI; 900 [42%] with NSTEMI), the primary outcome was achieved in 792 of 970 patients (82%) with evolocumab vs 370 of 934 (40%) with standard care (adjusted odds ratio, 5.54 [95% CI, 4.50-6.82]; P < .001). At 6 weeks, median LDL-C was 16 mg/dL with evolocumab vs 56 mg/dL with standard care. The main clinical end point occurred in 159 of 1087 patients (14.6%) with evolocumab vs 165 of 1074 (15.4%) with standard care (adjusted odds ratio, 0.94 [95% CI, 0.73-1.19]; P = .59).
CONCLUSIONS AND RELEVANCE: In patients with acute MI undergoing PCI, first-line evolocumab combined with high-intensity lipid-lowering therapy produced rapid and sustained LDL-C reduction, with more than 80% of patients reaching the guideline-recommended target at 1 year. However, no clinical benefit was detected during the first year of follow-up, arguing against clinically meaningful acute pleiotropic effects of PCSK9 inhibitors in addition to standard care.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04951856.
BACKGROUND: Patients are at increased risk for recurrent ischemic events after an acute coronary syndrome event. Milvexian, an oral factor XIa inhibitor, may reduce the risk of major adverse clinical events with minimal bleeding risk.
METHODS: In this phase 3, randomized, placebo-controlled trial, we evaluated the efficacy and safety of milvexian when added to standard antiplatelet therapy within 7 days after an acute coronary syndrome event. Patients were assigned in a 1:1 ratio to receive oral milvexian (25 mg twice daily) or matched placebo. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or ischemic stroke as evaluated in a time-to-event analysis. The principal safety outcome was Bleeding Academic Research Consortium (BARC) type 3c or 5 bleeding (intracranial or intraocular bleeding that compromises vision or fatal bleeding).
RESULTS: After a planned interim analysis that was based on 556 adjudicated efficacy end points, the trial was terminated for futility. A total of 14,194 patients had been enrolled, with 7094 assigned to receive milvexian and 7100 to receive placebo. After a median follow-up of 12.2 months, a primary efficacy outcome event had occurred in 384 patients (5.4%) in the milvexian group and in 365 patients (5.1%) in the placebo group (hazard ratio, 1.05; 95% confidence interval, 0.91 to 1.21; P = 0.50). BARC type 3c or 5 bleeding occurred in 23 patients (0.3%) in the milvexian group and in 22 patients (0.3%) in the placebo group (P = 0.88).
CONCLUSIONS: Among patients with a recent acute coronary syndrome event, milvexian did not decrease the risk of cardiovascular death, myocardial infarction, or ischemic stroke but did not increase the risk of intracranial or fatal bleeding, as compared with placebo. (Funded by Janssen Research and Development and Bristol Myers Squibb; LIBREXIA ACS ClinicalTrials.gov number, NCT05754957.).
BACKGROUND: Whether prasugrel or ticagrelor should be the preferred P2Y12 inhibitor for patients with an acute coronary syndrome is uncertain.
METHODS: We conducted a registry-based, open-label, stepped-wedge, cluster-randomized trial in Sweden involving adults who had undergone percutaneous coronary intervention for an acute coronary syndrome. Seven regions, grouped into three clusters, switched from ticagrelor to prasugrel as the default P2Y12 inhibitor in a randomized sequence across four 9-month periods between 2021 and 2024. The primary end point was a composite of death from any cause, fatal or nonfatal myocardial infarction, or fatal or nonfatal stroke through 1 year, as ascertained from national registries. In the intention-to-treat analysis, a mixed model adjusted for cluster and calendar time was used to obtain a policy-level estimate.
RESULTS: A total of 17,095 patients were enrolled; 9444 received care under the default ticagrelor policy, and 7651 received care under the default prasugrel policy. The mean (±SD) age of the patients was 69.8±11.5 years, and 36.8% were at least 75 years old; 27.8% of the patients were female. A total of 39.4% presented with ST-segment elevation myocardial infarction (STEMI), 43.7% with non-STEMI, and 16.8% with unstable angina. At 1 year, a primary end-point event had occurred in 11.8% of the patients in the ticagrelor-policy group and in 11.1% of those in the prasugrel-policy group (adjusted odds ratio [prasugrel vs. ticagrelor], 0.90; 95% confidence interval [CI], 0.77 to 1.06), and major bleeding had occurred in 4.4% and 4.2%, respectively (adjusted odds ratio, 0.80; 95% CI, 0.64 to 0.99).
CONCLUSIONS: In an unselected population of patients with an acute coronary syndrome who had undergone percutaneous coronary intervention, the risk of ischemic events was not lower with a default prasugrel policy than with a default ticagrelor policy. (Funded by Region Västra Götaland; SWITCH-SWEDEHEART ClinicalTrials.gov number, NCT05183178.).
BACKGROUND: Atherosclerosis may begin in early adulthood and remain clinically silent for decades before cardiovascular disease manifests. Although silent atherosclerosis is associated with cardiovascular events and death independent of traditional cardiovascular disease risk factors, its age- and sex-specific prevalence, vascular territory distribution, and plaque volume across adult life remain incompletely defined.
METHODS: We conducted a prospective cohort study in Denmark and Spain. Adults 18 to 70 years of age without known atherosclerotic cardiovascular disease were enrolled in five prespecified age strata that included balanced numbers of women and men. Silent atherosclerosis was assessed at baseline with three-dimensional vascular ultrasonography of the carotid and femoral arteries and with coronary computed tomographic angiography.
RESULTS: A total of 16,808 adults were enrolled in the study. The mean (±SD) age of the participants was 45±12 years, and 51.4% were women. Silent atherosclerosis was present in 57.1% of the participants (95% confidence interval, 56.3 to 58.0). In the youngest age stratum (18 to 29 years), atherosclerosis was present in 8.7% of the men and 6.7% of the women; prevalence increased with age, with a later, steeper midlife rise among women. Among participants in the younger age strata, atherosclerosis was most often peripheral and confined to a single vascular territory; with increasing age, plaque volume increased exponentially and the prevalence of multiarterial involvement became more frequent. Isolated coronary-artery atherosclerosis was uncommon in every age stratum (≤9.3% of men and ≤5.0% of women).
