Unsupervised Learning Analysis of Triglycerides, Inflammation, Cholesterol, and the Risks of Incident Cardiovascular Disease and Type 2 Diabetes in the Women's Health Study.

Background: Traditional cardiovascular risk assessment entails investigator-defined exposure levels and individual risk markers in multivariable analysis. We sought to determine whether an alternative unbiased learning analysis might provide further insights into vascular risk.

Methods: We conducted an unsupervised learning (k-means cluster) analysis in the Women's Health Study (N=26 443) using baseline levels of triglycerides, high-sensitivity C-reactive protein, and low-density lipoprotein cholesterol to form novel exposures.

Advanced Glycation End-Product Carboxymethyl-Lysine and Incident Heart Failure and Atrial Fibrillation in Older Adults.

Background: Advanced glycation end-products result from chemical modification of proteins under conditions of hyperglycemia or oxidative stress common with advancing age. Advanced glycation end-product (AGE) formation alters vascular and cardiac structure and function, yet the prospective associations of circulating AGEs with heart failure (HF) and atrial fibrillation (AF) have not been studied.

Methods: We evaluated the associations of serum N-carboxymethyl-lysine (CML), a major AGE in tissue proteins, and incident HF and AF in the CHS (Cardiovascular Health Study), a population-based cohort of older adults.

Ticagrelor Paradox: Systematic Review and Network Meta-Analysis.

Background: Based on the landmark PLATO (Platelet Inhibition and Patient Outcomes) and TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction) trials, current guidelines recommend ticagrelor and prasugrel over clopidogrel for acute coronary syndrome. However, subsequent studies have failed to replicate the reported benefits of ticagrelor, raising concerns about the validity of the PLATO trial's findings.

Methods: Randomized trials published until January 2025 were searched on PubMed and Embase and included if they compared 2 of the 3 standard dual antiplatelet therapies: 12 months aspirin plus clopidogrel, prasugrel, or ticagrelor.

Revisiting the Effect of Udenafil on Exercise Performance in Patients With Fontan Circulation: Results of a Post Hoc Analysis of the FUEL Trial.

Background: In the FUEL (Fontan Udenafil Exercise Longitudinal) trial, a positive treatment effect was identified for outcomes at the ventilatory anaerobic threshold but not for the primary outcome, oxygen consumption (Vo) at peak exercise. This disparate response may be explained by the physiologic challenge of improving peak Vo in participants with near-normal baseline exercise performance.

Methods: Participants were divided into subgroups by baseline predicted peak Vo (<80% versus ≥80%).

Association of Left Atrial Function With Mitral Regurgitation: The Atherosclerosis Risk in Communities Study.

Background: Lower left atrial (LA) function may precede LA enlargement and contribute to mitral regurgitation (MR). We examined the association of LA reservoir strain (a measure of LA function) with MR in the ARIC (Atherosclerosis Risk in Communities) study.

Methods: We analyzed ARIC participants with echocardiograms at Visits 5 (2011-2013) and 7 (2018-2019).

Modification of the Cardiac Renal Angina Index for Predicting Adverse Kidney Events After Pediatric Cardiac Surgery.

Background: Pediatric cardiac surgery-associated acute kidney injury is common and associated with poor outcomes, but early prediction is challenging. The purpose of this study was to determine the performance of a modified cardiac renal angina index (cRAI) in predicting adverse renal events and whether biomarker integration (urine neutrophil gelatinase-associated lipocalin) enhances cRAI performance.

Methods: This was a 2-center prospective observational study in children ages 0 to 18 years admitted to the intensive care unit after cardiac surgery.

Long-Term Adherence to Modifiable Factors and Incident Cardiovascular Disease Among Women With a History of Gestational Diabetes: A Prospective Cohort Study.

Background: Women with prior gestational diabetes are at increased risk of cardiovascular disease (CVD), but whether and to what extent this risk is modifiable is unknown.

Methods: NHSII (Nurses' Health Study II) participants (N=4355), who reported a gestational diabetes diagnosis between 1989 and 2001 and were free of type 2 diabetes, CVD, and cancer at baseline were included. Incident CVD included nonfatal myocardial infarction, fatal coronary heart disease, nonfatal/fatal stroke, angiographically confirmed angina, and coronary revascularizations.

Sleep Duration Irregularity and Risk for Incident Cardiovascular Disease in the UK Biobank.

Background: Emerging evidence supports a link between circadian disruption as measured by higher night-to-night variation in sleep duration and increased risk of cardiovascular disease (CVD). It remains unclear whether this association varies by CVD types or may be modified by average sleep duration and genetic risk for CVD.

