Evaluation of the Hemocompatibility of the Direct Oral Anticoagulant Apixaban in Left Ventricular Assist Devices: The DOAC LVAD Study.

BACKGROUND: Patients receiving left ventricular assist device (LVAD) support require long-term anticoagulation to reduce the risk of thromboembolic complications. Apixaban is a direct oral anticoagulant that has become first-line therapy; however, its safety in LVAD recipients has not been well described. OBJECTIVES: This study sought to investigate whether, in patients with a fully magnetically levitated LVAD, treatment with apixaban would be feasible and comparable with respect to safety and freedom from the primary composite outcome of death or major hemocompatibility-related adverse events (HRAEs) (stroke, device thrombosis, major bleeding, aortic root thrombus, and arterial non-central nervous system thromboembolism) as compared with treatment with warfarin. METHODS: The DOAC LVAD (Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices) trial was a phase 2, open label trial of LVAD recipients randomized 1:1 to either apixaban 5 mg twice daily or warfarin therapy. All patients were required to take low-dose aspirin. Patients were followed up for 24 weeks to evaluate the primary composite outcome. RESULTS: A total of 30 patients were randomized: 14 patients to warfarin and 16 patients to apixaban. The median patient age was 60 years (Q1-Q3: 52-71 years), and 47% were Black patients. The median time from LVAD implantation to randomization was 115 days (Q1-Q3: 56-859 days). At 24 weeks, the primary composite outcome occurred in no patients receiving apixaban and in 2 patients (14%) receiving warfarin (P = 0.12); these 2 patients experienced major bleeding from gastrointestinal sources. CONCLUSIONS: Anticoagulation with apixaban was feasible in patients with an LVAD without an excess of HRAEs or deaths. This study informs future pivotal clinical trials evaluating the safety and efficacy of apixaban in LVAD recipients. (Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices [DOAC LVAD]; NCT04865978).

A WeChat-based Intervention, Wellness Enhancement for Caregivers (WECARE), for Chinese American Dementia Caregivers: Pilot Assessment of Feasibility, Acceptability, and Preliminary Efficacy.

BACKGROUND: Chinese American family caregivers of persons with dementia experience high rates of psychosocial distress and adverse health outcomes. Due to their immigrant and minority status, they face substantial obstacles to care and support, including stigma and misperception of dementia, limited knowledge and use of welfare and services, and poor social support. Few interventions have been developed or tested for this vulnerable population. OBJECTIVE: This study aims to pilot-test the Wellness Enhancement for Caregivers (WECARE) intervention, a culturally tailored program delivered via WeChat, a social media app highly popular in the Chinese population. The 7-week WECARE was designed specifically for Chinese American dementia caregivers to improve their caregiving skills, reduce stress, and enhance psychosocial well-being. Feasibility, acceptability, and preliminary efficacy of the WECARE were assessed in this pilot. METHODS: A total of 24 Chinese American family caregivers of persons with dementia were recruited for a pre-post 1-arm trial of the WECARE. By subscribing to the WECARE official account, participants received interactive multimedia programs on their WeChat account multiple times a week for 7 weeks. A backend database automatically delivered program components and tracked user activities. Three online group meetings were organized to facilitate social networking. Participants completed a baseline and a follow-up survey. Feasibility was assessed by the follow-up rate and curriculum completion rate; acceptability was assessed by user satisfaction and perceived usefulness of the program; and efficacy was assessed with pre-post differences in 2 primary outcomes of depressive symptoms and caregiving burden. RESULTS: The intervention was completed by 23 participants with a retention rate of 96%. Most of them (n=20, 83%) were older than 50 years and the majority (n=17, 71%) were female. The backend database revealed that the mean curriculum completion rate was 67%. Participants also reported high rates of user satisfaction and perceived usefulness of the intervention and high ratings of weekly programs. The intervention led to significant improvement in participants' psychosocial health outcomes; their depressive symptoms reduced from 5.74 to 3.35 with an effect size of -0.89 and caregiving burden decreased from 25.78 to 21.96 with an effect size of -0.48. CONCLUSIONS: This pilot study suggests that WeChat-based WECARE intervention was feasible and acceptable; it also demonstrated initial efficacy in improving psychosocial well-being in Chinese American dementia caregivers. Further research with a control group is needed to assess its efficacy and effectiveness. The study highlights the need for more culturally appropriate mobile health interventions for Chinese American family caregivers of persons with dementia.

