Biomedical subjects

W H Wilson Tang

Publications and source records attributed to W H Wilson Tang.

8 recordsLinked to original sources

PubMed2026

Care Models for the Genetic Evaluation of Dilated Cardiomyopathy at Sites of the DCM Consortium.

BACKGROUND: Clinical genetic evaluation for patients with dilated cardiomyopathy (DCM) is minimally implemented, and models of care are not well defined. To understand current genetic care for DCM, a systematic needs assessment was conducted. METHODS: Principal investigators of the DCM Consortium convened at the Summer Scientific Symposium in July 2025. An electronic needs assessment was conducted among the 24 principal investigators in advance to define current care models by evaluating which genetic evaluation components recommended by the Heart Failure Society of America were conducted, by whom, and the time required for each component. Descriptive statistics were generated to characterize model features. Focus group discussions explored barriers and facilitators to implementing genetic services. RESULTS: Four care models emerged from the principal investigator responses: model 1: Traditional-Synchronous (25%, n=6, requiring the most time per patient); model 2: Traditional-Asynchronous (33%, n=8); model 3: Externally Sourced (17%, n=4); and model 4: Physician/Advanced Practice Provider Conducted (25%, n=6, requiring the least time per patient). All models used genetic testing, whereas other components were implemented variably or not at all. Models 1 (15.7±4.1) and 2 (15.4±3.0) were rated more acceptable than model 4 (9.8±2.9; model 1 versus model 4; P=0.027; model 2 versus model 4; P=0.023). Notably, 88% of principal investigators used genetic information for treatment decisions, including implantable cardioverter defibrillator placement (83%; n=20) and cardiac transplantation (63%; n=15). Major facilitator themes from focus group discussions included having a genetic counselor as part of the heart failure team and developing authoritative standards directing provision of DCM genetic services. Barrier themes included operational challenges, limited personnel, clinician under-recognition, need for new service delivery models, and billing/reimbursement. CONCLUSIONS: DCM genetic care models and components were highly variable across the 24 sites of the DCM Consortium, although all sites discussed similar factors that enable or hinder the implementation of genetic services for DCM. Understanding the basis of practice model variability may provide insight to yield more scalable care approaches.

cardiomyopathy, dilated↗

PubMed2026

Racial outcomes in patients with diabetic cardiomyopathy treated with an aldose reductase inhibitor: the ARISE-HF trial.

BACKGROUND: Racial and ethnic differences in diabetic cardiomyopathy (DbCM) exist, with black and Hispanic participants showing poorer health status. It remains unclear whether these differences affect the natural progression of the disease. We aimed to evaluate disease progression in individuals with DbCM, as well as racial differences in the response to AT-001. METHODS: A total of 625 participants with DbCM were randomised to either placebo or AT-001 and followed for 15 months. The primary outcome was change in peak oxygen uptake (peak VO2) and secondary outcomes included Kansas City Cardiomyopathy Questionnaire (KCCQ) and Physical Activity Scale for the Elderly scores. Analyses were stratified by race and ethnicity (black, Hispanic, white). RESULTS: Black and Hispanic participants who received placebo experienced greater declines in peak VO2 (-0.74 and -1.67 mL/kg/min, respectively) compared with white participants (-0.23 mL/kg/min, p=0.005). AT-001 demonstrated a non-statistically significant trend towards slower declines in peak VO2 in black and Hispanic participants (-0.31 and -0.62 mL/kg/min, p=0.29, respectively). Black participants who received placebo had the largest declines in most KCCQ scores. CONCLUSION: Black and Hispanic participants with DbCM experienced faster disease progression, with black participants showing the most pronounced functional and quality of life declines. The effect of AT-001 on peak VO2 changes was not statistically significant with similar effects between racial and ethnic groups (NCT04083339). TRIAL REGISTRATION NUMBER: NCT04083339.

Aged↗

PubMed2026

A Common CD36 Variant and the Genetic Landscape of Dilated Cardiomyopathy in Individuals of African Ancestry.

