Journal of the American College of Cardiology最新文献

Background: Timely diagnosis and treatment are critical to reduce morbidity and mortality for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). Limited existing data suggest underdiagnosis of ATTR-CM and inequity in predictors of diagnosis patterns.

Objective: This study sought to describe the time from heart failure (HF) diagnosis to ATTR-CM diagnosis and identify predictors for delayed diagnosis of ATTR-CM.

Methods: This retrospective cohort study used Veterans Health Administration (VHA) data. We identified patients with HF and ATTR-CM diagnosed between 2016 and 2022 using an algorithm based on diagnoses and medications. The primary outcome was the time to diagnosis of ATTR-CM and was defined as the number of days between each patient's first HF diagnosis and their first ATTR-CM diagnosis. We also evaluated the number of days between first HF hospitalization or first loop diuretic prescription and ATTR-CM diagnosis. We used multivariable logistic regression to assess demographic, clinical, and socioeconomic predictors of time to ATTR-CM diagnosis using >6 months as a meaningful delay.

Results: A total of 2,557 patients with HF and ATTR-CM were identified. The mean age at the time of ATTR-CM diagnosis was 81 years. Most veterans were male (2,544; 99.5%) and White (1,440; 56%). The median time to diagnosis to ATTR-CM was 490 days. For the 1,882 veterans with a loop diuretic prescription before ATTR-CM diagnosis, the median time between initial loop prescription and ATTR-CM diagnosis was 835 days (Q1-Q3: 250-1850). Across Department of Veterans Affairs sites, the median number of days to diagnosis ranged from 169 to 1,070 days. After adjustment, Black race (OR: 0.71; 95% CI: 0.57-0.88) and older age (OR: 0.66; 95% CI: 0.59-0.73) were associated with a shorter time to diagnosis, whereas a history of atrial fibrillation (OR: 1.21; 95% CI: 1.00-1.45), coronary artery disease (OR: 1.38; 95% CI: 1.15-1.64), or chronic kidney disease (OR: 1.79; 95% CI: 1.50-2.15) was associated with longer time to diagnosis.

Conclusions: There are clinically important delays between incident HF and diagnosis of ATTR-CM. Carrying a diagnosis of atrial fibrillation, coronary artery disease, or chronic kidney disease was associated with a longer delay to diagnosis. These findings uncover an opportunity for clinicians to consider concomitant ATTR-CM in patients with alternate etiologies for their cardiomyopathy, as expediting evaluation for ATTR-CM following HF diagnosis is critical to reduce the morbidity of this progressive condition.

Background: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) remain at risk of cerebrovascular events even when in sinus rhythm (SR), yet the majority of these patients are unrecognized.

Objectives: This study sought to identify patients in SR at high risk of cerebrovascular events.

Methods: We analyzed patients diagnosed with ATTR-CM between January 2003 and December 2023 at the UK National Amyloidosis Centre. Left atrial (LA) function was assessed using speckle-tracking strain echocardiography. Atrial electromechanical dissociation (AEMD) was defined as SR on electrocardiogram with absent left atrial strain contraction (LASc). Patients in SR were stratified according to LASc tertiles. The primary outcome was a cerebrovascular event defined as stroke or transient ischemic attack (TIA), whichever occurred first. The secondary outcome was development of atrial fibrillation (AF). Death was treated as a competing event.

Results: The study comprised 2,310 patients with ATTR-CM, of which 873 patients were in SR and not receiving anticoagulation (age 77 years, 82% male, 61% wild type, CHA₂DS₂-VASc 4). AEMD was present in 115 patients (13.2%). Of the patients in SR, over a median of 34 months (Q1-Q3: 18-54 months), 269 patients (30.8%) developed incident AF and 85 (9.7%) experienced stroke/TIA. Patients with baseline AF receiving anticoagulation had a rate of stroke or TIA of 0.7 per 100 person-years. AEMD was associated with a 2.4-fold higher incident AF and 3-fold higher risk of stroke or TIA compared with SR with LA mechanical contraction (8.7 vs 2.5 per 100 person-years, respectively, for stroke or TIA), independent of CHA₂DS₂-based scores and markers of disease severity. Among 758 patients in SR without AEMD, LASc tertiles (<4%, 4%-7%, >7%) exhibited an independent association with 1-year risk of stroke or TIA, with LASc <4% being associated with 10-fold increased risk compared to LASc >7%. This association was consistent after adjustment for NAC stage and prior cerebrovascular events. Adding LASc tertiles to CHA₂DS₂-VASc or CHA₂DS₂-VA significantly improved model fit and risk reclassification at 1 year.