Association between proteomic biomarkers and myocardial fibrosis measured by MRI: the multi-ethnic study of atherosclerosis.

BACKGROUND: Cardiac magnetic resonance imaging (CMR) determines the extent of interstitial fibrosis, measured by increased extracellular volume (ECV), and replacement fibrosis with late gadolinium myocardial enhancement (LGE). Despite advances in detection, the pathophysiology of subclinical myocardial fibrosis is incompletely understood. Targeted proteomic discovery technologies enable quantification of low abundance circulating proteins to elucidate cardiac fibrosis mechanisms. METHODS: Using a cross-sectional design, we selected 92 LGE+ cases and 92 LGE- demographically matched controls from the Multi-Ethnic Study of Atherosclerosis. Similarly, we selected 156 cases from the highest ECV quartile and matched with 156 cases from the lowest quartile. The plasma serum proteome was analyzed using proximity extension assays to determine differential regulation of 92 proteins previously implicated with cardiovascular disease. Results were analyzed using volcano plots of statistical significance vs. magnitude of change and Bayesian additive regression tree (BART) models to determine importance. FINDINGS: After adjusting for false discovery, higher ECV was significantly associated with 17 proteins. Using BART, Plasminogen activator inhibitor 1, Insulin-like growth factor-binding protein 1, and N-terminal pro-B-type natriuretic peptide were associated with higher ECV after accounting for other proteins and traditional cardiovascular risk factors. In contrast, no circulating proteins were associated with replacement fibrosis. INTERPRETATIONS: Our results suggest unique circulating proteomic signatures associated with interstitial fibrosis emphasizing its systemic influences. With future validation, protein panels may identify patients who may develop interstitial fibrosis with progression to heart failure. FUNDING: This research was supported by contracts and grants from NHLBI, NCATS and the Inova Heart and Vascular Institute.

Sex-Related Differences in Patient Characteristics, Hemodynamics, and Outcomes of Cardiogenic Shock: INOVA-SHOCK Registry.

Background: Little is known about sex-related differences in outcomes of patients with cardiogenic shock (CS) treated within a standardized team-based approach (STBA). Methods: We evaluated 520 consecutive patients (151 women and 369 men) with CS due to acute myocardial infarction (AMI) and heart failure (HF) in a single-center registry (January 2017-December 2019) and examined outcomes according to sex and CS phenotype. The primary outcome was in-hospital mortality. Secondary outcomes included major adverse cardiac events, 30-day mortality, major bleeding, vascular complications, and stroke. Results: Women with AMI-CS had higher baseline acuity (CardShock score: female [F]: 5.5 vs male [M]: 4.0; P = .04). Women with HF-CS more often presented with cardiac arrest (F: 12.4% vs M: 2.4%; P< .01) and had higher rates of vasopressor use (F: 70.8% vs M: 58.0%; P = .04) and mechanical circulatory support (F: 46.1% vs M: 32.5%; P = .04). There were no sex-related differences in in-hospital mortality for AMI-CS (F: 45.2% vs M: 36.9%; P = .28) and HF-CS (F: 28.1% vs M: 24.5%; P = .56). Women with HF-CS experienced higher rates of major bleeding (F: 25.8% vs M: 13.7%; P = .02) and vascular complications (F: 15.7% vs M: 6.1%; P = .01). However, female sex was not an independent predictor of these complications. No sex differences in survival were noted at 1 year. Conclusions: Within an STBA, although women with AMI-CS and HF-CS presented with higher acuity, they experienced similar in-hospital mortality, major adverse cardiac events, 30-day mortality, stroke, and 30-day readmissions as men. Further research is needed to better understand the extent to which historical differences in CS outcomes can be mitigated by an STBA.