IMPORTANCE: Dilated cardiomyopathy (DCM) is a major cause of heart failure that disproportionately affects individuals of African genetic ancestry (AFR), among whom familial clustering of disease is also more pronounced relative to those of European ancestry (EUR). However, established monogenic DCM genes, identified primarily in EUR populations, explain a smaller proportion of DCM cases in AFR populations. A recent study identified a common AFR-specific nonsense variant in CD36 that accounts for a substantial burden of DCM in AFR. How the risk and population impact of this variant compare with those of established genetic causes of DCM is unknown. OBJECTIVE: To compare the contribution of a CD36 nonsense variant to DCM risk with that of truncating variants in TTN and pathogenic or likely pathogenic (P/LP) variants in other established DCM genes. DESIGN SETTING AND PARTICIPANTS: Multicohort genetic association study including AFR and EUR participants with exome or genome sequence and DCM case status from four datasets: All of Us, Million Veteran Program, Penn Medicine Biobank, and the DCM Precision Medicine Study. EXPOSURE: Carrier status for TTN truncating variants, P/LP variants in 11 high confidence DCM genes, and the CD36 nonsense variant (Y325*; 0, 1, or 2 copies). MAIN OUTCOMES AND MEASURES: Odds of DCM; prevalence of risk-variant carriers among DCM cases; and population attributable fraction (PAF) for DCM. RESULTS: Among 82,623 AFR individuals across four studies, the mean age was 53.4 years and 1,625 had DCM. CD36 Y325* risk-allele homozygotes had 4.8-fold (95% CI, 3.1-7.3) increased odds of DCM, and CD36 Y325* heterozygotes had 1.4-fold (95% CI, 1.2-1.7) increased odds. TTN truncating variants also conferred elevated risk of DCM in AFR participants (OR, 8.46; 95% CI, 5.3-12.3). Among AFR DCM cases, 2.5% were CD36 homozygotes, second only to TTN truncating variants (4.3%) and exceeding all other high-confidence DCM genes combined (1.5%). In population-level analyses incorporating both heterozygous and homozygous CD36 Y325* carriers, the population-attributable fraction for CD36 (9.0%) surpassed that of TTN truncating variants (3.6%). CONCLUSIONS AND RELEVANCE: An ancestry-specific CD36 variant contributes more to DCM burden in AFR ancestry than established DCM genes, including TTN truncating variants, typically considered the most common genetic cause of DCM. These findings reshape the known genetic architecture of DCM in individuals of African ancestry and highlight the importance of representation in genomic research.

Journal Article↗

PubMed2026

Care Models for the Genetic Evaluation of Dilated Cardiomyopathy at Sites of the DCM Consortium.

BACKGROUND: Clinical genetic evaluation for patients with dilated cardiomyopathy (DCM) is minimally implemented and models of care are not defined. To understand current genetics care for DCM, a systematic needs assessment was conducted. METHODS: Principal Investigators (PIs) of the DCM Consortium convened at the Summer Scientific Symposium in July 2025. An electronic needs assessment was collected from the 24 PIs in advance to define current care models by evaluating which Heart Failure Society of America-recommended genetic evaluation components are conducted, by whom, and time required. Descriptive statistics were generated to characterize model features. Focus group discussions explored barriers and facilitators to implementing genetic services. RESULTS: Four care models emerged from the PI responses: 1 - Traditional-Synchronous (25%, n=6, requiring the most time per patient), 2 - Traditional-Asynchronous (33%, n=8), 3 - Externally Sourced (17%, n=4), and 4 - Physician/Advanced Practice Provider Conducted (25%, n=6, requiring the least time per patient). All models used genetic testing, whereas other components were implemented variably or not at all. Models 1 (15.7±4.1) and 2 (15.4±3.0) were rated more acceptable than Model 4 (9.8±2.9; 1 vs 4: p=0.027; 2 vs 4, p=0.023). Notably, 88% of PIs used genetic information for treatment decisions, including ICD placement (83%; n=20) or cardiac transplant (63%; n=15). Major facilitator themes from focus group discussions included having a genetic counselor on the HF team and developing authoritative standards directing provision of DCM genetic services. Barrier themes included operational challenges, limited personnel, clinician under-recognition, need for new service delivery models, and billing/reimbursement. CONCLUSIONS: DCM genetic care models and components were highly variable across the 24 sites of the DCM Consortium, even though all sites discussed similar factors that enable or hinder implementing genetic services for DCM. Understanding the basis of practice model variability may provide insight to yield more scalable care approaches.

clinical genetics↗

PubMed2025

Epigenetic Regulation in Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is a nonischemic heart muscle disease characterized by impaired contractility, cardiac dilation, and heart failure, with both genetic and nongenetic causes. Emerging evidence highlights epigenetic mechanisms, including deoxyribonucleic acid methylation, histone modifications, chromatin remodeling, and noncoding RNAs, as critical regulators of gene expression in DCM pathogenesis. This article explores familial DCM linked to pathogenic variants in genes like lamin A/C and titin, as well as nongenetic forms such as diabetic and autoimmune DCM. By summarizing recent discoveries, it highlights the epigenetic factors in bridging genetic and environmental influences, offering potential biomarkers and therapeutic targets for improved DCM management.

Humans↗

PubMed2025

Circulating Trimethylamine N-Oxide and Growth Rate of Abdominal Aortic Aneurysms and Surgical Risk.