CONCLUSIONS: This study of silent atherosclerosis showed that the disease was detectable in early adulthood, with age- and sex-associated increases in prevalence across arterial territories and marked increases in plaque volume. (Funded by the Novo Nordisk Foundation; REACT ClinicalTrials.gov number, NCT06692127.).
IMPORTANCE: Pulmonary vein isolation (PVI) is less effective in persistent than in paroxysmal atrial fibrillation (AF).
OBJECTIVE: To determine whether adding posterior left atrial wall isolation (PWI) to pulsed field ablation (PFA)-based PVI reduces atrial tachyarrhythmia in patients with persistent AF.
DESIGN, SETTING, AND PARTICIPANTS: This investigator-initiated, multicenter, randomized superiority trial with blinded end-point adjudication was conducted at 6 centers in Switzerland. Patients with symptomatic, persistent AF were enrolled from November 2023 to February 2025, with 1-year follow-up completed February 2026.
INTERVENTION: Patients were randomized 1:1 to PFA-based PVI with PWI vs PFA-based PVI alone. All patients received an implantable cardiac monitor (ICM) after ablation.
MAIN OUTCOMES AND MEASURES: The primary end point was first recurrence of atrial tachyarrhythmia during days 91 to 365 after ablation, detected by continuous ICM monitoring and adjudicated by an independent clinical events committee blinded to treatment allocation. There were 29 secondary end points, including atrial arrhythmia burden during days 91 to 365, time to arrhythmia recurrence during days 91 to 365 using different minimum episode durations, and a safety composite, which comprised cardiac tamponade requiring drainage, persistent phrenic nerve palsy lasting more than 24 hours, serious vascular complications requiring intervention, stroke or transient ischemic attack, atrioesophageal fistula, or death up to day 90.
RESULTS: Among 206 randomized patients (mean [SD] age, 65.8 [9.2] years; 165 [80.1%] males; 102 randomized to PVI with PWI; 104 randomized to PVI alone), atrial tachyarrhythmia recurred in 51 of 102 patients (50.6%) assigned to PVI with PWI and in 63 of 104 patients (60.6%) assigned to PVI alone (rate ratio [RR], 0.75 [95% CI, 0.51-1.09]; P = .13). Of the 29 prespecified secondary outcomes, 22 were not significantly different. The mean atrial arrhythmia burden was 6.9% and 11.0%, respectively (difference, -4.1 percentage points; 95% CI, -8.0 to -0.2 percentage points; P = .04). Across minimum episode durations of 1 hour or longer, 6 hours or longer, 1 day or longer, 2 days or longer, and 7 days or longer, RRs for PVI with PWI vs PVI alone were 0.64 (95% CI, 0.41-0.99), 0.62 (95% CI, 0.38-1.03), 0.37 (95% CI, 0.18-0.78), 0.40 (95% CI, 0.18-0.88), and 0.51 (95% CI, 0.22-1.23), respectively. The safety composite end point occurred in 2 patients assigned to PVI with PWI.
CONCLUSIONS AND RELEVANCE: In patients with persistent AF, adding PFA-based PWI to PVI did not significantly reduce atrial tachyarrhythmia recurrence lasting 30 seconds or longer compared with PVI alone. The findings for secondary end points are hypothesis generating and warrant further evaluation in a larger trial.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05986526.
BACKGROUND: Patients with myocardial infarction and large thrombus burden face greater infarct size and higher mortality, yet no effective therapy exists for this high-risk subgroup.
OBJECTIVES: To investigate the effects of stent-retriever thrombectomy in addition to conventional percutaneous coronary intervention (PCI) versus conventional PCI alone on infarct size.
METHODS: In this open-label, multicenter, superiority trial, 160 patients with ST-segment elevation myocardial infarction and large thrombus burden at angiography (TIMI thrombus grade ≥3 in infarct-related artery) were consented and 156 randomly assigned to undergo stent-retriever thrombectomy followed by conventional PCI or conventional PCI alone. Primary outcome was infarct size extension assessed by area under the curve (AUC) for creatine kinase (CK)-MB. Safety outcome was major adverse cardiovascular events (MACE; comprising cardiovascular death, nonfatal myocardial infarction, nonfatal stroke), at 3 and 30 days.
RESULTS: Infarct size (CK-MB AUC) was lower in the stent-retriever group (n=78) versus the conventional group (n=76) (3965 IU/L·h; interquartile range [IQR] 2480-5092 versus 5250; IQR 3506-7449; difference -1359, 95% CI -2231 to -522; p=0.001). At exploratory cardiac magnetic resonance findings, infarct size was lower in the stent-retriever group (n=64; left ventricle, 17%; IQR 11-28) versus the conventional PCI group (n=59; 28.0%; IQR 18-33; difference -7.0, 95% CI -12 to -2.0), whereas left ventricular volumes and ejection fraction did not differ. There was no MACE at 3 days and 1 at 30 days in the stent-retriever group versus 2 and 3, respectively, in the conventional PCI group.
CONCLUSIONS: Stent-retriever thrombectomy followed by conventional PCI in patients with large thrombus burden undergoing primary PCI ≤8 hours of symptom onset was associated with reduced infarct size versus conventional PCI alone.
BACKGROUND: Many patients with suspected acute coronary syndrome in whom myocardial infarction has been ruled out in the emergency department remain at risk for cardiovascular events. Whether further investigation reduces this risk is unknown.
METHODS: In a multicenter, randomized, controlled trial, patients who presented to an emergency department in 14 hospitals across the United Kingdom were enrolled if myocardial infarction had been ruled out and high-sensitivity cardiac troponin testing indicated an intermediate risk of a cardiovascular event (maximum high-sensitivity cardiac troponin I or T concentration, >5 ng per liter). Participants were randomly assigned in a 1:1 ratio to receive either outpatient computed tomographic (CT) coronary angiography-guided care or standard care. The primary outcome was a composite of myocardial infarction or death from a cardiac cause.