Methods: Our prospective analysis included 86 219 UK Biobank participants who were free from CVD when completing 7 days of accelerometer measurement from 2013 to 2015.

Prevalence, Characteristics, and Outcomes of Children With Congenital Heart Disease Undergoing Noncardiac Surgery in the Presence or Absence of COVID-19 Infection During the Pandemic.

Background: Children with congenital heart disease undergoing noncardiac surgery are at increased risk of perioperative complications. The objectives of our study are (1) to describe the prevalence and characteristics of children undergoing noncardiac surgery in the presence or absence of COVID-19 infection and (2) describe the association between preoperative diagnosis of COVID-19 and outcomes.

Methods: We identified all children who underwent surgery between 2017 and 2022 in the American College of Surgeons National Surgical Quality Improvement Program pediatric database.

Cerebrospinal Fluid Aβ Biomarkers Predict Recurrent Hemorrhage and Identify Cerebral Amyloid Angiopathy in Patients With Lobar Hemorrhage.

Background: Recurrent hemorrhage represents a significant risk for patients with lobar hemorrhage and underlying cerebral amyloid angiopathy. However, it remains unknown, whether cerebrospinal fluid biomarkers of β-amyloid (Aβ) retention, predict recurrent hemorrhagic events in these patients.

Methods: In this retrospective study, we evaluated patients with first-ever lobar intracerebral hemorrhage or convexity subarachnoid hemorrhage who underwent cerebrospinal fluid analysis of Aβ, Aβ, and Aβ ratio.

Role of Lipoprotein(a) in Atherosclerotic Cardiovascular Disease in South Asian Individuals.

South Asian individuals (SA), representing approximately one quarter of the global population, experience a disproportionately high burden of cardiovascular disease. Some of this increased susceptibility is accounted for by traditional risk factors such as diabetes, hypertension, carbohydrate-rich diets, and rising rates of obesity and metabolic syndrome. However, other previously underappreciated risk factors may also play a crucial role.

Long-Term Incidence of Dementia Following Transient Ischemic Attack: A Longitudinal Cohort Study.

Background: The association between transient ischemic attack (TIA) and dementia is incompletely characterized. Determining the cognitive sequalae of TIA is important as it can function as an early warning sign or additional risk factor for dementia. We sought to determine the long-term incidence of post-TIA dementia and examined whether TIA prompts changes in vascular risk factors.

Heart Disease Mortality in the United States, 1970 to 2022.

Background: Studying trends in mortality is essential to advance understanding of population health. Further evaluation of long-term heart disease mortality trends and subtypes in the United States is needed to guide public health and clinical interventions.

Methods: This study used the National Vital Statistics System Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research data for adults aged 25 years and older in the United States from 1970 to 2022.

Revisiting Abnormalities of Ventricular Depolarization: Redefining Phenotypes and Associated Outcomes Using Tree-Based Dimensionality Reduction.

Background: Abnormal ventricular depolarization, evident as a broad QRS complex on an ECG, is traditionally categorized into left bundle-branch block (LBBB) and right bundle-branch block or nonspecific intraventricular conduction delay. This categorization, although physiologically accurate, may fail to capture the nuances of diseases subtypes.

Methods: We used unsupervised machine learning to identify and characterize novel broad QRS phenogroups.

Prenatal Per- and Polyfluoroalkyl Substance Exposures and Longitudinal Blood Pressure Measurements in Children Aged 3 to 18 Years: Findings From a Racially and Ethnically Diverse US Birth Cohort.

Background: Prenatal per- and polyfluoroalkyl substance (PFAS) exposures may influence offspring blood pressure (BP), but long-term studies in diverse populations remain limited.

Methods: Participants were from the Boston Birth Cohort. We measured PFAS in maternal plasma collected 24 to 72 hours after delivery and extracted children's BP from medical records.

Race and Ethnicity in Heart Failure Trials: Time to Update Recommended Categories for Global Relevance.

Background: The collection of race and ethnicity data in clinical trials using standardized categories is recommended by the US Food and Drug Administration, although this is primarily for domestic reasons. The applicability and understanding of the categories in multinational trials are uncertain.

Methods: We analyzed patient-level data from 13 major heart failure trials, examining race and ethnicity data recorded by country, as recommended by the Food and Drug Administration: "American Indian or Alaska Native," "Asian," "Black or African American," "Native Hawaiian or Other Pacific Islander," and "White" for race and "Hispanic or Latino" as a minimum for ethnicity (with an expanded list of ethnicities available).

Surgical, Hybrid, or Delayed Surgical Stage 1: Single-Ventricle Palliation Pathway Utilization and Outcome Trends.