Circulating microRNAs in cellular and antibody-mediated heart transplant rejection.

BACKGROUND: Noninvasive monitoring of heart allograft health is important to improve clinical outcomes. MicroRNAs (miRs) are promising biomarkers of cardiovascular disease and limited studies suggest they can be used to noninvasively diagnose acute heart transplant rejection. METHODS: The Genomic Research Alliance for Transplantation (GRAfT) is a multicenter prospective cohort study that phenotyped heart transplant patients from 5 mid-Atlantic centers. Patients who had no history of rejection after transplant were compared to patients with acute cellular rejection (ACR) or antibody-mediated rejection (AMR). Small RNA sequencing was performed on plasma samples collected at the time of an endomyocardial biopsy. Differential miR expression was performed with adjustment for clinical covariates. Regression was used to develop miR panels with high diagnostic accuracy for ACR and AMR. These panels were then validated in independent samples from GRAfT and Stanford University. Receiver operating characteristic curves were generated and area under the curve (AUC) statistics calculated. Distinct ACR and AMR clinical scores were developed to translate miR expression data for clinical use. RESULTS: The GRAfT cohort had a median age of 52 years, with 35% females and 45% Black patients. Between GRAfT and Stanford, we included 157 heart transplant patients: 108 controls and 49 with rejection (50 ACR and 38 AMR episodes). After differential miR expression and regression analysis, we identified 12 miRs that accurately discriminate ACR and 17 miRs in AMR. Independent validation of the miR panels within GRAfT led to an ACR AUC 0.92 (95% confidence interval [CI]: 0.86-0.98) and AMR AUC 0.82 (95% CI: 0.74-0.90). The externally validated ACR AUC was 0.72 (95% CI: 0.59-0.82). We developed distinct ACR and AMR miR clinical scores (range 0-100), a score ≥ 65, identified ACR with 86% sensitivity, 76% specificity, and 98% negative predictive value, for AMR score performance was 82%, 84% and 97%, respectively. CONCLUSIONS: We identified novel miRs that had excellent performance to noninvasively diagnose acute rejection after heart transplantation. Once rigorously validated, the unique clinical ACR and AMR scores usher in an era whereby genomic biomarkers can be used to screen and diagnose the subtype of rejection. These novel biomarkers may potentially alleviate the need for an endomyocardial biopsy while facilitating the initiation of targeted therapy based on the noninvasive diagnosis of ACR or AMR.

Cardiogenic Shock From Heart Failure Versus Acute Myocardial Infarction: Clinical Characteristics, Hospital Course, and 1-Year Outcomes.

BACKGROUND: Little is known about clinical characteristics, hospital course, and longitudinal outcomes of patients with cardiogenic shock (CS) related to heart failure (HF-CS) compared to acute myocardial infarction (AMI; CS related to AMI [AMI-CS]). METHODS: We examined in-hospital and 1-year outcomes of 520 (219 AMI-CS, 301 HF-CS) consecutive patients with CS (January 3, 2017-December 31, 2019) in a single-center registry. RESULTS: Mean age was 61.5±13.5 years, 71% were male, 22% were Black patients, and 63% had chronic kidney disease. The HF-CS cohort was younger (58.5 versus 65.6 years, P<0.001), had fewer cardiac arrests (15.9% versus 35.2%, P<0.001), less vasopressor utilization (61.8% versus 82.2%, P<0.001), higher pulmonary artery pulsatility index (2.14 versus 1.51, P<0.01), lower cardiac power output (0.64 versus 0.77 W, P<0.01) and higher pulmonary capillary wedge pressure (25.4 versus 22.2 mm Hg, P<0.001) than patients with AMI-CS. Patients with HF-CS received less temporary mechanical circulatory support (34.9% versus 76.3% P<0.001) and experienced lower rates of major bleeding (17.3% versus 26.0%, P=0.02) and in-hospital mortality (23.9% versus 39.3%, P<0.001). Postdischarge, 133 AMI-CS and 229 patients with HF-CS experienced similar rates of 30-day readmission (19.5% versus 24.5%, P=0.30) and major adverse cardiac and cerebrovascular events (23.3% versus 28.8%, P=0.45). Patients with HF-CS had lower 1-year mortality (n=123, 42.6%) compared to the patients with AMI-CS (n=110, 52.9%, P=0.03). Cumulative 1-year mortality was also lower in patients with HF-CS (log-rank test, P=0.04). CONCLUSIONS: Patients with HF-CS were younger, and despite lower cardiac power output and higher pulmonary capillary wedge pressure, less likely to receive vasopressors or temporary mechanical circulatory support. Although patients with HF-CS had lower in-hospital and 1-year mortality, both cohorts experienced similarly high rates of postdischarge major adverse cardiovascular and cerebrovascular events and 30-day readmission, highlighting that both cohorts warrant careful long-term follow-up. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03378739.

