Journal of the American Heart Association最新文献

Background: The Direct Oral Anticoagulant (DOAC) Score can predict bleeding risk in patients with atrial fibrillation taking DOACs; however, it lacks external validation. Therefore, this study aimed to assess the association between the DOAC Score and bleeding events in patients with atrial fibrillation who underwent transcatheter aortic valve replacement.

Methods and results: This retrospective multicenter cohort study included patients with atrial fibrillation who underwent transcatheter aortic valve replacement, as registered in a Japanese multicenter registry. The primary end point was the incidence of bleeding. Patients were categorized based on their DOAC Score: low and moderate- (≤7 points), high- (8-9 points), and very high-risk (≥10 points) groups. Among 1230 patients (mean age 84.6±5.1 years; 457 men), 465 (37.8%) received a vitamin K antagonist, and the remaining patients received DOACs. The low and moderate-, high-, and very high-risk groups included 380 (30.1%), 497 (40.4%), and 353 patients (28.7%), respectively. The 3-year cumulative incidence of all bleeding events was significantly different among the 3 groups (low and moderate risk: 6.6%, high risk: 6.9%, and very high risk: 14.0%; P<0.01). Multivariable Cox regression analysis revealed that significant increments in the DOAC Score were associated with a risk of all bleeding events at 3 years in the overall cohort (hazard ratio [HR], 1.22 [95% CI, 1.08-1.38]; P<0.01), in the DOAC cohort (HR, 1.20 [95% CI, 1.01-1.42]; P=0.04), and in the vitamin K antagonist cohort (HR, 1.25 [95% CI, 1.04-1.50]; P=0.02).

Conclusions: The DOAC Score was significantly associated with bleeding events in patients with atrial fibrillation after transcatheter aortic valve replacement, aiding in clinical decision-making for anticoagulant management.

Registration: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023585; Unique identifier: UMIN000020423.

Background: Poor adherence to chronic cardiovascular treatments can impede targeted clinical outcomes. This study estimates the potential benefits of improving adherence among patients with cardiovascular disease requiring secondary prevention in Mexico, Thailand, and China.

Methods and results: We performed Markov model simulation for patients with cardiovascular disease in 3 countries from health care and societal perspectives over a lifetime horizon. Two scenarios were compared: (1) optimal adherence based on a meta-analysis of 51 randomized controlled trials and (2) status quo. The association between adherence and cardiovascular disease outcomes derives from a dose-response meta-analysis of 4 051 338 patients. Outcomes include the accumulated number of cardiovascular events and associated costs in 2022 US dollars, life years, and quality-adjusted life years. Optimal adherence could prevent 42 (95% credible interval [CrI], 29-56) cardiovascular events in Mexico, 34 (95% CrI, 24-50) in Thailand, and 63 (95% CrI, 43-89) in China per 1000 patients over a lifetime. Incremental effectiveness per patient was 0.60 (95% CrI, 0.47-0.74) life-years in Mexico, 0.68 (95% CrI, 0.37-0.94) quality-adjusted life years in Thailand, and 0.93 (95% CrI, 0.44-1.27) quality-adjusted life years in China. Cost savings from societal perspective amounted to $412 (95% CrI, $211-$723), $316 (95% CrI, $187-$541), and $700 (95% CrI, $355-$1144) per patient for Mexico, Thailand, and China, respectively. Findings remained cost saving in deterministic and probabilistic sensitivity analyses.

Conclusions: Achieving optimal adherence in patients with cardiovascular disease requiring lipid-lowering therapy saves costs and improves health outcomes in Mexico, Thailand, and China. These findings support national health care systems implementing strategies to improve adherence in these countries.

Background: Systemic inflammatory response syndrome (SIRS) following cardiovascular interventions is associated with adverse events during hospitalization and follow-up. Mitral transcatheter edge-to-edge repair is increasingly utilized for treatment of mitral regurgitation (MR). We investigated whether SIRS following mitral transcatheter edge-to-edge repair may occur and be associated with adverse clinical outcomes.