Conclusions: LA dysfunction, particularly AEMD and severely impaired LASc, is associated with increased cerebrovascular events in ATTR-CM. Using LAS analysis may refine risk stratification and help identify patients with ATTR-CM in SR who might potentially benefit from intensified extended rhythm monitoring or prophylactic anticoagulation.

Background: Atrial fibrillation (AF) is heritable and its complex underlying genetic substrate is gradually being unraveled.

Objectives: We sought to explore the impact of disease-causing cardiomyopathy variants on the risk of AF after adjustment for incident ventricular cardiomyopathy and clinical heart failure in 2 cohort studies (UK Biobank [UKB] and All of Us [AoU]) and evaluate the utility of polygenic risk scores (PRS) to further discern the risk of atrial and ventricular phenotypes in carriers.

Methods: Cox regression was used to evaluate for associations between disease-causing variants within genes for 3 cardiomyopathies (dilated cardiomyopathy [DCM], hypertrophic cardiomyopathy [HCM], and arrhythmogenic right ventricular cardiomyopathy) and AF. Disease-specific PRSs for AF, DCM, and HCM stratified study participants into quintiles. A HR random-effects meta-analysis was performed using the DerSimonian-Laird method. The Kaplan-Meier method was used to ascertain cumulative incidence from birth to 75 years of age.

Results: Among 655,796 individuals from UKB and AoU, presence of a disease-causing variant was associated with an increased AF hazard (HR: 1.73; 95% CI: 1.59-1.89; P < 0.001), including after adjustment for incident ventricular cardiomyopathy or clinical heart failure (adjusted to HR: 1.55; 95% CI: 1.46-1.64, P < 0.001). The cumulative AF risk for study participants with a putative disease-causing rare variant and a PRS_AF within the top-risk quintile ranged from 32.5% (UKB) to 32.4% (AoU) relative to 9.8% (UKB) and 11.0% (AoU) for individuals without a putative disease-causing variant and a PRS_AF within the lowest-risk quintile. The absolute cumulative cardiomyopathy risk among study participants with both a putative disease-causing variant and a disease-specific PRS within the top-risk quintile ranged from 5.9% (UKB) to 15.2% (AoU) for DCM and from 11.7% (UKB) to 19.1% (AoU) for HCM.

Conclusions: Genetic variants that cause cardiomyopathy also increase the risk of AF, even in individuals without heart failure or overt ventricular disease. Combining disease-specific PRSs with these variants helps identify whether a person is more likely to develop atrial or ventricular disease. Although discovered as causes of cardiomyopathy, these genes often have an equal or greater impact on the risk of AF.

Background: Coronary artery disease (CAD) polygenic risk scores (PRS) may identify individuals at elevated genetic risk "flying under the radar" in contemporary practice. The aims of the PROACT (Polygenic Risk Based Detection and Treatment of Subclinical Coronary Atherosclerosis) trials are to prospectively identify these individuals, quantify subclinical coronary plaque, and slow its progression with pharmacologic interventions.

Objectives: The aim of this study is to report interim feasibility and implementation findings from PROACT, a genotype-first, biobank-enabled trial, characterizing eligibility yield, callback engagement, and subclinical coronary atherosclerosis on coronary computed tomographic angiography among individuals with high CAD PRS.