RESULTS: From September 18, 2019, to May 11, 2023, a total of 3170 participants (median age, 61 years; female sex, 30.2%) were assigned to undergo CT coronary angiography (1587 participants) or receive standard care (1583 participants). At 90 days after randomization, CT coronary angiography had been performed in 1462 participants (92.1%) in the CT coronary angiography group and in 35 participants (2.2%) in the standard-care group. Overall, 7 participants (0.4%) had a CT coronary angiography-related adverse event. After a median of 3.0 years, at which point the number of primary-outcome events in the standard-care group exceeded the prespecified minimum of 97, a primary-outcome event had occurred in 112 participants (7.1%) in the CT coronary angiography group and in 116 (7.3%) in the standard-care group (adjusted hazard ratio, 0.95; 95% confidence interval, 0.73 to 1.23; P = 0.71).
CONCLUSIONS: In patients with suspected acute coronary syndrome in whom myocardial infarction had been ruled out, routine CT coronary angiography-guided management did not result in a lower incidence of subsequent myocardial infarction or death from a cardiac cause than standard care. (Funded by the British Heart Foundation; TARGET-CTCA ClinicalTrials.gov number, NCT03952351.).
BACKGROUND: Computed Tomography-derived Fractional Flow Reserve (FFRct) integrates anatomical and functional information, which is particularly useful for stable coronary artery disease (CAD) patients with at least intermediate stenosis.
OBJECTIVES: We investigated the impact of adding FFRct to the diagnostic pathway of CAD patients with a 50-90% stenosis on Coronary Computed Tomography Angiography (CCTA).
METHODS: FUSION is an investigator-initiated, multicenter, randomized controlled trial involving patients with 50-90% stenosis in ≥1 coronary artery on CCTA. Patients were randomized to FFRct-guided or usual care. The primary endpoint was invasive coronary angiography (ICA) without obstructive CAD at 90 days. Secondary endpoints included ICA without obstructive CAD, major adverse cardiac events (MACE), and costs at 1 year, as well as revascularizations, and quality of life at 90 days and 1 year. ICA use was assessed as a post-hoc exploratory endpoint.
RESULTS: Overall, 528 patients (median age 63 [57-69] years, 59% male) were randomized to FFRct-guided (n=263) or usual care (n=265). At 90 days, the rate of ICA without obstructive CAD was significantly lower in the FFRct group than in the usual care group (18% (48/263) versus 33% (87/265); odds ratio 0.46; 95% confidence interval, 0.31-0.69; P<0.001). ICA rate was 39% (102/263) versus 51% (136/265), respectively (P=0.004). Both differences persisted at 1 year. Revascularization rates were similar: 20% (52/263) versus 20% (53/265) at 1 year, respectively (P=0.948). Quality of life, costs, and MACE did not differ between groups, although the clinical event rates were low.
CONCLUSIONS: Adding FFRct to the diagnostic pathway of patients with a 50-90% stenosis on CCTA reduced the rate of ICA without obstructive CAD at 90 days and 1 year, without differences in revascularizations, quality of life, and costs compared to usual care. Clinical event rates were similar, although low. The rate of overall ICA use, a post-hoc exploratory outcome, was also reduced at 90 days and 1 year.
BACKGROUND: Nonobstructive hypertrophic cardiomyopathy (HCM) is a common condition that is associated with substantial morbidity and no proven medical therapy. Whether treatment with aficamten, a cardiac myosin inhibitor, can benefit patients with this condition is unknown.
METHODS: In this phase 3, multinational, double-blind trial, we randomly assigned adults with symptomatic nonobstructive HCM in a 1:1 ratio to receive aficamten (starting dose, 5 mg; maximum dose, 20 mg) or placebo for up to 72 weeks. The dual primary end points were the change from baseline to week 36 in peak oxygen uptake and in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; range, 0 to 100, with higher scores indicating better health status).
RESULTS: A total of 258 patients were assigned to receive aficamten and 259 to receive placebo. The mean age of the patients was 55.1 years, and 53.6% were women. At 36 weeks, the change in the KCCQ-CSS was 11.4 points (95% confidence interval [CI], 9.6 to 13.2) in the aficamten group and 8.4 points (95% CI, 6.6 to 10.2) in the placebo group (least-squares mean difference, 3.0 points; 95% CI, 0.5 to 5.5; P = 0.02). The mean change in the peak oxygen uptake at week 36 was 0.64 ml per kilogram of body weight per minute (95% CI, 0.32 to 0.95) in the aficamten group and -0.03 ml per kilogram per minute (95% CI, -0.35 to 0.28) in the placebo group (least-squares mean difference, 0.67 ml per kilogram per minute; 95% CI, 0.22 to 1.11; P = 0.003). Reversible reductions in left ventricular ejection fraction to less than 50% occurred in 27 patients (10.5%) receiving aficamten and in 2 patients (0.8%) receiving placebo. Serious adverse events occurred in 52 patients (20.2%) and 38 patients (14.7%), respectively.
CONCLUSIONS: Among patients with symptomatic nonobstructive HCM, treatment with aficamten resulted in a significantly greater change in exercise capacity and patient-reported health status than placebo at 36 weeks. (Funded by Cytokinetics; ACACIA-HCM ClinicalTrials.gov number, NCT06081894.).
BACKGROUND: Current U.S. and European guidelines recommend oral anticoagulation as a class IIa indication in patients with atrial fibrillation at intermediate risk for stroke; however, evidence from randomized trials is needed.
METHODS: We conducted a multicenter, open-label, adjudicator-masked superiority trial in South Korea involving patients with atrial fibrillation and an intermediate risk of stroke (a score of 1 in men and 2 in women on the CHADS-VASc scale; range, 0 to 9, with higher scores indicating a greater risk of stroke). Patients were randomly assigned in a 1:1 ratio to receive either direct oral anticoagulant (DOAC) therapy or no anticoagulation. The primary end point was a composite of stroke, systemic embolism, major bleeding, or death from cardiovascular causes at 24 months.
RESULTS: Of 1803 patients who underwent randomization, 902 were assigned to receive DOAC therapy and 901 were assigned to receive no anticoagulant therapy. The mean age of the patients was 60.4 years, and 23.7% were women. At 24 months, a primary end-point event had occurred in 4 patients (cumulative incidence, 0.5%) in the DOAC group and in 13 (cumulative incidence, 1.5%) in the no-anticoagulant group (difference, -1.0 percentage points; 95% confidence interval [CI], -2.0 to -0.1; P = 0.03; hazard ratio, 0.31; 95% CI, 0.10 to 0.94). Stroke occurred in 3 patients (cumulative incidence, 0.3%) in the DOAC group and in 10 (cumulative incidence, 1.1%) in the no-anticoagulant group. The incidence of systemic embolism and major bleeding appeared to be similar in the two trial groups, and no deaths from cardiovascular causes occurred in either group. Serious adverse events occurred in 80 patients (8.9%) in the DOAC group and in 84 (9.3%) in the no-anticoagulant group.