Social media-based intervention to promote HBV screening and liver cancer prevention among Korean Americans: Results of a pilot study.

OBJECTIVE: In United States, Asian Americans are 10 times more likely to have hepatitis B virus (HBV) infection than Whites. Asian immigrants with limited English proficiency face extra barriers to HBV screening and many are unaware of the infectious status. This study aimed to evaluate a social media-based intervention to promote HBV screening and liver cancer prevention among Korean Americans (KA) with limited English proficiency. METHODS: Our community-academia partnership developed the "Lets talk about liver cancer" mHealth program by adapting a CDC media campaign. The program consisted of culturally tailored short video clips and pictorial messages and was delivered over 4 weeks to the participants via the popular Korean social media app, Kakao Talk. A total 100 KA living in greater Washington DC metropolitan were recruited via social media networks and completed this pre-post pilot study. RESULTS: Out of the 100 participants of KA, 56 were female, mean age was 60, and most have lived in the U.S. for more than 20 years, 84% had limited English proficiency, and 21% had a family history of HBV infection or liver cancer. After 4-week intervention, 95% completed the follow-up survey. Participants reported significant improvements in HBV-related knowledge, liver cancer prevention knowledge, perceived benefits of HBV testing, perceived risks of HBV infection, injunctive norms of HBV testing, and self-efficacy of HBV testing. CONCLUSIONS: The Kakao Talk-based liver cancer prevention program for KAs was feasible and effective. We advocate for community-academia partnership to develop and implement culturally appropriate and social media-based interventions for underserved immigrants.

COVID-19 Symptom Monitoring and Social Distancing in a University Population.

This paper reports on our efforts to collect daily COVID-19-related symptoms for a large public university population, as well as study relationship between reported symptoms and individual movements. We developed a set of tools to collect and integrate individual-level data. COVID-19-related symptoms are collected using a self-reporting tool initially implemented in Qualtrics survey system and consequently moved to .NET framework. Individual movement data are collected using off-the-shelf tracking apps available for iPhone and Android phones. Data integration and analysis are done in PostgreSQL, Python, and R. As of September 2020, we collected about 184,000 daily symptom responses for 20,000 individuals, as well as over 15,000 days of GPS movement data for 175 individuals. The analysis of the data indicates that headache is the most frequently reported symptom, present almost always when any other symptoms are reported as indicated by derived association rules. It is followed by cough, sore throat, and aches. The study participants traveled on average 223.61 km every week with a large standard deviation of 254.53 and visited on average 5.77 ± 4.75 locations each week for at least 10 min. However, there is no evidence that reported symptoms or prior COVID-19 contact affects movements (p > 0.3 in most models). The evidence suggests that although some individuals limit their movements during pandemics, the overall study population do not change their movements as suggested by guidelines.

Association of coronary artery calcification and thoracic aortic calcification with incident peripheral arterial disease in the Multi-Ethnic Study of Atherosclerosis (MESA).