Methods: Within a hospital-based biobank, adults 40 to 75 years of age with high CAD PRS, without cardiovascular disease, and not on lipid-lowering therapy were invited. The authors characterize 2,495 eligible individuals with high CAD PRS, report on the feasibility and early operational outcomes of a genotype-first callback strategy for a clinical trial in the first 1,314 invited, and describe plaque prevalence by age and sex in the first 204 participants using coronary computed tomographic angiography.

Results: Among 64,092 genotyped participants, 2,495 (3.9%) were eligible and had high CAD PRS despite low clinical risk (median 10-year pooled cohort equations risk for atherosclerotic cardiovascular disease 3%; Q1-Q3: 1%-8%). Recruitment showed high engagement: among 1,314 invited individuals, 283 (21.5%) opted in, and 204 (15.5%) completed baseline imaging. Compared with participants who did not opt in, those who opted in had higher specialty care engagement and lived closer to the study site. Analysis of the first 204 participants enrolled by January 31, 2025 (mean age 56.3 ± 8.5 years, 69% women), showed that despite the low clinical risk and favorable cardiovascular health (mean Life's Essential 8 score 73.3 ± 11.5 vs the U.S. average of ∼65), one-half the participants (102 of 204) had subclinical plaque. Subclinical plaque prevalence was 76.2% in men and 38.3% in women and was high across age groups.

Conclusions: These exploratory findings highlight the feasibility of implementing genotype-first recruitment for prevention trials and reveal a large proportion of "silent" high-genetic risk individuals with subclinical plaque for whom pharmacotherapy could be beneficial but who remain undetected by standard clinical assessments. (Polygenic Risk Based Detection of Subclinical Coronary Atherosclerosis and Change in Cardiovascular Health [PROACT 1], NCT05819814; Polygenic Risk Based Detection of Subclinical Coronary Atherosclerosis and Intervention With Statin and Colchicine [PROACT 2], NCT05850091).

Background: Long-term mortality rates among postdischarge acute coronary syndrome (ACS) patients remain substantial. The temporal evolution and cause-specific drivers of this residual risk remain incomplete.

Objectives: This study aimed to comprehensively investigate the cumulative incidence of cardiovascular (CV) and non-CV mortality after ACS discharge using a competing-risks framework.

Methods: In this multicenter cohort study, we analyzed data from the China Cardiovascular Association Database-Chest Pain Center. Mortality outcomes were ascertained through linkage with the Chinese Center for Disease Control and Prevention Cause of Death Reporting System via national mortality surveillance. Eligible patients were aged 18 years or older with a discharge diagnosis of ACS between January 2018 and December 2021. The primary outcome was all-cause mortality. Causes of death were categorized as CV or non-CV, which were analyzed as competing events. Cumulative incidence and landmark analysis at 12 months were conducted to evaluate temporal mortality patterns. Multivariate competing risks regression (Fine and Gray model) was used to identify predictors associated with the cause-specific mortality. Subgroup analyses were conducted across age, sex, and ACS subtypes.

Results: Of 1,562,956 eligible patients, 1,074,289 (68.7%) were men, and the mean age was 63.8 ± 12.3 years. The competing risks analysis revealed that CV death was the primary driver of mortality at 1-month discharge (1.24% vs 0.26% for non-CV); yet, non-CV mortality showed a higher relative growth than CV mortality after 12-month discharge. Ischemic heart disease (68.5%) was the predominant CV death, whereas non-CV death was dominated by malignancy (38.3%) and chronic pulmonary disease (15.8%). Age ≥65 years (subdistribution HR [sHR]: 3.78; 95% CI: 3.72-3.849), chronic kidney disease (sHR: 2.07; 95% CI: 2.03-2.11), and chronic heart failure (sHR: 1.99; 95% CI: 1.96-2.02) were leading predictors of death. Lipid-lowering therapy was associated with lower risks of all-cause, CV, and non-CV death.

Conclusions: This national study demonstrates a transition in post-ACS mortality from CV to non-CV causes over time, with malignancy emerging as the leading cause of late-term death. These findings necessitate moving beyond traditional secondary prevention toward integrated survivorship care that addresses the full spectrum of competing risks.