Citations

Abstract Cardiovascular disease is the leading cause of morbidity and mortality globally, imposing a substantial patient burden. Digital biomarkers derived from digital health technologies enable quantifiable, near-continuous, real-world capture of pathophysiological signals and are increasingly used across cardiovascular medicine. Their growth is often supported by big data analytics, artificial intelligence and connected sensors within the Internet of Things. This scientific statement systematically reviews digital biomarkers, their clinical utility across the cardiovascular care continuum, and summarizes major methodological and implementation challenges. We searched PubMed/MEDLINE, Embase and Scopus for phase III–IV cardiovascular trials published between 1 January 2019 and 1 August 2024 that collected digital biomarkers. We identified 541 records and included 32 trials (40 reports) enrolling 32 246 participants (44.71% women; mean age 66.2 ± 11.0 years). Heart failure was the most frequent target condition (16 trials, 50%), followed by cardiac implantable electronic devices trials (12 trials, 38%). Digital biomarkers included cardiac rhythm and heart rate, blood pressure, body weight, impedance-based measures, haemodynamic pressures, and physical activity and sleep patterns captured using diverse sensor technologies. Methodological quality was good (modal quality score 5; range 3–7), although most trials were unblinded. Current studies suggest potential clinical utility in selected cardiovascular conditions. Implementation remains challenging because of measurement variability, privacy and regulatory requirements, affordability and reimbursement barriers and inequities in access. Robust validation and outcome- and cost-effectiveness evidence are still needed. Registration number: CRD42024573879.

Background: Disparities exist in the representation of genders in cardiovascular clinical trials. Atrial fibrillation (AF) is associated with significant morbidity and mortality; however, understanding regarding the representation of women in AF-related clinical trials remains limited. Therefore, this systematic review sought to evaluate the representation of women in AF-related clinical trials. Methods: We conducted a systematic review of clinical trials using the PubMed, Scopus, and EMBASE databases from 1996 to January 1st, 2024, focusing on AF-related lifestyle interventions, pharmacological treatments, catheter ablation, and device therapies for AF. Data extraction and analysis encompassed trial characteristics, participant demographics, and funding sources. The primary outcome was the prevalence of female enrollees, quantified through participation-to-prevalence ratios (PPRs). This was estimated overall and stratified by funding source, intervention type, and enrollment region. Results: Of the 103 clinical trials involving 218,322 participants (39.5% female), the PPR ranged from 0.00 to 1.73, with an average PPR of 1.03. Meanwhile, 43% of the trials exhibited female under-representation (PPR, <0.8). University-funded trials showed higher female enrollment (mean PPR, 0.951) compared to industry/government-funded trials (mean PPR, 0.800). No differences were observed in the representation of women when comparing enrollment regions or intervention types. Conclusions: Despite advancements in AF management, gender disparities persist in AF-related clinical trial representation, particularly in industry/government-funded studies compared to university-funded trials. Thus, addressing implicit biases and enforcing sex equality guidelines are critical steps toward more inclusive cardiovascular research.

Abstract Background Individuals with cancer are at increased risk of acute myocardial infarction (AMI), yet selecting optimal dual antiplatelet therapy (DAPT) remains challenging due to competing risks of thrombosis and bleeding. Aims This study examined patterns of DAPT use and associated outcomes following AMI in patients with active cancer. Methods Using the TriNetX global registry, we identified adults hospitalised with AMI and active cancer between January 2015 and January 2020. Outcomes assessed included all-cause mortality, major bleeding, and AMI readmission up to five years. Results Among 20,000 patients, 78.6% received clopidogrel, 17.6% ticagrelor, and 3.9% prasugrel as their second antiplatelet agent. Those prescribed clopidogrel were older (72.6 ± 10.5 years) than those on ticagrelor (69.8 ± 10.9) or prasugrel (67.2 ± 10.4; p &lt; 0.001) and had a higher prevalence of cardiovascular comorbidities, including hypercholesterolemia (clopidogrel: 62% vs ticagrelor: 53% and prasugrel: 58%) and hypertension (clopidogrel: 77% vs ticagrelor: 69% and prasugrel: 72%). After adjustment for baseline characteristics, five-year mortality was lower with prasugrel and ticagrelor compared with clopidogrel (clopidogrel 29.1%, prasugrel 23.6%, p = 0.03; ticagrelor 30.1%, prasugrel 23.6%, p = 0.01). No significant differences were observed in major bleeding rates between treatment groups. Conclusion Clopidogrel remains the most frequently used second antiplatelet in patients with active cancer presenting with AMI. However, ticagrelor and prasugrel were associated with improved long-term survival without increasing bleeding risk. These findings suggest the need for further evaluation of more potent P2Y12 inhibitors in this high-risk population.