CONCLUSIONS: Among patients with atrial fibrillation at intermediate risk for stroke, DOAC therapy led to a lower risk of stroke, systemic embolism, major bleeding, or death from cardiovascular causes at 24 months than no anticoagulation. (Funded by the Ministry of Health and Welfare, South Korea, and others; SINGLE-AF ClinicalTrials.gov number, NCT04437654.).
IMPORTANCE: Current guidelines do not recommend primary prevention implantable cardioverter-defibrillators (ICDs) unless a patient's left ventricular ejection fraction (LVEF) is 35% or less. Many sudden cardiac deaths (SCD) occur when LVEF is 36% to 50%. Myocardial scar (a key arrhythmic substrate) can be assessed by late gadolinium enhancement on cardiovascular magnetic resonance (CMR), but robust evidence is lacking regarding a scar-based approach to ICD insertion.
OBJECTIVE: To determine whether implantation of ICDs reduces SCD or hemodynamically significant ventricular arrhythmia (HSVA) in patients with an LVEF of 36% to 50% and myocardial scar.
DESIGN, SETTING, AND PARTICIPANTS: An open-label randomized clinical trial enrolled adults between 2015 and 2022 who had ischemic or nonischemic cardiomyopathy, an LVEF of 36% to 50%, CMR-defined myocardial scar, and were receiving guideline-directed medical therapy at 18 sites in Australia, Germany, and the UK. Follow-up assessments were completed in 2026.
INTERVENTIONS: A primary prevention ICD (n = 180) vs an implantable loop recorder (ILR) (n = 173).
MAIN OUTCOMES AND MEASURES: The primary composite outcome was SCD or HSVA. Five secondary outcomes were evaluated: SCD, HSVA, heart failure-related hospitalization, cardiovascular mortality, and all-cause mortality.
RESULTS: Of 353 patients randomized (median age, 65 years [IQR, 57-61 years]; 18% female; and 72% had an ischemic etiology), 70% had an LVEF of 40% or greater. The median follow-up was 6.3 years (IQR, 4.8-7.6 years). The primary composite outcome occurred in 14 patients (7.8%) in the ICD group compared with 16 patients (9.2%) in the ILR group (hazard ratio [HR], 0.76 [95% CI, 0.37-1.58]). For the individual components of the primary composite outcome, SCD occurred in 3 patients (1.7%) vs 10 patients (5.8%) in the ILR group (HR, 0.26 [95% CI, 0.07-0.95]) and HSVA occurred in 12 patients (6.7%) vs 6 patients (3.5%), respectively (HR, 1.77 [95% CI, 0.65-4.81]). The rates for all-cause mortality, cardiovascular mortality, and heart failure-related hospitalization were similar between groups. In a prespecified analysis of 6 subgroups, the primary outcome occurred less often in patients younger than 70 years in the ICD group (3.3%) vs patients in the ILR group (10.0%) (HR, 0.28 [95% CI, 0.09-0.89]) but not in those aged 70 years or older (16.9% vs 7.5%, respectively) (HR, 2.33 [95% CI, 0.75-7.26]; P = .01 for interaction).
CONCLUSIONS AND RELEVANCE: Implantation of an ICD did not reduce the composite outcome of SCD or HSVA in patients with an LVEF of 36% to 50% and myocardial scar.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01918215.
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab reduced the risk of a first major adverse cardiovascular event (MACE) in patients at high cardiovascular risk with no prior myocardial infarction (MI) or stroke in the VESALIUS-CV (Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke) trial. Recurrent MACE is common and important to patients, clinicians, and health care systems.
OBJECTIVES: The purpose of this study was to evaluate the effect of evolocumab on total (first and subsequent) MACE.
METHODS: The VESALIUS-CV trial randomized patients with qualifying atherosclerosis or high-risk diabetes, no prior MI or stroke, and a low-density lipoprotein cholesterol ≥90 mg/dL on optimized lipid-lowering therapy to evolocumab or placebo. The dual primary endpoints were a composite of coronary heart disease death, MI, ischemic stroke, or ischemia-driven arterial revascularization (4-point [4-P] MACE) and 3-point (3-P) MACE (not including ischemia-driven arterial revascularization). In this prespecified analysis, all dual primary endpoint events (first and subsequent) were analyzed using negative binomial regression models.
RESULTS: Among 12,257 patients followed for a median of 4.6 years, there were 1,654 first 4-P MACE and 1,107 subsequent events (67% more) for 2,761 total events. There were 779 first 3-P MACE and 146 subsequent events (19% more) for 925 total events. Evolocumab reduced the rate of first 4-P MACE by 19% (HR: 0.81; 95% CI: 0.73-0.89; P < 0.0001), was associated with a reduction of subsequent events by 25% (incidence rate ratio [IRR]: 0.75; 95% CI: 0.61-0.91), and reduced total events by 20% (IRR: 0.80; 95% CI: 0.71-0.90; P = 0.0002). Likewise for 3-P MACE, evolocumab reduced the rate of first events by 25% (HR: 0.75; 95% CI: 0.65-0.86; P < 0.0001), was associated with a reduction of subsequent events by 37% (IRR: 0.63; 95% CI: 0.42-0.94) and reduced total events by 27% (IRR: 0.73; 95% CI: 0.63-0.86; P = 0.0001). Based on annualized incidence rate differences over the full follow-up period, evolocumab was projected to prevent 31 first and 24 subsequent 4-P MACE, for 55 total events per 1,000 patients over 5 years (95% CI: for the total-event difference: 36-74). The corresponding estimates for 3-P MACE were 20 first and 5 subsequent events, for 25 total events per 1,000 patients over 5 years (95% CI: for the total event difference: 15-37). Results were consistent across key subgroups, including by statin intensity and presence of qualifying atherosclerosis.