Methods and results: A total of 158 consecutive patients with severe MR undergoing mitral transcatheter edge-to-edge repair were studied. SIRS was defined by leukocytosis (≥12 × 10⁹/L) and fever (≥38 °C) within 48 hours after intervention. Baseline inflammation was measured by absolute neutrophil and lymphocyte counts and neutrophil-lymphocyte ratio. The primary end point of major cardiovascular events was the composite of nonfatal myocardial infarction, nonfatal stroke, and all-cause death. Recurrent MR at follow-up was also recorded. The mean patient age was 80.8±8.8 years. Forty-four (27.9%) developed SIRS. Neutrophil-lymphocyte ratio correlated with onset of leukocytosis and fever (P=0.04). During a median follow-up of 12.5 (5.4-17.4) months, the primary end point occurred in 27 (17.1%) patients (6 myocardial infarction, 5 strokes, and 16 deaths). Patients with SIRS more often had severe MR (79.5% versus 62.7%, P=0.02) at follow-up. After adjustment for pertinent variables, SIRS (HR 2.73 [95% CI, 1.08-6.86]; P=0.03) was independently associated with major cardiovascular events.

Conclusions: SIRS after mitral transcatheter edge-to-edge repair is a strong independent predictor of major cardiovascular events. Closer follow-up is warranted because patients with SIRS have more severe MR at follow-up.

Background: The association between platelet endothelial cell adhesion molecule-1 (PECAM-1) with cerebral small-vessel disease and cognition in dementia-free subjects remains uninvestigated.

Methods and results: A prospective cohort of dementia-free subjects was recruited from memory clinics and followed up for 5 years. Annual neurocognitive assessments and twice-yearly brain magnetic resonance imaging scans were performed. Associations of baseline plasma PECAM-1 levels with cerebral small-vessel disease, cognitive decline (Montreal Cognitive Assessment scores and executive function Z scores), and incident dementia were evaluated. Of 213 subjects (aged 70.2±7.7 years, 51.2% men), median PECAM-1 levels were 0.790 (interquartile range, 0.645-0.955 ng/mL). Compared with the highest tertile, subjects within the lowest PECAM-1 tertile had greater cross-sectional white matter hyperintensity volume (β=4.84 [95% CI, 0.67-9.01]; P=0.023), age-related white matter change scores (β=1.39 [95% CI, 0.12-2.67]; P=0.033), and cerebral microbleeds (Adjusted risk ratio, 2.59 [95% CI, 1.19-5.62]; P=0.016). Of the 204 participants with follow-up data (median, 60.0 [interquartile range, 60.0-60.0] months), 24 (11.8%) developed incident dementia. Compared with the highest tertile, subjects within the lower tertiles of PECAM-1 had a higher risk of incident dementia (first tertile: adjusted hazard ratio [AHR], 4.52 [95% CI, 1.35-15.13]; P=0.024; second tertile: AHR, 3.28 [95% CI, 1.02-10.60]; P=0.047). The lowest PECAM-1 tertile was associated with greater progression of white matter hyperintensity volume (β=4.15 [95% CI, 0.06-8.24]; P=0.047), cerebral microbleeds (incident relative risk [IRR], 2.21 [95% CI, 1.05-4.65]; P=0.036), and decline in executive function (β=-0.45 [95% CI, -0.76 to -0.14]; P=0.004), and Montreal Cognitive Assessment (β=-1.32 [95% CI, -2.30 to -0.35]; P=0.008) scores.

Conclusions: In dementia-free subjects, lower circulating PECAM-1 levels are associated with greater cerebral small-vessel disease progression and cognitive decline, thus warranting future study as a potential therapeutic target.

