Research Themes
GOALS
Through our clinical trials and research, we seek to understand how better to detect and treat heart disease, especially among the population in Singapore and more widely, Asia. Our studies aim to determine the driver causes of heart disease and disease susceptibility. Additionally, we seek to discover new ways of detecting early heart disease, novel methods to prevent disease onset and progression, as well as new treatments and monitoring tools for heart disease in a Singaporean context.
Sub-Themes
Evidence from our studies suggests that metabolic dysfunction is a major driver of cardiovascular disease in Singapore. Lipid, immune and metabolic factors associate with early heart disease, linking fatty liver together with quantifiable lifestyle factors.
Our proposed studies in cardiometabolic disease seek to combine cardiovascular and metabolic assessment of patients, together with liver fat assessment, brain imaging and cognition assessment, with and without diabetes, converging multiple imaging and non-imaging clinical and molecular biomarkers, to map out the full range of normal to abnormal cardiovascular-metabolic function and systems-wide associations.
Ischaemic heart disease is the leading cause of mortality globally, responsible for around 9 million deaths in 2019. Acute myocardial infarction (AMI), commonly known as heart attack, accounts for most of these fatalities. In Singapore alone, there were approximately 11,000 cases of heart attacks reported in 2020. While advances in medical therapy and percutaneous coronary intervention have reduced mortality rates, heart failure (HF) occurring after MI has become a major cause of morbidity and mortality among survivors. Approximately 4.5% of Singapore’s population lives with HF, imposing a considerable financial burden on individuals, healthcare systems, and society.
Under CVMD-TRP, we conduct clinical studies that investigate molecular mechanisms, disease biomarkers, therapeutic targets and interventions, cardiovascular risks, genetics, lifestyle differences, and treatment adherence to improve clinical outcomes for MI and HF patients. Over the years, we have curated well-annotated clinical cohorts and biobanks that support ongoing and future research. Some examples include the HF cohorts recruited in Singapore (SHOP and ATTRaCT) and New Zealand (PEOPLE) by Mark Richards; a cohort of coronary artery disease (CAD) patients from Singapore (IMMACULATE by Mark Chan) and from New Zealand (CDCS by Mark Richards). These cohorts have supported multiple studies to investigate diagnostic and prognostic protein and microRNA biomarkers, imaging studies of cardiac structure and function, molecular studies into disease mechanisms, and the search for novel therapeutic targets and interventions.
Clinical trials of therapeutic interventions include PASSIVATE, an investigator-initiated multi-centre trial funded by AstraZeneca. The trial aims to determine whether AZD5718 can reduce the progression of non-calcified coronary plaque volume. We also seek to promote technology-enabled health services research. For example, our ongoing studies aim to leverage machine learning of ECG and echocardiograms to improve risk stratification in AMI; to create a simple sensor film attached to the back of medication blister packs to monitor medication adherence (SMARTFILM-2); and use smartphones and wearables for remote health monitoring and telehealth solutions to improve health outcomes of recovering AMI patients (AMI-HOPE).
Ongoing clinical studies in CVMD-TRP seek to understand the molecular mechanisms underlying diseases such as CAD and HF, identify new biomarkers, discover novel therapeutic interventions, and leverage technology to improve the management of these chronic conditions. In the face of significant health challenges posed by these diseases, we remain committed to achieving better health outcomes for our community.
Based in the National University Health System of Singapore, the Cardiosleep research team aims to improve cardiovascular health by understanding the relationships between sleep and the heart. Since 2009, our works have been published in top-tier medical journals and presented at eminent scientific meetings.
Obstructive sleep apnoea is a prevalent condition characterized by recurrent episodes of upper airway obstruction by soft tissue and tongue during sleep. Patients typically present with snoring, disrupted sleep and excessive daytime sleepiness. These lead to blood pressure elevation, stroke and various forms of heart disease such as myocardial infarction (heart attack), atrial fibrillation (irregular heartbeats) and heart failure.