CONCLUSIONS: A substantial proportion of patients experiencing a cardiovascular event had more than 1 event. The addition of evolocumab reduced the total number of MACE, providing support for the role of intensive low-density lipoprotein cholesterol lowering to prevent first and subsequent MACE in patients at high cardiovascular risk and no prior MI or stroke. (Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke [VESALIUS-CV]; NCT03872401).
OBJECTIVE: To examine the effect of the Dietary Approaches to Stop Hypertension for Diabetes (DASH4D) diet (a DASH-style diet tailored for diabetes) on biomarkers of glycemia.
RESEARCH DESIGN AND METHODS: In this controlled feeding trial, adults with type 2 diabetes were fed four diets in a random order: DASH4D diet and comparison diet (representative of a typical American diet), each with higher and lower sodium. Each feeding period lasted 5 weeks. Using a modified intention-to-treat approach, we estimated the effect of the DASH4D (versus comparison) diet on fructosamine, fasting glucose, and HbA1c with linear mixed-effects models.
RESULTS: Among 101 participants (mean age 67 years, 65% female, 87% Black adults), compared with the comparison diet, the DASH4D diet significantly reduced end-of-period fructosamine (adjusted difference: -5.6 μmol/L, P = 0.002), fasting glucose (adjusted difference: -4.5 mg/dL; P = 0.02), and HbA1c (adjusted difference: -0.09 percentage points; P = 0.04).
CONCLUSIONS: Our results support recommending the DASH4D diet for glycemic management in type 2 diabetes.
IMPORTANCE: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a treatable cause of heart failure, but diagnosis is often delayed. Accessible tools to prioritize confirmatory evaluation could reduce missed diagnoses when cardiac imaging is limited.
OBJECTIVE: To develop and validate a locally deployable artificial intelligence (AI)-enabled system that identifies patients for further ATTR-CM evaluation from routine electrocardiography (ECG) images.
DESIGN, SETTING, AND PARTICIPANTS: This diagnostic test study used an AI-ECG model developed within Yale New Haven Health (using ECGs from August 2015-June 2023) and temporally validated (July 2023-July 2025). External validation included 5 multinational cohorts and 3 screening cohorts (older Black and Hispanic adults with heart failure; adults with prior carpal tunnel surgery; 99-3902 individuals per cohort).
EXPOSURE: Use of AI-ECG for detecting ATTR-CM from routine ECG images or raw 12-lead signals.
MAIN OUTCOMES AND MEASURES: Area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and positive and negative predictive values for ATTR-CM confirmed by cardiac amyloid radionuclide imaging (CARI) or biopsy. An exploratory analysis evaluated sequential screening with AI-ECG followed by AI-enabled echocardiography.
RESULTS: Development used 28 174 ECGs from 11 291 patients (293 with ATTR-CM). In internal validation (44 123 patients; mean age, 68.5 years; 49.7% female), AUROC was 0.84 (95% CI, 0.79-0.89), with sensitivity of 0.72 and specificity of 0.86 at the prespecified threshold, and was maintained in a specificity stress test among patients with features that mimic ATTR-CM (left ventricular hypertrophy or severe aortic stenosis without amyloid; AUROC, 0.81 [95% CI, 0.75-0.86]) and those referred for CARI (AUROC, 0.78 [95% CI, 0.73-0.84]). Across 5 external cohorts, AUROCs ranged from 0.78 to 0.89. In 3 screening cohorts, AUROCs were 0.76 (95% CI, 0.68-0.83) in the SCAN-MP study (n = 645) and 0.79 (95% CI, 0.65-0.93) and 0.91 (95% CI, 0.82-0.97) in 2 CACTUS study cohorts (n = 251, n = 121). Sequential AI-ECG and AI-enabled echocardiography increased the positive predictive value from 0.24 to 0.66 and reduced sensitivity from 0.84 to 0.68.
CONCLUSIONS AND RELEVANCE: Locally deployable AI applied to ECG images discriminated ATTR-CM across multinational retrospective and screening cohorts. This approach may provide an accessible first step to prioritize selected patients for echocardiography and confirmatory imaging, although intended use and calibration require prospective evaluation.
BACKGROUND: The World Health Organization (WHO) defines anemia as hemoglobin concentration <12 g/dL in women and <13 g/dL in men. Although widely used clinically, these thresholds were based on distributions in healthy populations rather than on outcomes. Whether these WHO thresholds adequately reflect the relationship between hemoglobin concentration and clinical outcomes in patients with heart failure (HF) is uncertain.
OBJECTIVES: We sought to characterize sex-specific associations between hemoglobin concentration and clinical outcomes and to identify the hemoglobin concentrations associated with the lowest observed risk in patients with HF across the spectrum of left ventricular ejection fraction.
METHODS: Patient-level data were pooled from 6 trials in heart failure with reduced ejection fraction (HFrEF) and 5 trials in heart failure with preserved ejection fraction (HFpEF) or heart failure with mildly reduced ejection fraction (HFmrEF). Associations among baseline hemoglobin and a first HF hospitalization or cardiovascular death, the components of this composite, and all-cause death were examined using Cox proportional hazards models. Sex-specific hemoglobin concentrations associated with the lowest incidence rates were estimated using Poisson regression with restricted cubic splines. Outcomes were also examined by hemoglobin categories defined relative to WHO anemia thresholds.
RESULTS: Overall, 25,003 patients with HFrEF (5,581 women, 19,422 men) and 17,210 with HFpEF/HFmrEF (8,763 women, 8,447 men) were included. In HFrEF, median hemoglobin was 13.0 g/dL (Q1-Q3: 12.1-13.9 g/dL) in women and 14.0 g/dL (Q1-Q3: 12.9-15.1 g/dL) in men; corresponding values in HFpEF/HFmrEF were 13.1 g/dL (Q1-Q3: 12.1-14.0 g/dL) and 14.0 g/dL (Q1-Q3: 12.8-15.0 g/dL), respectively. Across HF phenotypes and outcomes, the lowest risk occurred at hemoglobin concentrations of approximately 14 g/dL in women and 15 g/dL in men, above the WHO anemia thresholds. With hemoglobin ≥2 g/dL above the WHO anemia thresholds as the reference, WHO-defined anemia was associated with the highest adjusted risk. Excess risk was also observed at 0 to <1 g/dL above the thresholds.