Background: Pathways for single-ventricle palliation include traditional neonatal surgical stage 1 palliation (SP), hybrid stage 1 palliation (HP; pulmonary artery flow restriction with ductal stenting), and delayed surgical stage 1 palliation (DSP), preceded by pulmonary artery flow restriction and prostaglandins. Findings from studies aiming to determine the optimal pathway are conflicting. We aimed to describe current pathway utilization and outcomes.

Blood Pressure Responses During Exercise Were Associated With Average Home Blood Pressure and Home Blood Pressure Variability: The Electronic Framingham Heart Study.

Background: Abnormal exercise blood pressure (BP) responses are associated with hypertension and cardiovascular disease, but their relationship with home BP over a mid- to long-term time span is unknown.

Methods: At an FHS (Framingham Heart Study) research examination (2016-2019), participants underwent maximum incremental ramp cycle ergometry cardiopulmonary exercise testing with BP measured every 2 minutes. At the same exam, English-speaking participants enrolled in the electronic FHS with an iPhone were provided with a digital BP cuff to measure home BP weekly for 1 year.

Advances in sulfonyl exchange chemical biology: expanding druggable target space.

Targeted covalent inhibitors possess advantages over reversible binding drugs, that include higher potency, enhanced selectivity and prolonged pharmacodynamic duration. The standard paradigm for covalent inhibitor discovery relies on the use of α,β-unsaturated carbonyl electrophiles to engage the nucleophilic cysteine thiol, but due to its rarity in binding sites, the amino acid is often not available for targeting. 10 years ago we highlighted the emerging potential of sulfonyl fluoride chemical probes that were initially found to serendipitously modify residues beyond cysteine, including tyrosine, lysine, histidine, serine and threonine.

Racial and Ethnic Differences in Sodium Sources and Sodium Reduction Behaviors Among US Adults: NHANES 2017 to 2020 Prepandemic.

Background: Nearly all US adults exceed sodium recommendations, which increases cardiovascular risk. Understanding racial and ethnic differences in sodium sources and behaviors could lead to nuanced public health messaging, dietary interventions, and clinical guidance to achieve population-level sodium reduction more equitably.

Methods And Results: Using National Health and Nutrition Examination Survey (NHANES) 2017 to 2020 prepandemic data, racial and ethnic differences in sodium sources and sodium-related behaviors (eg, salt use at the table and in food preparation, doctor advice to reduce sodium, attempts to reduce sodium, and label reading) were assessed using weighted chi-square.

Association of Lipoprotein(a) With Major Adverse Limb Events and All-Cause Mortality Following Revascularization for Chronic Limb-Threatening Ischemia: A Substudy of the BEST-CLI Trial.

Background: The BEST-CLI (Best Endovascular Versus Best Surgical Therapy in Patients With Critical Limb Ischemia) trial tested the optimal initial revascularization strategy in patients with chronic limb-threatening ischemia. Little is known about the prognostic relevance of Lp(a) (lipoprotein[a]) and its modification by renal function in patients with chronic limb-threatening ischemia. We investigated the relationship between Lp(a) and prespecified cardiovascular outcomes.

Contemporary Safety of Ultrasound Enhancing Agents in a Nationwide Analysis.

Background: Ultrasound enhancing agents (UEAs) are an important diagnostic tool for transthoracic or stress echocardiography (TTE/SE) but recent concerns have been raised about their safety in reports from individual health systems. As such, we aimed to identify if UEAs for TTE/SE are associated with serious adverse events within 2 days of administration.

Methods And Results: All-payor nationwide claims from 11.

Impact of Statin Nonacceptance on Cardiovascular Outcomes in Patients With Diabetes.

Background: Many patients with diabetes do not accept statin therapy despite being at increased risk for cardiovascular events compared with the general population. The effects of delaying statin therapy are not well-understood.

Methods: This is a retrospective cohort study that followed adults with diabetes and no preexisting atherosclerotic cardiovascular disease at the Mass General Brigham integrated health system between 2000 and 2018.

Impact of COVID-19 on Prenatal Diagnosis and Surgical Outcomes of Congenital Heart Disease: Fetal Heart Society and Society of Thoracic Surgeons Collaborative Study.

Background: Fetal echocardiography is the mainstay of prenatal diagnosis of congenital heart disease. The COVID-19 pandemic led to shifts in triage of prenatal services. Our objective was to evaluate the impact of COVID-19 restrictions on prenatal diagnosis, surgical outcomes, and disparities in neonatal critical congenital heart disease (CCHD) management in the United States during the pandemic's first year.