American heart journal最新文献

Sudden cardiac arrest and death in the young is a critical public health issue. It occurs in children of any age, sex, racial or ethnic demographic, or socioeconomic status. Importantly, it can affect any individual - athlete and non-athlete alike. Prevention of sudden death in the young is of high importance not only because of the loss of a young life but also because of the substantial impact to families and to society at large. This White Paper summarizes the proceedings of a third national Think Tank on prevention of sudden cardiac death in the young. The Think Tank, which convened on January 11-12, 2024 at Duke University in Durham, NC, was organized and conducted by the Cardiac Safety Research Consortium in collaboration with a broad panel of US and international stakeholders including representatives from the United States Food and Drug Administration, medicine, academia, industry, the military, parents and sudden cardiac arrest/death prevention advocates, and the public. Primary and secondary prevention of sudden cardiac death in youth were discussed in depth with a goal of developing consensus on uniform approaches which could be applied nationally.

Cardiovascular disease remains the leading cause of mortality and healthcare expenditures in the United States. It is also a major contributor to premature mortality, years lived with disability, and rising healthcare costs around the world. Despite the availability of proven therapies and interventions that could vastly decrease the burden of cardiovascular disease and cardiometabolic conditions, their implementation is poor, with generally less than half of patients being treated with the most effective therapies. Implementation science offers promise in bridging this gap and mitigating disparities. However, even though small studies have shown that there are effective methods to improve the implementation of evidence-based therapies, these methods have not been scaled to make an impact at the level of health systems or nationally. A coordinated, multi-stakeholder approach is essential to identify barriers to implementation on a broad scale and, more critically, to develop and deploy practical solutions. The Duke Clinical Research Institute conducted an Implementation Summit entitled "Scalability, Spread, and Sustainability" to explore strategies for advancing the uptake of evidence-based interventions for cardiometabolic diseases in healthcare in the United States. This manuscript presents the participants' multi-stakeholder perspective on the steps necessary to improve the implementation of evidence-based therapies in cardiometabolic disease. Key recommendations include focused efforts on evidence generation around broad implementation strategies, dissemination of the evidence generated, uptake of evidence into usual care settings, and investment in training the current and next generations of leaders in implementation.

Many experts suspect there has been a gradual decline in cardiac auscultation skills among physicians, though no studies have examined this hypothesis. To better evaluate the long-term change in cardiac auscultation skills, we performed a repeated, cross-sectional study to analyze medical trainee performance on a cardiac auscultation simulation test over an 11-year period. Our data demonstrated a decline in simulation test scores over time among medical students. This study underscores the importance of broad investment in strategies for teaching cardiac auscultation in order to preserve and improve this valuable skill.

Background: Angiography-derived Fractional Flow Reserve (FFR) software has been developed using pressure wire based FFR as the reference, however most software requires two angiographic views ≥25 degrees apart limiting their clinical utility. This study aims to validate in a prospective multi-center registry the diagnostic performance of a novel angiography derived instantaneous wave-free ratio (Angio-iFR, Royal Philips, Amsterdam) with pressure wire-based iFR as reference.

Methods: Coronary angiograms were obtained from patients with coronary artery lesions of between 40-90% severity and both iFR and FFR measurements. The pressure wire's position was documented during contrast injection in two angiographic views. Angio-iFR/FFR was computed at this exact position by independent corelab analysts blinded to physiological data. The primary end point was the sensitivity and specificity of the Angio-iFR compared to the corresponding invasively measured iFR values. The study was powered to meet prespecified performance goals for sensitivity (75%) and specificity (80%).

Results: A total of 441 patients were enrolled in 32 centers in Europe, Japan, and the United States. Paired Angio-iFR and wire-iFR were available in 398 vessels. The mean iFR was 0.90 (standard deviation: 0.11) with 31.9% of vessels having an iFR≤0.89. Angio-iFR software showed excellent feasibility (97%), and a median analysis time of 55 seconds. The per-vessel sensitivity and specificity of Angio-iFR was 77% (95% confidence interval [CI]: 69-84%) and 49% (95%CI: 41- 54%) respectively, which fell below the performance goals.

Conclusions: Angio-iFR did not achieve prespecified diagnostic performance against pressure wire-based iFR. Further software refinements are warranted.

Trial registration: Radiographic Imaging Validation and EvALuation for Angio iFR (ReVEAL iFR), NCT0385750, https://clinicaltrials.gov/study/NCT03857503.