Background: Subaortic stenosis (SAS) is characterized by a fibromuscular membrane located just below the aortic valve, causing fixed outflow tract obstruction. There is a paucity of studies evaluating this condition. This cohort study reviewed the contemporary characteristics and outcomes of SAS in adult patients in a single large referral center.

Methods and results: We retrospectively studied adult patients with SAS evaluated at our center during 2011 to 2022. The primary outcome was all-cause mortality and heart failure hospitalizations during follow-up, with secondary end points including recurrence of SAS and repeat surgery after initial SAS surgery. Among 484 patients with SAS, key characteristics included mean age 55±18 years, 67.5% female, left ventricular outflow tract peak velocity 352±140 cm/s and gradient 57±40 mm Hg, left ventricular ejection fraction 60%±14%, 54.8% had prior SAS surgery, and 45.1% had surgery during follow-up. Over a median follow-up of 5.5 (1.5-12.3) years, 11.5% (n=56) died, 6.8% (n=33) had heart failure hospitalizations, 8.0% (n=39) experienced SAS recurrence, and 14 (5.9%) underwent repeat SAS surgery. Multivariable analyses identified older age per 10-years (hazard ratio [HR], 1.37 [95% CI, 1.12-1.68]) and baseline New York Heart Association class (HR, 2.48 [95% CI, 1.54-3.99]) to be statistically significantly associated with the primary end point; higher body mass index, New York Heart Association class, and peak left ventricular outflow tract gradient were also statistically significantly associated with SAS recurrence and redo surgery.

Conclusions: Almost half of patients with SAS had surgery in the past or during follow-up, and a significant minority had mortality or morbidity events during follow-up. Identified prognosticators warrant further research to guide management.

Background: White matter hyperintensities (WMHs) are frequently observed on magnetic resonance imaging (MRI) in patients with cerebral amyloid angiopathy (CAA). The neuropathological substrates that underlie WMHs in CAA are unclear, and it remains largely unexplored whether the different WMH distribution patterns associated with CAA (posterior confluent and subcortical multispot) reflect alternative pathophysiological mechanisms.

Methods and results: We performed a combined in vivo MRI-ex vivo MRI-neuropathological study in patients with definite CAA. Formalin-fixed hemispheres from 19 patients with CAA, most of whom also had in vivo MRI available, underwent 3T MRI, followed by standard neuropathological examination of the hemispheres and targeted neuropathological assessment of WMH patterns. Ex vivo WMH volume was independently associated with CAA severity (P=0.046) but not with arteriolosclerosis (P=0.743). In targeted neuropathological examination, compared with normal-appearing white matter, posterior confluent WMHs were associated with activated microglia (P=0.043) and clasmatodendrosis (P=0.031), a form of astrocytic injury. Trends were found for an association with white matter rarefaction (P=0.074) and arteriolosclerosis (P=0.094). An exploratory descriptive analysis suggested that the histopathological correlates of WMH multispots were similar to those underlying posterior confluent WMHs.

Conclusions: This study confirmed that vascular amyloid β severity in the cortex is significantly associated with WMH volume in patients with definite CAA. The histopathological substrates of both posterior confluent and WMH multispots were comparable, suggesting overlapping pathophysiological mechanisms, although these exploratory observations require confirmation in larger studies.

Background: A multidisciplinary approach improves guideline-directed medical therapy (GDMT) in systolic heart failure (HF), but its efficacy in patients with HF due to cardiac sarcoidosis (CS) is unreported.