As the symptoms of obstructive sleep apnoea are non-specific, many patients are not aware of the condition until a much later stage. The prolonged insults from untreated obstructive sleep apnoea contribute to the occurrence of heart disease. Our team has shown that heart disease patients with concomitant obstructive sleep apnoea have worse outcomes than those without.
We believe that all our patients deserve the highest level of care. Through our research, we are committed to identifying new knowledge to improve clinical care for our patients.
The CVMD-TRP is at the forefront of collaborative research initiatives that push the boundaries of advanced imaging techniques within a clinical framework. Our access to cutting-edge equipment, such as echocardiography, cardiovascular magnetic resonance, and cardiovascular computed tomography scanners at the National University Hospital, enables us to conduct investigations in both the inpatient and outpatient settings. Furthermore, our close collaboration with the Clinical Imaging Research Centre at the National University of Singapore provides invaluable insights through dedicated research scanners for hybrid PET-CT and hybrid PET-MR. Additionally, our partnership with the Centre for Translational Magnetic Resonance at the National University of Singapore grants us access to state-of-the-art 3T MRI scanners.
Through our interdisciplinary approach, we explore the interconnected domains of cardiac, neurological, hepatic, and metabolic research. To enhance our image analysis capabilities, we employ sophisticated in-house post-processing tools and continually expand our repertoire to include artificial intelligence and machine learning in our work. Moreover, our international collaborations with esteemed researchers have resulted in the publication of multi-centre studies in influential journals.
The Cardiovascular Research Institute, led by Prof Roger Foo, has developed deep expertise in bleeding age cardiovascular imaging and biomarker capabilities over the past decade. These capabilities interface with the National University Heart Centre Clinical Trials Unit and Platform 2 of the Cardiovascular DiseasE National Collaborative Enterprise (CADENCE; https://www.cris.sg/our-programmes/cadence/), both led by Dr. Lim Shir Lynn. During the recent SARS-CoV-2 pandemic, A/Prof Mark Chan led the trial “The IMproving reModeling in Acute myoCardial Infarction Using Live and Asynchronous TElemedicine (IMMACULATE)”. This multicentre trial, published in JAMA Cardiology (https://jamanetwork.com/journals/jamacardiology/fullarticle/2774447), randomised 301 patients with acute myocardial infarction to remote post-discharge care led by nurse clinicians and in-person care led by cardiologists. In the remote nurse clinician-led arm, patients were monitored and consulted with via telemedicine by cardiovascular nurse clinicians who titrated their medications including renin-angiotensin system inhibitors and beta-blockers. Although the trial did not meet its primary endpoint of better cardiac magnetic resonance imaging-measured left ventricular remodelling compared with standard in-person cardiologist-led care or its secondary endpoint of greater NT-pro-BNP reduction in the nurse clinician-led arm, an on-treatment analysis showed better uptitration of renin angiotensin system inhibitors in the nurse clinician led arm and lower left ventricular mass index in this arm. The trial also showed that nurse clinician-led remote care was as safe as cardiologist-led in-person care, with numerically fewer serious adverse events in the nurse clinician-led arm (https://clinicaltrials.gov/study/NCT02468349). A/Prof Mark Chan is also the lead PI of the PASSIvation of Vulnerable Plaque with AZD5718 in AcuTe Coronary syndromE (PASSIVATE) trial. This randomized multicentre international trial randomised 210 patients with AMI in an investigator-initiated externally-sponsored trial of a novel anti-inflammatory investigational medical product with 1.75M SGD funding from NMRC and 11.1M USD in-cash funding from Astra-Zeneca (https://clinicaltrials.gov/study/NCT04601467). The trial leverages quantitative coronary plaque volume imaging and pericoronary adipose tissue quantification in addition to proteomic and lipidomic endpoints in determining the efficacy of the anti-inflammatory compound, AZD5718, in improving coronary arterial health among patients with acute coronary artery disease compared with placebo. A/Prof Mark Chan is also the co-director of CArdiovascular DiseasE National Collaborative Enterprise (CADENCE) https://www.cris.sg/our-programmes/cadence/.