Background: Elevated triglycerides are an important risk factor for atherosclerosis. However, the magnitude of triglyceride lowering with currently available therapies is modest and the impact of triglyceride-lowering on atherosclerosis remains undefined. Olezarsen is an antisense oligonucleotide (ASO) targeting mRNA for apolipoprotein C-III (apoC-III), an inhibitor of triglyceride clearance.

Methods: The Essence-TIMI 73b trial (NCT05610280) is a randomized, double-blind, placebo-controlled phase 3 trial of olezarsen 50 mg or 80 mg every 4 weeks compared with placebo. The trial enrolled adults with either moderate hypertriglyceridemia (200-499 mg/dL) plus increased cardiovascular risk, or severe hypertriglyceridemia (≥500 mg/dL). The primary endpoint is the percent change in triglyceride levels from baseline to 6 months for each olezarsen dose versus pooled placebo. A coronary computed tomography angiography (CTA) substudy will examine changes in non-calcified plaque volume from baseline to 12 months.

Results: A total of 1,478 patients were randomized at 160 sites in North America and Europe. The median age is 63 (IQR 56-69) years, 39% are women, and 71% are non-Hispanic White. Overall, 60% of patients have diabetes, and 42% have atherosclerotic cardiovascular disease. At randomization, 97% were receiving lipid-lowering therapies, including 82% on a statin. The median baseline triglyceride level was 249 (195-339) mg/dL and 9% of patients had triglycerides ≥500 mg/dL at enrollment. Approximately 1000 patients completed a baseline CTA, of whom 555 (55%) have had measurable non-calcified coronary plaque and continued in the substudy.

Discussion: Targeting apoC-III to facilitate clearance of triglyceride-rich lipoproteins is a potential therapeutic strategy for lowering triglyceride levels, regressing atherosclerosis, and reducing cardiovascular risk. The phase 3 Essence-TIMI 73b trial, which has enrolled nearly 1,500 patients, including over 550 in a coronary CTA substudy, should provide key insights into the efficacy and safety of olezarsen in patients with largely moderate hypertriglyceridemia and elevated cardiovascular risk.

Trial registration: Clinicaltrials.gov: NCT05610280.

Background: Digital health interventions have potential to improve outcomes in high risk cardiac patients through remote monitoring and patient education but introduce accessibility issues among patients who lack suitable smartphones. We will evaluate the effectiveness and scalability of the TeleClinical Care Cardiac (TCC-Cardiac) platform, that aims to reduce hospital readmissions and improve adherence to care.

Methods: A pragmatic, all-comers trial with nested randomization, where patients being discharged home following an admission with acute myocardial infarction (MI) or decompensated heart failure (HF) are divided into three cohorts pragmatically, based on their access to technology. Cohort 1 participants are randomized to either the TCC-Cardiac model of care or usual care alone. The intervention includes a smartphone app, BP monitor, weight scales, and a pulse oximeter, with remote monitoring of daily inputs by clinicians. Cohort 2 participants, with incompatible mobile phones, are randomized to receive educational content by SMS (TCC-Text) or usual care alone. Cohort 3 participants with no mobile phone receive usual care alone. The primary objective is to compare six-month readmission rates (primary end point) in Cohort 1. Secondary objectives include comparing the primary end point, evaluating the cost-effectiveness and overall impact across all cohorts and interventions, and process evaluation to understand the reach, adoption, and effectiveness of the full intervention. Follow-up includes 6-month interview for Cohort 1 and data linkage for all cohorts for 12-month outcomes.

Results: The trial began in July 2021. Recruitment was slower than expected due to delays and interruptions related to COVID-19 and the final enrolment date was set for October 2023, by which time 873 participants had been enrolled: 553 in Cohort 1 (63.3%), 161 in Cohort 2 (18.4%), and 159 in Cohort 3 (18.2%). Data linkage is anticipated in May 2025, which includes a 6-month delay to ensure 12-month data will be available for all study patients, followed by the analysis of results.

Conclusions: TCC-Cardiac is the first large-scale study to assess smartphone-based messaging and remote monitoring in high-risk cardiac patients post-hospitalization. The study's pragmatic design and process evaluation aim to enhance future implementation.

Background: Among Hispanic/Latino subgroups residing in the US, disparities in cardiovascular health status remain largely uncharacterized.

Methods: This national study used the National Health Interview Survey to assess the burden of cardiometabolic risk factors (hypertension, hyperlipidemia, obesity, diabetes) and cardiovascular diseases (history of heart attack, coronary heart disease, angina, stroke) across Hispanic/Latino subgroups (Mexican, Cuban, Puerto Rican, Central/South American), and the extent to which differences are related to lifestyle factors (physical inactivity, smoking, and alcohol consumption) and/or social determinants of health (income, education, food security, and health insurance status).

