Cardiology and Therapy最新文献

Introduction: Patients with amyloid transthyretin (ATTR) amyloidosis typically experience rapid disease progression, poor treatment outcomes, irreversible loss of health-related quality of life (HRQoL), and premature mortality. Early diagnosis is vital. However, diagnostic delays and misdiagnosis are common due to under-recognition of early signs and symptoms.

Methods: ANTHOLOGY is an ATTR amyloidosis program, evidence generation, and quality improvement opportunity comprised of two multi-country, longitudinal, observational, real-world evidence studies: OverTTuRe (ClinicalTrials.gov identifier, NCT06355934) and MaesTTRo (NCT06465810). OverTTuRe will retrospectively extract and analyze secondary data from a broad spectrum of sources, and MaesTTRo will prospectively collect and analyze data from patient-reported outcome questionnaires, electronic health records, and insurance claims.

Planned outcomes: The primary objectives of OverTTuRe are to describe contemporary patient characteristics, treatment patterns and disease outcomes, and to characterize healthcare resource utilization (HCRU) and HRQoL in patients diagnosed with ATTR amyloidosis. Describing patient characteristics and HCRU before diagnosis is a secondary objective. The primary objectives of MaesTTRo are to describe patient characteristics, disease history and treatment patterns from diagnosis, and to prospectively define and assess the real-world effectiveness of current therapies. Secondary objectives are to compare the characteristics of patients according to the therapy received and compare the real-world effectiveness of current therapies. Exploratory objectives are to identify risk factors for disease progression and to describe healthcare costs.

Conclusions: ANTHOLOGY aims to broaden understanding of the contemporary epidemiology of ATTR amyloidosis, identify opportunities to accelerate diagnosis, and assess real-world comparative effectiveness of treatments. This knowledge will be used to define world-class patient care, improve treatment outcomes and HRQoL, inform updates to clinical practice guidelines and treatment pathways, and transform ATTR amyloidosis management through evidence aimed at improving the quality of the current standard of care TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT06355934 (OverTTuRe) and NCT06465810 (MaesTTRo).

Introduction: The aim of this study was to assess the applicability of an external control arm (ECA) approach in the clinical development of the oral factor XIa inhibitor asundexian for stroke prevention in patients with atrial fibrillation (AF), using prospectively collected data from the phase 2 PACIFIC-AF trial (NCT04218266) and real-world individual-level data from patients with AF treated with apixaban in the Optum^® de-identified Electronic Health Record data set (Optum^® EHR) 2013-2019.

Methods: To build ECAs, real-world patients meeting trial eligibility criteria were matched to patients enrolled in PACIFIC-AF. The primary outcome was the composite of International Society on Thrombosis and Haemostasis-defined major bleeding or clinically relevant non-major bleeding. Event rates were compared between PACIFIC-AF and ECAs at 85 days of trial duration and projected up to 2 years.

Results: Overall, 160,153 real-world patients met PACIFIC-AF eligibility criteria and were matched to patients from the PACIFIC-AF apixaban arm on 101 variables, with matching ratios of 1:10, 1:5, and 1:1. At day 85, the number of events for the primary outcome was 92 (3.68%) in the 1:10 ECA (2500 patients) and 6 (2.40%) in the PACIFIC-AF apixaban arm (250 patients), with incidence rates of 16.67 (90% confidence interval [CI] 13.92-19.63) and 11.10 (90% CI 4.83-19.45) per 100 person-years, respectively.

Conclusions: ECAs matching the PACIFIC-AF apixaban arm could be built from EHRs with concordant event rates for key trial endpoints. The ECA approach enabled the determination of event rates for treatment duration up to 2 years, thereby informing the asundexian pivotal phase 3 trial in AF.