ABSTRACT Stroke remains one of the most devastating complications following transcatheter aortic valve implantation (TAVI). Although cerebral embolic protection devices (CEPDs) have emerged to mitigate patients' risks, their impact on stroke risk, as well as other clinical and neurocognitive outcomes after TAVI, remains uncertain. We aimed to assess whether CEPDs alleviate stroke risks and neurocognitive outcomes after TAVI. We systematically searched MEDLINE, Scopus, Web of Science (WOS), and the Cochrane CENTRAL from inception until May 2025. We included randomized controlled trials (RCTs) that assessed the effectiveness of CEPD compared to the control group (no CEPD) in adult patients (> 18 years) undergoing TAVI. The primary endpoint was the incidence of all‐cause stroke. In contrast, the secondary endpoints included disabling stroke, systemic bleeding, transient ischemic attack (TIA), and major adverse cardiovascular and cerebrovascular events (MACCE). Additionally, we assessed neurological outcomes, including changes in the Montreal Cognitive Assessment (MoCA) score, the National Institutes of Health Stroke Scale (NIHSS) score, and the presence of new ischemic lesions. Nine RCTs comprising 11,696 patients were included in the final analysis. The use of CEPDs showed no statistical difference in reducing all‐cause stroke compared to the control group (OR = 0.91, 95% CI [0.73–1.15], p = 0.44). Additionally, there was no significant difference in other studies' secondary outcomes, including disabling stroke, MACCE, systemic bleeding, or neurological outcomes, such as worsening NISSS, decline in MoCA score, and the presence of new ischemic lesions. The use of CEPD during TAVI showed no benefit in reducing the risks of all‐cause stroke and other neurological outcomes studied.

Abstract Aims Type 2 myocardial infarction due to myocardial oxygen supply–demand imbalance is associated with poor outcomes. There are no guidelines to inform care for these patients. The consensus on the assessment and management of type 2 myocardial infarction is gained. Methods and results An international e-Delphi study including experts in type 2 myocardial infarction identified through systematic review was conducted. Participants were asked to describe their approach to (i) definition and diagnosis, (ii) risk stratification, (iii) assessment of coronary artery disease and cardiac function, (iv) specialty management, (v) treatment and secondary prevention, and (vi) communication and rehabilitation. Statements generated in round one were circulated, with consensus defined a priori as ≥70% agreement on a 5-point Likert scale. Where no consensus was reached, statements were amended and recirculated for a final round. The response rate was 56% (38/68), 54% (37/68), and 72% (49/68) in the first, second, and third rounds, respectively. Following the first round, 67 unique statements were generated across six domains. Overall, consensus was achieved on 64% (43/67) of statements. Consensus was achieved for 42% (5/12) of statements on the diagnosis of type 2 myocardial infarction, 75% (3/4) on risk stratification, 50% (9/18) on the assessment of coronary artery disease and cardiac function, 60% (6/10), on specialty management, 100% (9/9) on treatment and secondary prevention, and 79% (11/15) on communication and rehabilitation. Conclusion Consensus was obtained across a number of domains for the assessment and management of patients with type 2 myocardial infarction. However, there was limited agreement amongst experts on the diagnostic criteria, which may benefit from refinement.