CONCLUSIONS: In patients with HF, hemoglobin concentrations associated with the lowest risk of death and HF hospitalization were approximately 14 g/dL in women and 15 g/dL in men. Hemoglobin concentrations above WHO anemia thresholds may still carry prognostic information and, in conjunction with other clinical findings, may prompt consideration of potentially reversible contributors such as iron deficiency. (Candesartan Cilexetil in Heart Failure Assessment of Reduction in Mortality and Morbidity [CHARM-Added], NCT00634309; Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity [CHARM-Alternative], NCT00634400; Candesartan Cilexetil in Heart Failure Assessment of Reduction in Mortality and Morbidity [CHARM-Preserved], NCT00634712; A Comparison Of Outcomes In Patients In New York Heart Association [NYHA] Class II Heart Failure When Treated With Eplerenone Or Placebo In Addition To Standard Heart Failure Medicines [EMPHASIS-HF], NCT00232180; Irbesartan in Heart Failure With Preserved Systolic Function [I-Preserve], NCT00095238; Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT], NCT00094302; This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure [PARADIGM-HF], NCT01035255; Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF], NCT01920711; Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF], NCT03036124; Registrational Study With Omecamtiv Mecarbil [AMG 423] to Treat Chronic Heart Failure With Reduced Ejection Fraction [GALACTIC-HF], NCT02929329; Study to Evaluate the Efficacy [Effect on Disease] and Safety of Finerenone in Participants With Heart Failure and Left Ventricular Ejection Fraction [Proportion of Blood Expelled Per Heart Stroke] Greater or Equal to 40% [FINEARTS-HF], NCT04435626).
BACKGROUND: In patients with infective endocarditis on the left side of the heart, the current recommendation of up to 6 weeks of antibiotic therapy is based largely on expert consensus opinion. Whether a clinical response-tailored antibiotic management strategy can shorten treatment duration without compromising safety is unclear.
METHODS: In this international, open-label, randomized trial, we assigned adults in stable condition with infective endocarditis caused by,, or streptococcus species to receive either response-tailored or standard-duration antibiotic therapy. Before randomization, all the patients received at least the prespecified 2 to 4 weeks of therapy and met criteria for clinical stabilization. After randomization, patients in the tailored-therapy group discontinued antibiotics and those in the standard-therapy group continued standard treatment (total duration, 4 to 6 weeks). The primary efficacy end point was days alive without antibiotic treatment for infective endocarditis or bacteremia within 6 months after randomization (tested for superiority). The primary safety end point was a composite of death from any cause, unplanned cardiac surgery, or symptomatic embolic events within 6 months after randomization (tested for noninferiority; margin, 7.5 percentage points). Relapse of bacteremia or infective endocarditis was a key secondary end point.
RESULTS: A total of 508 patients underwent randomization, with 255 assigned to response-tailored therapy and 253 to standard-duration therapy. The median time alive without antibiotic treatment was 183 days (interquartile range, 181 to 183) with tailored therapy and 169 days (interquartile range, 166 to 171) with standard therapy (Hodges-Lehmann estimated difference, 13 days; 95% confidence interval [CI], 12 to 13; P<0.001 for superiority). A primary safety end-point event occurred in 21 patients (8.2%) with tailored therapy and in 27 patients (10.7%) with standard therapy (absolute between-group difference, -2.4 percentage points; 95% CI, -7.7 to 2.7; P<0.001 for noninferiority), indicating noninferiority. Relapse occurred in 13 patients (5.1%) with tailored therapy and in 4 patients (1.6%) with standard therapy (P = 0.04).
CONCLUSIONS: Among patients with infective endocarditis on the left side of the heart, the use of a response-tailored antibiotic strategy resulted in a longer time alive without antibiotic therapy than standard-duration therapy and met the criterion for noninferiority with respect to safety but was associated with a higher incidence of relapse of bacteremia or infective endocarditis. (Funded by Sygeforsikringen "danmark" and others; POET II ClinicalTrials.gov number, NCT03851575.).
BACKGROUND: Paradoxical low-flow, low-gradient (pLFLG) aortic stenosis (AS) has an adverse prognosis in comparison to other AS subtypes. Transcatheter aortic valve replacement (TAVR) has never been compared with optimal medical therapy (OMT) alone in a dedicated randomized trial in this population.
OBJECTIVES: The trial sought to determine whether TAVR added to OMT reduces all-cause mortality in symptomatic patients with pLFLG AS.
METHODS: In this multicenter, open-label trial, patients with symptomatic pLFLG AS (aortic valve area ≤1.0 cm, mean gradient <40 mm Hg, stroke volume index <35 mL/m, ejection fraction ≥50%) were randomly assigned 2:1 to TAVR plus OMT or OMT alone. The primary endpoint was all-cause death, assessed 2 years after enrollment of the last patient. Enrollment was stopped prematurely for slow recruitment.
RESULTS: Of 783 planned patients, 120 (median age 82 years; 53.3% women) were randomized (80 TAVR, 40 OMT). A total of 19 OMT patients eventually crossed over to TAVR, most for symptom progression. The primary endpoint occurred in 29.0% vs 37.1% (HR: 0.83; 95% CI: 0.41-1.66; P = 0.60), and 5-year mortality was 44.9% vs 56.6% (HR: 0.76; 95% CI: 0.43-1.35; P = 0.35). TAVR was associated with improved symptoms (NYHA functional class I/II at 1 year, 83.0% vs 59.0%) and lower cumulative incidence of first endpoint-related rehospitalizations, and there were no differences in functional capacity or quality of life.
CONCLUSIONS: Although the effect of TAVR on mortality remains unresolved, these findings support an individualized strategy with close surveillance and timely TAVR upon clinical deterioration in selected patients with pLFLG AS. Adequately powered randomized trials are needed to define the effect of early TAVR on prognosis. (accuRate Evaluation of Benefit with Optimal medical treatment with or withOut Transcatheter valve repair of PARADOXical low flow low gradient aortic stenosis [REBOOT-PARADOX Trial]; NCT03863132).
BACKGROUND: Coronary vasospasm is highly prevalent in patients with angina and no obstructive coronary arteries (ANOCA). A central mechanism of vasospasm in these patients arises from endothelial dysfunction and smooth muscle hyper-reactivity that disrupt the nitric oxide-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate pathway governing vasodilation. Vericiguat, an sGC stimulator that enhances sGC sensitivity to nitric oxide, may therefore be a therapeutic option for patients with coronary vasospasm.