Transthyretin amyloidosis (ATTR amyloidosis) is a systemic disease affecting multiple organ systems, particularly the heart and peripheral nervous system. Decades of research suggest the disease is caused by the dissociation, misfolding, and aggregation of transthyretin (TTR), resulting in extracellular deposition of amyloid fibrils in tissue and organs. If untreated, ATTR amyloidosis leads to substantial functional impairment, quality-of-life burden, and mortality. Because dissociation of the TTR tetramer is rate-limiting for aggregation and amyloid fibril formation, small molecules that bind to and stabilize the natively folded tetramer of TTR have been developed. Subunit exchange experiments demonstrated that tafamidis and acoramidis effectively slow TTR tetramer dissociation and aggregation in plasma at concentrations achieved with approved oral doses in patients with ATTR amyloidosis. In randomized controlled clinical trials, these TTR kinetic stabilizers have significantly reduced cardiomyopathy progression and improved quality of life in patients with variant or wild-type disease (tafamidis is also approved to slow polyneuropathy progression). Current availability of two kinetic stabilizers has increased interest in their pharmacological properties and clinical effects, including potential similarities and disparities. In this review, the mechanisms involved in TTR kinetic stabilization are summarized with preclinical and clinical study findings on the use of the kinetic stabilizers tafamidis and acoramidis.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have emerged as a transformative class of therapies initially developed for glycemic control in type 2 diabetes mellitus. Now, they are also getting recognized for their broader cardiometabolic effects. In this review, we discuss the mechanism of action of GLP-1 RAs, focusing on their proposed cardiometabolic impact and the key clinical trials that have demonstrated improvement in cardiovascular outcomes. GLP-1 RAs have demonstrated benefits in coronary artery disease, heart failure, blood pressure, and atrial fibrillation irrespective of type 2 diabetes mellitus status, with new possible applications in peripheral arterial disease. Findings thus far have been translated into recommendations in clinical guidelines by the American College of Cardiology, American Heart Association, European Society of Cardiology, and American Diabetes Association. As GLP-1 RAs become more prevalent in treating diabetes and patients with cardiovascular disease (CVD) or risk factors for CVD, clinicians will ultimately manage the practical aspects of patient selection, dosing, special considerations, and side effects of these medications. Ongoing and future clinical trials are expected to further define the cardiovascular role of GLP-1 RAs, expand their therapeutic indications, and solidify their place in the evolving landscape of cardiovascular care.

Subclinical atherosclerosis precedes overt cardiovascular disease and can be detected through surrogate markers such as arterial stiffness (AS) and carotid intima-media thickness (CIMT). This review examines the diagnostic and prognostic roles of AS and CIMT, highlighting their potential to improve cardiovascular risk stratification. Although traditional risk prediction models remain the cornerstone of primary prevention, they often fail to identify individuals at risk who lack conventional risk factors. Emerging evidence suggests that integrating CIMT and AS into risk assessment may improve the reclassification of individuals with intermediate risk. However, their routine use remains controversial due to methodological heterogeneity, variability in predictive value, and the prioritization of alternative imaging biomarkers such as carotid plaque or coronary artery calcium (CAC). This article critically assesses the strengths and limitations of AS and CIMT, discussing their potential utility as biomarkers, explores their application into clinical practice, and comprehensively summarizes the latest research.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disease caused by the deposition of insoluble amyloid fibrils derived from misfolded transthyretin (TTR). The treatment landscape is rapidly evolving, with disease-modifying therapies now targeting distinct steps in disease progression. Management requires both disease-modifying treatment and symptom-guided treatment of heart failure and arrhythmias, along with device therapy and consideration of advanced heart failure interventions (i.e., heart transplantation) in select patients. Therapeutic advances have significantly increased treatment possibilities, selection of appropriate therapy, switching between therapies, combination strategies, and how to monitor treatment response over time. This review summarizes available and investigational therapies for ATTR-CM and considers practical questions that guide clinical decision-making, with the goal of helping clinicians navigate the evolving therapeutic landscape.

Introduction: There is a paucity of data regarding the trends and comparative outcomes of transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR) among patients with polyvascular disease (PVD).

Methods: The Nationwide Readmissions Database (2016-2020) was queried for patients undergoing AVR. Propensity score matching was used to compare the outcomes of TAVR versus SAVR among patients with PVD, and for comparing TAVR among those with versus without PVD. The primary outcome was in-hospital mortality.

Results: The final cohort included 545,409 hospitalizations for AVR. During the study years, there was an increase in the utilization of TAVR versus SAVR among patients with PVD. Patients with PVD undergoing TAVR were older and more likely to be women compared with patients with PVD undergoing SAVR. Compared with SAVR, patients with PVD undergoing TAVR had lower odds of in-hospital mortality (adjusted odds ratio (aOR) 0.26; 95% confidence interval (CI) 0.19-0.35), acute myocardial infarction (AMI), ischemic stroke, hemorrhagic stroke, and major bleeding, but higher odds of pacemaker and non-elective 90-day readmissions (aOR 1.13; 95% CI 1.01-1.26). TAVR among patients with versus without PVD showed similar in-hospital mortality (aOR 1.10; 95% CI 0.94-1.20), while there were higher odds of AMI, ischemic stroke, and vascular complications after TAVR in patients with PVD. A higher burden of atherosclerotic vascular beds conferred higher mortality with SAVR more than with TAVR, while a higher burden of atherosclerotic vascular beds conferred a higher risk of ischemic stroke and readmissions after both TAVR and SAVR.