Abstract Vaccination is increasingly acknowledged as an effective preventive measure not only against specific infections, but also for the prevention of cardiovascular disease in high-risk patients. Specifically, a growing body of evidence suggests that vaccines against influenza, SARS-CoV-2, respiratory syncytial virus, herpes zoster, and other viruses significantly reduce infection and for influenza the incidence of major adverse cardiovascular events in vaccinated individuals. This clinical consensus statement examines the existing literature and accumulated evidence and offers practical clinical advice on vaccination timing and target demographics, specifically addressing complex clinical scenarios with a focus on cardiovascular conditions. It includes guidelines for vaccinating vulnerable populations such as immunosuppressed individuals, patients with congenital heart disease, and pregnant women as well as safety and potential complications of the procedure.

Background Hyperlipidemia is a major cardiovascular disease (CVD) risk factor, but there are limited data on its mortality trends in CVD over time. We assessed annual hyperlipidemia‐related CVD mortality trends in the United States, including the COVID‐19 pandemic's impact. Methods and Results Mortality data were obtained from the Centers for Disease Control and Prevention repository between 1999 and 2020 among patients ≥15 years old, using International Classification of Diseases, Tenth Revision ( ICD‐10 ) codes for hyperlipidemia (E78.0–E78.5) and CVD (I00–I99). Age‐adjusted mortality rates (AAMRs) per 1 000 000 population were standardized to the 2000 US population. Log‐linear regression models were used to evaluate mortality shifts. Average annual percentage change from 1999 to 2019 was used to project 2020 AAMRs, estimating pandemic‐attributed excess deaths. From 1999 to 2020, 483 155 hyperlipidemia‐related CVD deaths occurred. Despite a general CVD mortality decline, hyperlipidemia‐related CVD AAMRs rose from 36.33 in 1999 to 99.77 in 2019. Ischemic heart diseases (AAMR 49.39) were the leading cause, whereas hypertension had the highest mortality increase (average annual percentage change +10.23%). Mortality rates were higher in men (AAMR 104.87) and non‐Hispanic (AAMR 82.49), and rural populations (AAMR 89.98). Highest mortality was observed in Black populations (AAMR 84.35), those ≥75 years old (AAMR 646.45), and Western US regions (AAMR 96.88). During the first pandemic year, deaths exceeded projections by 10.55%, with notable increases among ages 35 to 75 (14.23%), Hispanic (17.96%), Black (14.82%), and urban (11.68%) groups. Conclusions Hyperlipidemia‐related CVD mortality has risen over the past 2 decades, further heightened by the COVID‐19 pandemic, with higher impact on men, Black Americans, the older population, and rural residents. Further study is needed to understand contributing factors and mitigate disparities.

Background Peripartum cardiomyopathy (PPCM) outcomes have been previously linked to demographic and social factors. The social vulnerability index (SVI) is a measure of social vulnerability in the United States. We explored PPCM disparities and the impact of SVI on PPCM mortality. Methods and Results Mortality from 1999 to 2020, SVI, and demographic data were obtained from CDC databases. County‐specific SVI rankings were linked to PPCM age‐adjusted mortality rates (AAMRs), allowing for a comparative analysis of AAMRs across both cumulative populations and subpopulations to identify disparities. All US counties were then stratified into low‐ and high‐SVI groups, facilitating comparison of SVI rankings by estimation of excess‐deaths per 1 000 000 person‐years attributable to greater social vulnerability and rate ratios (RR) through univariable Poisson regression. We identified a total of 1026 deaths related to PPCM between 1999 and 2020. Overall AAMR increased from 0.180 in 1999 to 0.326 in 2020. Black populations (AAMR: 1.081) and Southern US counties (AAMR: 0.444) had the highest AAMRs compared with other racial and US census groups, respectively. Higher SVI accounted for 0.172 excess deaths per 1 000 000 person‐years (RR=1.800). Among Black and White populations, higher SVI also accounted for 0.248 and 0.071 excess deaths per 1 000 000 person‐years, respectively. Similar impacts of greater social vulnerability were observed when comparing the US census regions (Northeast RR=1.609, Midwest RR=1.819, South RR=1.934, West RR=1.776). Conclusions PPCM mortality disparities exist across racial and geographic populations in the United States. A greater burden of social vulnerability is associated with higher PPCM mortality on a national level.