OBJECTIVES: To evaluate the effects of vericiguat on angina symptoms, endothelial function, peripheral microvascular vasodilator responses, and safety in ANOCA patients with epicardial and/or microvascular vasospasm.
METHODS: In this double-blind, placebo-controlled, randomized crossover trial, patients were randomized 1:1 to vericiguat followed by placebo, or placebo followed by vericiguat. Each treatment period lasted 10 weeks. The primary functional outcome was the difference in peripheral vasodilator function during acetylcholine iontophoresis using laser speckle contrast imaging; the primary symptom outcome was the difference in daily angina episodes, recorded via the ORBITA-app, between treatments.
RESULTS: Among the 57 patients enrolled in the trial, the median age was 55 years [50, 61], and 44 (77%) were female. Vericiguat did not improve peripheral vasodilator function, assessed by LASCA during acetylcholine iontophoresis, compared with placebo on AUC (intervention effect estimate -1221 APU•s, 95% CI -4237 to 1796, p=0.42). For the primary symptom endpoint, the final-day odds ratio for reduction in angina episodes recorded via the ORBITA-app, the posterior was distributed more towards the direction favoring placebo (OR 0.84, 95% CrI 0.65 to 1.04); however, it did not meet the prespecified efficacy or harm criterion (posterior probability of benefit with vericiguat versus placebo 0.07).; episode counts and angina-free days over 70 days were similar between arms. Vericiguat was generally tolerated, with modest reductions in blood pressure, no clinically relevant laboratory abnormalities, and no treatment-related serious adverse events.
CONCLUSIONS: The Vericiguat in Vasospastic Angina trial did not demonstrate evidence of improved peripheral vasodilator function or anginal symptoms in patients with coronary vasospasm. Vericiguat was nonetheless generally tolerated, with no treatment-related serious adverse events. Larger studies with longer treatment exposure could further evaluate the potential clinical effects of vericiguat in patients with coronary vasospasm.
IMPORTANCE: The 2026 American College of Cardiology/American Heart Association/Multisociety Dyslipidemia Guideline newly recommends selective use of coronary artery calcium (CAC) scoring based on a 10-year risk of 3% to less than 10% estimated with the Predicting Risk of Cardiovascular Disease EVENTS (PREVENT) atherosclerotic cardiovascular disease (ASCVD) equations. However, the utility of CAC scoring alongside the PREVENT equations for ASCVD risk estimation is not known.
OBJECTIVE: To determine the change in predictive utility when adding CAC scores to the PREVENT-ASCVD equations.
DESIGN, SETTING, AND PARTICIPANTS: Longitudinal observational cohort study conducted at 6 sites in the United States and enrolling adult participants aged 45 to 79 years without ASCVD at baseline in the Multi-Ethnic Study of Atherosclerosis.
EXPOSURES: Ten-year ASCVD risk with the PREVENT-ASCVD equations before and after adding CAC scores.
MAIN OUTCOMES: Performance metrics for estimation of risk of fatal and nonfatal ASCVD, assessed using the Harrell C statistic, calibration, and net reclassification improvement (NRI) for newly defined ASCVD risk categories: low (<3%); borderline (3% to <5%); intermediate (5% to <10%); and high (≥10%).
RESULTS: A total of 6098 participants were included. At baseline, participant mean age was 61.4 (SD, 9.6) years, 52% were female, mean estimated 10-year ASCVD risk was 6.4% (SD, 4.8%) with the PREVENT-ASCVD base equations, and 49% had a CAC score greater than 0. During 10 years of follow-up, 366 (6%) experienced an ASCVD event. The Harrell C statistic for the PREVENT-ASCVD base equations was 0.73 (95% CI, 0.70-0.75). After adding CAC to the PREVENT-ASCVD base equations, the change in Harrell C statistic was 0.02 (95% CI, 0.01-0.03), and the categorical NRI was 0.095 (95% CI, 0.053-0.137). The calibration slope for the PREVENT-ASCVD base equations was 1.09 (95% CI, 0.93-1.25), and for the PREVENT-ASCVD base plus CAC equations was 0.92 (95% CI, 0.81-1.03). Among those at borderline risk, incident ASCVD occurred in 1.9% of those with CAC score of 0, 3.9% with CAC greater than 0 and less than 100, 7.4% with CAC 100 or greater and less than 300, and 14.3% with CAC 300 or greater.
CONCLUSIONS AND RELEVANCE: Among US adults aged 45 to 79 years, addition of CAC score to the PREVENT-ASCVD equations across all risk groups overall only modestly improved and, in some groups, did not change model discrimination and reclassification. Reclassification results support selective use of CAC in those with borderline to intermediate risk estimated by the PREVENT-ASCVD equations.
PRISM is a prospective, pilot research study that aims to systematically characterize the usefulness of CardiAQ MCG, a bedside magnetocardiography device, in the evaluation of myocardial ischemia and infarction status.
The primary objective of this study is to evaluate the effect of 24-weeks of once daily treatment with TPIP compared with placebo on exercise capacity in adults with PAH.
This open-label extension study will provide post-trial access to pelacarsen (TQJ230) to participants who have successfully completed the double-blind parent study (CTQJ230A12301).
The purpose of this research, which has been determined as non-significant risk by the central IRB overseeing the study, is to obtain information to help further develop a machine (a medical device) to measure the pressure around the brain from the outside (this pressure is called intracranial pressure or ICP). Monitoring and managing ICP is an important part of care for patients with conditions such as Traumatic Brain Injury (TBI). However, the current way of measuring ICP requires surgery to drill a hole into the skull, and therefore can introduce additional risks such as infections and pain.
Recent research has shown it may be possible to measure ICP without needing surgery. This technology is in development, but large amounts of data is required to build these new devices.
Through collecting a large database of information from patients who have both the routine surgical device and the research device applied to their head, the research team will work to develop and test an effective and potentially safer way of monitoring patient ICP.
