The Rising Tide of Heart Failure in Singapore and Asia

Heart failure remains a pressing public health challenge in Singapore, accounting for 17 percent of all cardiac admissions and contributing to an average of 23 daily deaths from heart disease. With an aging population and rising rates of comorbidities like diabetes, obesity, and hypertension, the prevalence is projected to surge, particularly among Southeast Asians who often develop the condition a decade earlier than Western populations. Heart failure with preserved ejection fraction (HFpEF), where the heart muscle stiffens but maintains normal pumping strength, represents about 50 percent of cases and poses unique difficulties due to limited effective treatments.

This regional burden underscores the urgency for innovative research, positioning Singapore's biomedical ecosystem—anchored by institutions like Duke-NUS Medical School and the National University of Singapore (NUS)—at the forefront of developing tailored solutions.

Understanding HFpEF: Why Asian Patients Need Specialized Models

HFpEF features diastolic dysfunction, fibrosis, and hypertrophy, leading to inadequate filling during relaxation. In Asia, patients present younger, with higher rates linked to metabolic factors. Traditional animal models fail to replicate these human-specific traits, resulting in high drug failure rates in trials. Singapore researchers are addressing this gap by engineering patient-derived models that mirror Asian physiology.

Dr. Chrishan Ramachandra from the National Heart Centre Singapore (NHCS), affiliated with Duke-NUS, emphasizes that individual responses to medications vary widely, making personalized testing essential for optimizing therapies.

The Heart-in-a-Jar Technology: A Step-by-Step Breakdown

The 'Human Heart-in-a-Jar' is a fingertip-sized, 3D bioengineered ventricular cardiac organoid chamber (hvCOC) that beats and pumps like a real heart. Here's how it's created:

• Step 1: Collect 5ml blood from HFpEF patients via NHCS Biobank.
• Step 2: Reprogram blood cells into induced pluripotent stem cells (iPSCs) using Yamanaka factors.
• Step 3: Differentiate iPSCs into ventricular cardiomyocytes (hvCMs) with proprietary protocols.
• Step 4: Embed hvCMs in collagen hydrogel within a custom mold.
• Step 5: Culture in bioreactor; cells compact gel, forming a hollow chamber that generates pressure.

This model measures contractility, electrophysiology, and arrhythmias accurately, outperforming 2D cultures or animals.

NHCS and Novoheart Collaboration: Pioneering Asia's First Model

Launched in November 2023, the NHCS-Novoheart (Medera subsidiary) partnership received S$5 million from A*STAR's Industry Alignment Fund. NHCS supplies patient cells; Novoheart provides automation for high-throughput screening. The goal: Asia-specific HFpEF models for precision drug testing, aligning with FDA Modernization Act 2.0.Learn more from NHCS announcement.

Prof. Derek Hausenloy, NHRIS Director, highlights its potential for new discoveries in Asian HF mechanisms.

Recent Milestones: From Modeling to Clinical Trials

By 2024, the mini-heart platform optimized doses for Sardocor's SRD-001 gene therapy (NCT04703842), launching Asia's first multi-centre HFrEF trial at NHCS, NUHCS, and TTSH. At ISSCR 2025, Novoheart showcased superior prediction of human outcomes, supporting FDA Fast Tracks. In November 2025, Agilent partnered NHCS for metabolic profiling of organoids using Seahorse analyzers, targeting diabetic HF.

Singapore's Higher Education Ecosystem Driving Innovation

Duke-NUS leads with stem cell therapies for HF regeneration and fibrosis genes like WWP2. NUS Yong Loo Lin School advances iPSC heart cells; NTU's Lee Kong Chian School explores organ-on-chip. A*STAR's Singheart molecule promotes self-healing cardiomyocytes. These efforts converge at NHCS, fostering clinician-scientist training.

Collaborative platforms like PREVENT-HF validate organoid findings clinically.

Stakeholder Perspectives: From Bench to Bedside

Dr. Ronald Li, Medera CEO, stresses cross-sector translation for patient benefits. NHCS treats 3000 HF patients yearly, integrating research into LVADs, transplants. Industry partners like AstraZeneca previously used Novoheart for HFpEF models leading to trials.

Implications for Personalized Medicine and Drug Development

These models enable high-throughput screening, reducing costs and failures. Patient-specific testing predicts responses, accelerating therapies. For Singapore, it bolsters biotech hub status, creating jobs in stem cell research.EurekAlert on partnership.

Challenges: Scalability, Ethics, and Validation

• Maturing organoids to adult-like function.
• Ethical iPSC sourcing and standardization.
• Regulatory alignment for FDA/EMA.

Ongoing trials validate predictive power.

Future Outlook: Towards Regenerative Therapies

By 2030, expect routine organoid use in trials, gene edits for HF reversal. Singapore's investments position universities to lead, training next-gen researchers.

Actionable Insights for Researchers and Students

• Pursue iPSC training at Duke-NUS/NUS.
• Collaborate via A*STAR grants.
• Explore organoid roles in precision cardio.

This breakthrough exemplifies Singapore higher ed's impact on global health.

Photo by Rayson Tan on Unsplash