Antithrombotic treatment in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) poses a dilemma. We compared outcomes of dual antithrombotic therapy (DAT) (direct oral anticoagulants (DOACs)/warfarin + antiplatelets) vs triple antithrombotic therapy (TAT) (DOACs/warfarin, aspirin, and P2Y12 inhibitor) in this population. Multiple databases were searched from inception to December 17, 2023 to identify randomized controlled trials (RCTs) comparing DAT vs TAT in patients with AF and ACS. Outcomes included major adverse cardiac events (MACE), bleeding events, stroke, stent thrombosis, and myocardial infarction (MI). Relative risk and 95% confidence intervals were estimated with a random-effects model using the inverse-variance technique. We assigned I 2 > 50% as an indicator of statistical heterogeneity. p -Value <0.05 was considered significant. Ten RCTs comprising 6186 patients on TAT (female 26%, mean age 71 ± 9 years) and 6800 patients on DAT (female 27%, mean age 71 ± 9 years) were included. Patients receiving DAT experienced lower rates of bleeding events compared to those receiving TAT, with relative risks of 0.69 [0.55–0.87] ( p < 0.001), 0.65 [0.40–1.06] ( p = 0.09), and 0.62 [0.46–0.84] ( p < 0.001) for TAT durations of 3, 6, and 12 months, respectively. No difference was seen in the occurrence of MACE, MI, stroke, or stent thrombosis between DAT and TAT across all three durations of TAT. This is the largest pooled analysis comparing TAT to DAT stratified by the duration of antithrombotic therapy. Our results revealed that DAT was associated with reduced bleeding risk despite no difference in other outcomes.

Objective: Limited data exist around the receipt of palliative care (PC) in patients hospitalized with common chronic conditions. We studied the independent predictors, temporal trends in rates of PC utilization in patients hospitalized with acute exacerbation of common chronic diseases. Methods: Population-based cohort study of all hospitalizations with an acute exacerbation of heart disease (HD), cerebrovascular accident (CVA), cancer (CA), and chronic lower respiratory disease (CLRD). Patients aged ≥18 years or older between January 1, 2004, and December 31, 2017, referred for inpatient PC were extracted from the National Inpatient Sample. Poisson regression analyses were used to estimate temporal trends. Results: Between 2004 and 2017, of 91,877,531 hospitalizations, 55.2%, 13.9%, 17.2%, and 13.8% hospitalizations were related to HD, CVA, CA, and CLRD, respectively. There was a temporal increase in the uptake of PC across all disease groups. Age-adjusted estimated rates of PC per 100,000 hospitalizations/year were highest for CA (2308 (95% CI 2249–2366) to 10,794 (95% CI 10,652–10,936)), whereas the CLRD cohort had the lowest rates of PC referrals (255 (95% CI 231–278) to 1882 (95% CI 1821–1943)) between 2004 and 2017, respectively. In the subgroup analysis of patients who died during hospitalization, the CVA group had the highest uptake of PC per 100,000 hospitalizations/year (4979 (95% CI 4918–5040)) followed by CA (4241 (95% CI 4189–4292)), HD (3250 (95% CI 3211–3289)) and CLRD (3248 (95% CI 3162–3405)). Conclusion: PC service utilization is increasing but remains disparate, particularly in patients that die during hospital admission from common chronic conditions. These findings highlight the need to develop a multidisciplinary, patient-centered approach to improve access to PC services in these patients.