Roughly one in three Americans is at risk for heart failure1, a condition where the heart can no longer effectively pump blood. And one in four will develop heart failure at some point in their lives1. Behind these statistics is a complex issue: the causes of heart failure differ widely among affected individuals. And identifying the underlying cause – especially if it’s rare – can be tricky.

Among the less recognized causes is transthyretin amyloid cardiomyopathy, or ATTR-CM, which can mimic classic heart failure. Early suspicion and diagnosis are crucial: the longer ATTR-CM goes unnoticed, the greater the risk of irreversible heart damage and loss of quality of life. That’s why Pfizer is working with other industry partners as part of the ASPIRE group, led by Amyloidosis Research Consortium (ARC), to accelerate a new era of suspicion and recognition—driven by artificial intelligence (AI) and collective expertise.

What is ATTR-CM and How is it Related to Heart Failure?

ATTR-CM is thought to affect up to 150,000 Americans.2 The condition arises when transthyretin, a naturally occurring protein in the body, becomes unstable and breaks apart. Fragments of this protein then misfold into amyloid fibrils and build-up in the heart muscle, causing it to become stiff and making it harder to pump blood, eventually leading to heart failure. These amyloid fibrils can also build up in other parts of the body, leading to seemingly unrelated symptoms like carpal tunnel syndrome and lower back pain (spinal stenosis).

“There’s no single ‘classical presentation’ for ATTR-CM, aside from the buildup of amyloid fibrils in the heart,” says Nisith Kumar, Director of Global Medical Affairs in TTR Amyloidosis at Pfizer. “As a result, symptoms can appear unrelated to each other: For example, symptoms of carpal tunnel that develop years before cardiac symptoms, like shortness of breath. It’s very difficult to identify these early symptoms as ‘red flags’ for the disease.”

Bringing Earlier Diagnosis within Reach

These early ‘red flags’ had traditionally complicated diagnosis, but they also presented an opportunity. What if doctors could identify opportunities to explore testing for ATTR-CM earlier — potentially, before patients developed more serious cardiac symptoms?

Turning that vision into reality would be daunting. Researchers would need to analyze anonymized data collected from hundreds of thousands of patients, scouring millions upon millions of data points to find patterns that could help physicians identify the many potential presentations of ATTR-CM.

But Pfizer had a vision that would make it work. “We knew that such a large undertaking would require input from multiple stakeholders across the industry,” says Kumar. “We all wanted to put patients first — and we set out to create a pre-competitive space that would allow us to collaborate and share our findings.”

That vision evolved into the Amyloidosis Stakeholder Partnership for Impact, Reach & Equity (ASPIRE) project, led by ARC. ASPIRE, co-chaired by Kumar, is a partnership between 10 industry stakeholders, including Pfizer, to fund independent research into amyloidosis, including ATTR-CM. The project is organized into three working groups comprising coordinated care, diagnostic pathways, and health equity. ASPIRE’s mission is to address health disparities and accelerate progress in diagnosis and care.

Harnessing Artificial Intelligence: The ASPIRE Approach

The ASPIRE diagnostic pathways working group is exploring how AI could help doctors spot red flags in ATTR-CM sooner. To do this, they conducted a comprehensive literature review3, brought together experts and released a white paper that laid out both opportunities and limitations of AI in this space.

The AI tools they discussed incorporate a variety of clinical features: unexplained thickening of the heart wall, abnormal electrocardiograms, subtle changes in heart imaging, and even clues from patient histories.

However, having approved AI tools available doesn’t guarantee their use in clinical practice. These tools need to be tested in real-life medical settings, so healthcare teams can figure out how best to include them in their daily work.

“AI excels at finding diffuse patterns that can be near-impossible for the human brain to detect,” explains Lori Baylor, a Senior Medical Director of Rare Cardiology at Pfizer and ​​the co-lead for the ASPIRE AI project. “It can never replace the expertise or care of a doctor, but it can be the flashlight that helps doctors figure out where to look as they work toward a diagnosis.”

For patients and their families, this type of innovation means hope and relief from the uncertainty that accompanies undiagnosed illness.

As reported in the ASPIRE AI white paper, patients expressed that it comes down to one thing: “I'd rather be scared about nothing than oblivious to something” and “Yes, I want the results of any data used to scan my records — then we can figure out if it is accurate. It is also stressful not knowing.”

Collective Brilliance: A Blueprint for the Future

The collaborative nature of the ASPIRE project represents a new approach to patient-centric research — one that could become the blueprint to help patients living with other forms of amyloidosis, or even other more common diseases.

“The individuals involved in ASPIRE all come from different backgrounds. We have different training, and we all have different experiences. And when we rally together for the betterment of patient care, we’re able to create more than we ever could have otherwise,” says Baylor.

Pre-competitive initiatives like ASPIRE allow organizations to pool expertise, accelerate research, and address challenges that are too complex for any one company to solve alone. By focusing on shared goals—such as expediting suspicion and recognition of ATTR-CM—participants can create impact at scale, ultimately benefiting patients and public health.

The journey toward faster recognition of ATTR-CM is far from over. As AI tools mature and collaborative networks expand, we are poised to unlock new possibilities with the single goal of improving the outlook for patients.

Learn more about Pfizer’s work in AI: Harnessing the Power of AI to Detect ATTR-CM