Conclusions: Nationwide data demonstrated that patients with PVD who undergo TAVR were associated with lower in-hospital mortality and major cardiovascular complications compared with those who undergo SAVR. Patients with PVD have similar mortality to those with no PVD undergoing TAVR, but were associated with a higher risk for complications and readmission.

Introduction: In pregnancies when congenital heart disease (CHD) is present in siblings, fetal echocardiograms (F-echo) are recommended, regardless if there was a prior level II ultrasound (LII-US) that was normal. The goal of this study was to evaluate if any diagnosis of a critical congenital heart disease (CHD) was missed in a fetus who had a sibling with CHD, when a normal LII-US was documented.

Methods: Retrospective chart review of all F-echo where the indication was sibling with CHD between January 1, 2019 and December 31, 2023 was performed. Fetuses were included if they had a LII-US that was read as normal and had a F-echo. Critical CHD was defined as CHD requiring catheterization or surgical intervention < 1 month of age.

Results: A total of 187 F-echo on fetuses who had a sibling with CHD were evaluated, of which 113 met inclusion criteria. LII-US was performed at 21.1 ± 3.3 weeks gestational age and F-echo was performed at 25.4 ± 3.1 weeks gestational age. No patient with a normal LII-US had a diagnosis of a critical CHD by F-echo (negative predictive value = 100%). Six patients that had a negative LII-US were diagnosed with non-critical CHD or cardiac issues postnatally (negative predictive value = 94.7%). F-echo correctly diagnosed two of the six missed LII-US CHD.

Conclusion: Critical CHD was not missed with a normal LII-US in this at-risk population. F-echo also missed the majority of CHD when a LII-US was read as normal. The cost/benefit of screening F-echo in fetuses with siblings with CHD should be evaluated if a normal LII-US has been performed. Larger studies are needed to determine if these findings remain consistent.

Introduction: Incomplete endothelialization (IDE) of left atrial appendage closure (LAAC) devices increases the risk of device-related thrombosis (DRT) and stroke. Insulin resistance (IR) may contribute to IDE by impairing endothelial function, but its role remains unclear. This study aimed to investigate the association between IR markers and IDE and develop a predictive model for identifying high-risk patients.

Methods: This retrospective observational study included 168 patients with nonvalvular atrial fibrillation (AF) who underwent successful LAAC at Shanghai Ninth People's Hospital between January 2022 and December 2023. IDE was assessed using transesophageal echocardiography (TEE) and cardiac computed tomography angiography (CCTA) at 6 months post-procedure. IR was evaluated using the triglyceride-glucose (TyG) index, triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-c) ratio, and metabolic score for insulin resistance (METs-IR). Logistic regression analysis was performed to identify independent predictors of IDE, and a predictive model was constructed.

Results: Among the 168 patients included in the analysis, 43 (25.5%) exhibited IDE, as determined by TEE or CCTA at 6 months post-procedure. Patients with IDE had a significantly higher body mass index, triglyceride (TG) levels, total TG/high-density lipoprotein ratio, TyG index, METs-IR index, and D-dimer levels, as well as a larger maximum LAA orifice diameter (p < 0.05). Multivariate logistic regression identified D-dimer, METs-IR, and maximum LAA orifice diameter as independent predictors of IDE. The predictive probability model incorporating these factors demonstrated high discriminatory ability (area under the curve 0.800, 95% confidence interval 0.71-0.89, p < 0.0001). The optimal predicted probability cut-off value was 0.284, achieving a sensitivity of 76.2% and a specificity of 85.2%.

Conclusion: IR markers, D-dimer levels, and LAA orifice size are significant predictors of IDE following LAAC. The logistic regression model proposed here provides an effective risk stratification tool for identifying patients at higher risk for IDE, enabling personalized anticoagulation strategies and optimizing post-procedural management. Future research should explore whether metabolic interventions can enhance endothelialization and improve long-term outcomes in patients undergoing LAAC.