IMPORTANCE: Plasma levels of the gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) are associated with prevalent abdominal aortic aneurysms (AAA) in humans and fostering of AAA progression in animal models; therapeutic targeting of TMAO production blocks AAA progression and rupture in multiple mouse models. A blood biomarker that identifies individuals at risk for incident AAA development, accelerated AAA expansion, or recommendation for surgical AAA repair could be an asset for risk stratification. OBJECTIVE: To determine whether TMAO is associated with risk for AAA development, rapid AAA expansion, and risk for recommended surgical intervention. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study using 2 independent clinical cohorts undergoing aorta imaging surveillance: a European cohort and a US cohort. Included in this study were patients undergoing serial imaging surveillance of the aorta and long-term outcome monitoring. Patients were recruited from single-center studies in Uppsala, Sweden, and Cleveland, Ohio. Study data were analyzed from October 2023 to May 2025. EXPOSURES: Plasma TMAO concentrations measured by stable isotope dilution liquid chromatography with tandem mass spectrometry. MAIN OUTCOMES AND MEASURES: The association of TMAO levels with AAA risk, fast-growing AAA (≥4.0 mm per year), and recommended surgical intervention (≥4.0 mm per year or ≥5.5 cm diameter). RESULTS: The European cohort included 237 individuals (median [IQR] age, 65 [65-73] years; 211 male [89.0%]), and the US cohort included 658 individuals (median [IQR] age, 63 [57-70] years; 523 male [79.5%]). In the European cohort, elevated circulating TMAO was significantly associated with AAA risk independent of traditional risk factors and kidney function. Moreover, elevated TMAO predicted both greater risk for fast-growing AAA (adjusted odds ratio [aOR], 2.75; 95% CI, 1.20-6.79) and recommended surgical intervention (aOR, 2.67; 95% CI, 1.24-6.09). Similar patterns were observed in the US cohort and the combined European and US cohort, with heightened circulating TMAO corresponding with significantly increased adjusted risk for fast-growing AAA (US cohort: aOR, 2.71; 95% CI, 1.53-4.80; combined cohort: aOR, 2.30; 95% CI, 1.47-3.62) and recommended surgical intervention (US cohort: aOR, 2.73; 95% CI, 1.56-4.80; combined cohort: aOR, 2.41; 95% CI, 1.55-3.74). Addition of TMAO to base models containing traditional cardiovascular risk factors resulted in significant improvement in both risk estimation for fast-growing AAA and predicting recommended surgical intervention. CONCLUSION AND RELEVANCE: Results of this cohort study suggest that elevated circulating TMAO levels were associated with increased risk of AAA and identified patients at heightened risk for fast-growing AAA and recommended surgical intervention. TMAO may help identify individuals who may benefit from more frequent surveillance imaging and early surgical intervention to prevent aortic dissection or rupture.

Humans↗

PubMed2025

Cardiac CT fractal analysis of LV noncompaction and common cardiomyopathies.

BACKGROUND: Left ventricular noncompaction (LVNC), or hypertrabeculation, is a myocardial condition that remains challenging to diagnose and differentiate from other cardiomyopathies. This study evaluated the ability of cardiac CT to differentiate between LVNC, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and controls using fractal analysis of LV trabeculae. METHODS: Subjects with LVNC, HCM, DCM, as well as controls, who underwent coronary CT angiography were included. LV trabecular structure was quantified using fractal analysis on a stack of 15 short-axis CT images. For each subject, maximum (FDmax) and average (FDglobal) fractal dimensions were reported. A subset of subjects also had clinically acquired cardiac MRI (CMR) exams for comparison. One-way ANOVA, Pearson correlation, and Bland-Altman analysis were used for statistical analysis. RESULTS: The study included 313 subjects (median age: 58.8 [48.1-68.0] years, 153 male) categorized into Control (89), LVNC (46), HCM (106), and DCM (72) cohorts. FDmax was significantly higher in LVNC (1.379 ± 0.047) than in Control (1.305 ± 0.033), HCM (1.321 ± 0.040), and DCM (1.344 ± 0.054) cohorts; all p < 0.001. Similarly, FDglobal was significantly higher in LVNC (1.279 ± 0.041) than in the other cohorts; all p < 0.05. In a subset of 132 subjects with both CT and CMR exams, fractal dimensions from the two modalities were strongly correlated (r = 0.63, p < 0.0001), with CT-derived values being higher (1.337 ± 0.049 vs. 1.262 ± 0.045, p < 0.0001). CONCLUSIONS: CT-derived fractal dimensions of LV trabecular structure were significantly higher in LVNC compared to control subjects, HCM, and DCM. CT-derived fractal dimensions strongly correlated with, but were higher than, those from cardiac MRI in the same subjects.

Humans↗

PubMed2025

Microbiota and kidney disease: the road ahead.

More than 850 million individuals worldwide, accounting for 10-15% of the adult population, are estimated to have chronic kidney disease. Each of these individuals is host to tens of trillions of microorganisms that are collectively referred to as microbiota - a dynamic ecosystem that both influences host health and is itself influenced by changes in the host. Available evidence supports the existence of functional connections between resident microorganisms and kidney health that are altered in the context of specific kidney diseases, including acute kidney injury, chronic kidney disease and renal stone disease. Moreover, promising data from preclinical studies suggest that targeting of gut microbial pathways may provide new therapeutic opportunities for the treatment of kidney disease. This Roadmap describes current understanding of the mechanisms by which microorganisms regulate host organ function, the effects of kidney disease on the gut microbiome, and how these insights may contribute to the development of microbe-targeted therapeutics. We highlight key knowledge gaps that remain to be addressed and strategies for addressing these, outlining both the promise and the potential pitfalls of leveraging our understanding of the gut microbiota to better understand and treat kidney disease.

Humans↗