AIMS: The association of subclinical atherosclerotic disease in the coronary arteries and thoracic aorta with incident peripheral arterial disease (PAD) is unknown. We investigated the association between coronary artery calcium score (CACs) and thoracic aortic calcium score (TACs) with incident clinical and subclinical PAD. METHODS AND RESULTS: The Multi-Ethnic Study of Atherosclerosis (MESA) recruited 6814 men and women aged 45-84 from four ethnic groups who were free of clinical cardiovascular disease at enrolment. Coronary artery calcium score and thoracic aortic calcium score were measured from computed tomography scans. Participants with a baseline ankle-brachial index (ABI) ≤0.90 or >1.4 were excluded. Abnormal ABI was defined as ABI ≤0.9 or >1.4 at follow-up exam. Multivariable logistic regression and Cox proportional hazards models were used to test the associations between baseline CACs and TACs with incident abnormal ABI and clinical PAD, respectively. A total of 6409 participants (female: 52.8%) with a mean age of 61 years were analysed. Over a median follow-up of 16.7 years, 91 participants developed clinical PAD. In multivariable analysis, each unit increase in log (CACS + 1) and log (TACs + 1) were associated with 23% and 13% (P < 0.01for both) higher risk of incident clinical PAD, respectively. In 5725 (female: 52.6%) participants with an available follow-up ABI over median 9.2 years, each 1-unit increase in log (CACs + 1) and log (TACs + 1) were independently associated with 1.15-fold and 1.07-fold (P < 0.01for both) higher odds of incident abnormal ABI, respectively. CONCLUSION: Higher baseline CACs and TACs predict abnormal ABI and clinical PAD independent of traditional cardiovascular risk factors and baseline ABI.

Acculturation Strategies and Symptoms of Depression: The Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study.

Using latent class analysis, we previously identified three acculturation strategies employed by South Asian immigrants in the US. Members of the Separation class showed a preference for South Asian culture over US culture, while members of the Assimilation class showed a preference for US culture, and those in the Integration class showed a similar preference for South Asian and US cultures. The purpose of this study was to examine associations between these acculturation strategies and symptoms of depression, a common yet underdiagnosed and undertreated mental disorder. We used data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study (n = 856). Data were collected between October 2010 and March 2013 in the San Francisco Bay Area and Chicago. Depressive symptoms were assessed using the CES-D Scale. Applying a simple new method to account for uncertainty in class assignment when modeling latent classes as an exposure, we found that respondents in the Separation class had more depressive symptoms than those in the Integration class, but only after taking into account self-reported social support (b = 0.11; p = 0.05). There were no differences in depressive symptoms among those in the Assimilation class vs. those in the Integration class (b = -0.06; p = 0.41). Social support may protect against elevated symptoms of depression in South Asian immigrants with lower levels of integration into US culture.

Acculturation Strategies Among South Asian Immigrants: The Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study.

In the past, epidemiologic research on acculturation and health has been criticized for its conceptual ambiguity and simplistic measurement approaches. This study applied a widely-used theoretical framework from cross-cultural psychology to identify acculturation strategies among South Asian immigrants in the US and to examine sociodemographic correlates of acculturation strategies. Data were from the Mediators of Atherosclerosis in South Asians Living in America study. We used latent class analysis to identify groups of individuals that were similar based on cultural attitudes and behaviors. We used latent class regression analysis to examine sociodemographic correlates of acculturation strategies. We found that South Asian immigrants employed three acculturation strategies, including separation (characterized by a relatively high degree of preference for South Asian culture over US culture), assimilation (characterized by a relatively high degree of preference for US culture over South Asian culture), and integration (characterized by a similar level of preference for South Asian and US cultures). Respondents with no religious affiliation, those with higher levels of income, those who lived a greater percentage of their lives in the US, and those who spoke English well or very well were less likely to use the separation strategy than the assimilation or integration strategies. Using epidemiologic cohort data, this study illustrated a conceptual and methodological approach that addresses limitations of previous research on acculturation and health. More work is needed to understand how the acculturation strategies identified in this study affect the health of South Asian immigrants in the US.