The Asian neTwork for Translational Research and Cardiovascular Trials (ATTRaCT) is a programme led by A*STAR to deepen our understanding of cardiovascular (CV) disease progression in heart failure (HF).
For the first time, the ATTRaCT platform integrates top expertise in CV clinical and biomedical sciences across the nation, bringing together A*STAR research institutes (Singapore Bioimaging Consortium, Genome Institute of Singapore, Singapore Immunology Network, Institute of Molecular & Cell Biology) with the two national heart institutions (National Heart Centre, Singapore & National University Heart Centre, Singapore) as well as academic institutions (National University of Singapore, Duke-NUS Graduate Medical School).
With more than 1,000 patients, the study promises to be the most extensive ever done in Singapore on the subject. This multi-agency effort means the study will be able to benefit from each one's expertise and make a great impact on HF.
Heart failure is the final common pathway of cardiovascular (CV) diseases and leading cause of CV hospitalizations in Singapore and worldwide, with a mortality rate that rivals most cancers (>50% mortality at 5 years). Also similar to cancer, HF is a staged disease where early detection and treatment are vital for prevention of disease progression from Stage A (risk factors) to Stage B (subclinical structural heart disease) and Stage C (symptomatic HF). Cardiac imaging is critical for the detection of early subclinical disease. There is limited understanding of the mechanisms underlying disease progression and effective therapies are limited, particularly for the half of the HF population with preserved ejection fraction (HFPEF or “diastolic HF”) for which there is no effective therapy to date (in contrast to HF with reduced ejection fraction [HFREF] or “systolic HF”).
Our overall aim is to build on Singapore’s competitive advantages in advanced cardiac imaging, genetic and molecular studies to develop an integrated “one-stop” platform spanning from human to large and small animal models, dedicated to deepening our understanding of CV disease progression, discovery of new targets and repurposing of drugs.
ATTRaCT exploits data from the existing ASIAN-HF study which involves about 50 sites in 11 countries.
- First and only academic led pan-Asia Cardiovascular network
- Including China, India, Indonesia, Japan, Korea
- Prospective detailed trial-quality data with extensive echo, ECG and DNA
- Longitudinal FU for outcomes including hospitalizations, deaths, adjudicated causes
- Aiming for 8,000 patients and has already recruited 3,000 in 1 year
- Additional 1000 patients in Singapore are already recruited and providing biomarkers and echocardiographic data from which we have ample preliminary evidence to support our specific hypotheses
- Plus 1000 community-based controls which provide a multi-ethnic Asian reference not available anywhere else
Specifically we want to address the following questions:
- Why is the lean diabetic Asian phenotype prone to early heart failure?
- Can we detect preclinical disease before the onset of clinical heart failure?
- What are specific predisposing factors for the different heart failure phenotypes?
- What are specific underlying proteomic and/or immunologic pathways that can be targeted to prevent progression?
As the leader of the only investigator-led HF network across Asia (ASIAN-HF), Singapore is uniquely placed in this proposal to employ a “reverse translational” approach from human to animal models. Genetic, epigenetic, clinical and imaging data from ASIAN-HF patients will be used to guide “reverse translation” to rodents. This will provide novel small animal models suitable for parallel advanced imaging in SBIC and immediately applicable to pre-clinical pharmaceutical studies.
We will further develop, in parallel, a large animal model of HFpEF which is urgently needed worldwide – there is, to date, no universally accepted or validated large animal model in HFpEF, and a great industry demand for such a model. Animal models allow longitudinal assessments of disease progression across stages in HF (complementary to the cross-sectional approaches in humans, since longitudinal progression in humans would take decades to study). Target validation in animal models and eventual “feed back” to the patient cohorts in clinical trials are anticipated next steps.