Methods and results: In a retrospective cohort study, we reviewed 848 patients from our institutional CS clinics, identifying those with a CS diagnosis, HF (LVEF < 50%) at index evaluation, and echocardiograms within 90 days and 11-36 months. Patients were stratified by participation in a pharmacist-led medication therapy management (MTM) program for GDMT optimization (MTM vs non-MTM [NMTM]) without randomization. Demographics, LVEF, GDMT (quantified by Kansas City Medical Optimization [KCMO] score), and immunosuppressive therapy were assessed. Primary outcomes included changes in KCMO score, LVEF, and cardiovascular event-free survival (unplanned HF hospitalization, LVAD/heart transplant, or death). The final cohort included 111 patients (median age 57 years, 34% female, 64% NYHA Class I-II); 43 (39%) were MTM and 68 (61%) were NMTM. Mean KCMO score was similar at index evaluation (MTM: 23.2; NMTM: 29.6, p=0.83). At follow-up (median 16 months), the KCMO score increased significantly in both groups (MTM: 23.2 to 74.8, p<0.001; NMTM: 29.6 to 58.7, p<0.001), but was higher in MTM (p=0.001). Mean LVEF trended towards higher values in MTM (44.4% vs 40.0%, p=0.05). The primary clinical outcome occurred in 1 MTM (2.3%) and 16 NMTM (23.5%) patients, with higher risk in NMTM (HR 11.97 [95%CI 1.58 - 90.54], p=0.002).

Conclusions: In this retrospective cohort study, a pharmacist-led MTM program was associated with favorable GDMT optimization and lower risk of adverse cardiovascular outcomes in CS patients with HF.

Background: Hyperlipidemia is a major cardiovascular disease (CVD) risk factor, but 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 CDC repository between 1999 and 2020 among patients ≥15 years old, using ICD-10 codes hyperlipidemia (E78.0-E78.5) and CVD (I00-I99). Age-adjusted mortality rates (AAMR) per 1,000,000 population was standardized to the 2000 US population. Log-linear regression models were used to evaluate mortality shifts. Average annual percentage change (AAPC) from 1999-2019 was used to project 2020 AAMR, 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 AAMR rose from 36.33 in 1999 to 99.77 in 2019. Ischemic heart diseases (AAMR 49.39) were the leading cause while hypertension had the highest mortality increase (AAPC +10.23%). Mortality rates were higher in males (AAMR 104.87), non-Hispanic (AAMR 82.49), and rural populations (AAMR 89.98). Highest mortality was observed in Black populations (AAMR 84.35), those ≥75 years (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 35-75 (14.23%), Hispanic (17.96%), Black (14.82%), and urban (11.68%) groups.

Conclusions: Hyperlipidemia-related CVD mortality has risen over the past two decades, further heightened by the COVID-19 pandemic, with higher impact on males, Black Americans, the elderly, and rural residents. Further study is needed to understand contributing factors and mitigate disparities.

Background: This study examined the longitudinal associations of baseline psychosocial stress subgroups with cardiovascular disease (CVD) events and whether social support, neighborhood cohesion, and physical activity modified these associations in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods and results: Data from 6,349 adults (aged: 62.2±10.2 years; 52.9% women) from the MESA study with no prior CVD in 2000-2002 were used in this analysis. Latent class analysis (LCA) was used to specify distinct psychosocial stress subgroups based on self-reported stressors stemming from respondents' neighborhood and social environment. Adjudicated CVD events (fatal and nonfatal events) were ascertained annually through the year 2019. Cox proportional hazards models were used to examine the associations between subgroup membership and CVD events. Five distinct psychosocial stress subgroups were identified via LCA and were labeled 'moderate neighborhood noise' (12.1%), 'excessive neighborhood noise' (6.4%), 'multiple high stressors' (6.3%), 'high discrimination' (21.4%), and 'optimal' (53.8%). By the year 2019, 1,121 participants had experienced a CVD event. Membership in the 'high discrimination' (HR: 1.29; 95%CI: 1.10, 1.51) subgroup was associated with higher risk of a CVD event when adjusted for sociodemographic characteristics and cardiovascular health metrics. Neither social support, neighborhood cohesion, nor physical activity modified this association (ps>0.05).

Conclusions: Distinct subgroups of individuals with high self-reported psychological distress-particularly related to discrimination and chronic stress are associated with high incident cardiovascular events.