Acute kidney injury is a common complication after cardiac surgery with cardiopulmonary bypass and is associated with prolonged intensive care unit stay, increased morbidity, and mortality. Fluid overload and venous congestion are increasingly recognized as important contributors to postoperative organ dysfunction. The VExUS score is a bedside ultrasound tool that assesses systemic venous congestion through evaluation of the inferior vena cava and Doppler flow patterns in the hepatic, portal, and intrarenal veins. Although previous studies have suggested an association between VExUS-assessed venous congestion, AKI, and adverse outcomes, evidence regarding its relationship with advanced hemodynamic parameters remains limited. This prospective observational study will enroll adult patients undergoing cardiac surgery with cardiopulmonary bypass. All patients will undergo postoperative VExUS assessment and will be followed for the development of AKI and other postoperative complications. A predefined subgroup of patients undergoing clinically indicated PiCCO monitoring will additionally be evaluated to determine the association between VExUS score and PiCCO-derived hemodynamic parameters. The findings may support the use of VExUS as a noninvasive bedside tool for assessing venous congestion and identifying patients at increased risk of postoperative organ dysfunction after cardiac surgery.
Acute Kidney Injury After Open Heart Surgery · Venous Congestion After Open Heart Surgery
Background:
Injury or diseases of the heart and lung can sometimes cause scar tissue (fibrosis) to build up in those organs. Current imaging scans can see this scar tissue once it has formed, but researchers want to find a way to detect the fibrosis in its earliest stages, while there might still be time to prevent serious damage. A new tracer (a radioactive substance injected during imaging scans) may be able to help.
Objective:
To test a new tracer (18F-FAPI-74) during imaging scans in people with heart or lung disease.
Eligibility:
People aged 18 years and older with lung or heart disease that may cause scarring in those organs.
Design:
Participants will have 6 clinic visits over 2 years.
Participants will be screened: They will have blood tests and tests of their heart and lung function. Those with heart disease will have a magnetic resonance imaging (MRI) scan of the heart.
The study tracer will be used with positron emission tomography (PET)/computed tomography (CT) scans. The study tracer will be injected into a vein in the arm. Participants will lie on a padded bed that slides through a donut-shaped machine.
Participants will have scans with the study tracer 2 times, 8 to 12 months apart. They will also have standard CT scans and blood tests during these visits. They will also have blood tests at 3 and 6 months between these visits.
Participants will have a follow-up visit after 18 to 24 months. The study scans, MRI and standard CT scans, and lung function tests may be repeated....
Intraoperative hemodynamic instability (IOHI) is a common occurrence during cardiac surgery and is associated with organ hypoperfusion. However, the specific impact of IOHI on composite adverse outcomes remains unclear. This prospective cohort study aims to evaluate the association between intraoperative hemodynamic instability (defined as MAP \< 65 mmHg or vasopressor requirement) and major postoperative complications (Delirium, Acute Kidney Injury, Stroke, or Mortality) in adult patients undergoing elective cardiac surgery with cardiopulmonary bypass.
The aim of this trial is to examine the feasibility, acceptability, and potential efficacy of a 12-month course of pravastatin as an antifibrotic agent for managing dysphagia (swallowing problems) in patients previously treated with radiotherapy for head and neck cancer (HNC). The purpose is to assess whether pravastatin, a medication approved in Australia for cholesterol management, can improve swallowing in people with long-term radiation-associated dysphagia following HNC treatment.
The trial will recruit 48 patients, with an anticipated accrual period of approximately 6 months. Eligible patients will be identified from the Principal Investigator's current study, ERADICATE, or through referral by a radiation oncologist or speech pathologist diagnosing radiation-induced dysphagia.
Participants will receive 40 mg of pravastatin daily for up to 12 months, with swallowing assessments conducted before, during, and after treatment.
Radiation-associated Dysphagia · Head &Amp; Neck Cancer
This is a pragmatic, two-group, cluster randomized trial designed to compare strategies for the Anti Tachycardia Pacing (ATP)-setting in the ventricular tachyarrhythmias (VT) zone when implanting a new implantable cardioverter defibrillator (ICD) in patients with heart disease in hospitals in Denmark.
The strategies are: "Burst" or "Ramp" after 1. ATP (which is always burst) in VT zone. VT zone is defined between 180-249 (up to 269 in special cases) heartbeats per minute.
The ICD will give either:
Burst: The ICD is programmed to give ATP with 4 bursts. Or Ramp: The ICD is programmed to give ATP with 1 burst and 3 ramps.
The participating hospitals will be assigned to one of two intervention strategies for periods of 4-months. The given intervention will follow the patient/ICD throughout the life time of the ICD, but with the possibility to reprogram at any time (intention to treat).
It is calculated that the study needs a total of 398 events (second to fourth ATP), which is estimated to require 3980 implanted ICDs. The participants will be followed until the end of the ICD life, which is estimated to be around 10 years.
Type 1 diabetes (T1D) in children involves autoimmune destruction of pancreatic ß- cells, leading to insulin deficiency. Verapamil is an L-type calcium channel blocker that has been used for decades to treat hypertension and certain cardiac conditions. Recent research has revealed its potential as a ß- cell-protective agent. Hence this study will evaluate the effect of once-daily oral verapamil on pancreatic ß- cell reserve , glycemic metrics and daily insulin requirements in children and adolescents with T1D.
This is a single-center, randomized, double-blind, placebo-controlled, single ascending-dose phase 1 clinical study, aimed at evaluating the safety, tolerability, PK, PD and immunogenicity of single subcutaneous administration of MWX401 Injection in healthy Chinese participants and participants with primary mild hypertension.
The study comprises five dose cohorts with a planned enrollment of 46 subjects. The primary endpoint is the incidence and severity of treatment-emergent adverse events. Secondary endpoints include plasma and urinary PK parameters, changes in serum AGT and RAAS components, changes in blood pressure and hemodynamics, and immunogenicity indicators.
This study will compare two different methods to pace the heart to treat heart failure including:
1. The current standard method of implanting a pacing lead in a vein on the surface of the left lower chamber of the heart (left ventricle) to deliver heart failure therapy. This method is called Cardiac Resynchronization Therapy (CRT).
2. The other method is using a lead implanted in the Left Bundle Branch Area (LBBA) of your heart. This method is called Left Bundle Branch Area Pacing or LBBAP. This lead is approved by the Food and Drug Administration (FDA) to be implanted in this area of the heart, but not to provide heart failure treatment.