Results: The weighted study population included 35,549,841 Hispanic/Latino adults (26,008 respondents). In age- and sex-adjusted models, hypertension was more common among Puerto Rican adults (OR 1.34, 95% CI: 1.12-1.60) but less common among Central/South American adults (OR 0.71, 95% CI: 0.61-0.82) compared to Mexican adults (reference group). Central/South Americans were also less likely to have obesity (OR 0.63, 95% CI: 0.57-0.70) and diabetes (OR 0.50, 95% CI: 0.42-0.61). For cardiovascular diseases, Puerto Rican adults were more likely to have angina (OR 1.69, 95% CI: 1.06-2.71), whereas Central/South Americans were less likely to have angina (OR 0.50, 95% CI: 0.30-0.84), coronary heart disease (OR 0.70, 95% CI: 0.51-0.96), and heart attack (OR 0.49, 95% CI: 0.33-0.72). Moreover, Cuban adults were less likely to have hyperlipidemia (OR 0.73, 95% CI: 0.61-0.88), obesity (OR 0.58, 95% CI: 0.49-0.70), diabetes (OR 0.44. 95% CI: 0.34-0.57) and stroke (OR 0.54, 95% CI: 0.32-0.92) Differences persisted after sequentially adjusting for lifestyle factors and social determinants of health.

Conclusion: This study used disaggregated data to demonstrate the complex landscape of cardiovascular health among Hispanic/Latino adults in the US, emphasizing the need for targeted interventions and policy efforts to reduce health inequities in this rapidly growing population.

Angina with non-obstructive coronary arteries (ANOCA) is a major cause of chronic coronary syndromes, affecting nearly half of patients with anginal symptoms who undergo invasive coronary angiography. ANOCA may lead to substantial symptom burden, increased risk of adverse cardiac events, increased healthcare utilization due to ongoing symptoms, repeat hospitalizations, and invasive testing. The pathophysiology of ANOCA often involves a variety of coronary disorders, such as coronary microvascular dysfunction, epicardial or microvascular vasospasm and endothelial dysfunction. While coronary function testing (CFT) can identify each of these specific endotypes, in current practice it is used as a second- or third-line diagnostic tool, delaying diagnosis which contributes to persistent symptoms and diminished quality of life. The ILIAS ANOCA clinical trial aims to enhance understanding and management of ANOCA through early routine CFT-guided management. After exclusion of obstructive coronary artery disease, eligible patients undergo comprehensive CFT, and will be randomized to blinding of the CFT results (control group) or disclosure of the CFT results combined with a tailored medical therapy escalation plan (intervention group). The control group will be unblinded after one year. The primary outcome is the mean difference in the within-subject change in Seattle Angina Questionnaire (SAQ) summary score between the groups at 6 months from baseline. Secondary outcomes include differences in SAQ-summary score and additional health-status and quality of life questionnaires at 12 and 24 months from baseline. Trial registration: International Clinical Trials Registry Platform identifier NL-OMON20739.

Severe hypertriglyceridemia (HTG), defined as a serum triglyceride (TG) concentration ≥500 mg/dl, is present in approximately 1 in every 500 individuals and carries direct clinical consequences, including pancreatitis, which can be life-threatening. Olezarsen is an investigational antisense oligonucleotide targeted to the mRNA for apolipoprotein C-III (apoC-III), a protein known to impair TG clearance by inhibiting lipoprotein lipase and the hepatic uptake of triglycerides and triglyceride-rich remnants. Olezarsen has been evaluated in patients with predominantly moderate HTG (150-499 mg/dl) and a rare genetic condition known as Familial Chylomicronemia Syndrome (FCS), with TG lowering effects of 53% and 44%, respectively, and reductions in pancreatitis among the FCS population. However, no dedicated trial has tested olezarsen in patients with severe HTG. In these two pivotal phase 3 trials, CORE -TIMI 72a (NCT05079919) and CORE2 -TIMI 72b (NCT05552326), over 1,000 patients with severe HTG will be randomized in a 2:1 fashion to either olezarsen (80 mg or 50 mg dose) or matching placebo. Patients will be treated for a total of 53 weeks and evaluated for the primary endpoint of percent change in TGs from baseline to 6 months compared to placebo. Pooled analyses of CORE and CORE2 will also assess olezarsen's effect on acute pancreatitis events and change in hepatic steatosis. Together, CORE -TIMI 72a (NCT05079919) and CORE2 -TIMI 72b (NCT05552326) are designed to establish the efficacy and safety of olezarsen in patients with severe HTG.