We need to talk about the zebra in the room: ATTR-CM and the patients we’re missing

In medicine, there’s a principle: ‘when you hear hoofbeats, think horses, not zebras’

For patients with less obvious conditions like transthyretin amyloid cardiomyopathy (ATTR-CM), that principle can come at a cost. ATTR-CM is often described as ‘rare’, but more accurately, it is rarely diagnosed.

Earlier this year, we reflected on what it means to live with a rare disease, from delayed diagnosis to fragmented care and the growing importance of patient-centred innovation. Today, as part of our rare disease spotlight series, we shine a light on ATTR-CM, a condition that exemplifies both the progress being made in rare disease science and the persistent gaps in patient experience.

A condition hiding in plain sight

ATTR-CM is a progressive and potentially fatal disease caused by the misfolding of transthyretin, a protein that accumulates in the heart, nerves and other organs. Over time, this buildup can stiffen the heart muscle, leading to heart failure and a range of debilitating symptoms.1 Yet one of the defining features of ATTR-CM is how easily it can be overshadowed by more familiar conditions, particularly if you aren’t expecting it.

Symptoms such as shortness of breath, fatigue and swelling in the lower legs closely resemble more common cardiovascular conditions. As a result, patients are often treated for heart failure, hypertension or other diagnoses before ATTR-CM is even considered.1 Emerging real-world evidence also suggests its links with other seemingly unrelated conditions, such as carpal tunnel syndrome, which may precede cardiac symptoms by years,2 further contributing to prolonged and complex diagnostic journeys.

The cost of delay

Patients frequently move between specialities, undergoing repeated tests and consultations before they receive an accurate diagnosis. During this time, symptoms may worsen, quality of life declines and uncertainty is compounded with each referral, each test and each inconclusive result.

Patient advocacy groups highlight that this experience is often marked by anxiety, frustration and a lack of clear, accessible information. In a conversation we had with Amyloidosis UK, this came through strongly – patients and their families want reliable, detailed information early in their journey, yet too often it is unavailable at the point when it is most needed.

A diagnosis of ATTR-CM can fundamentally reshape a person’s life, affecting their ability to work, financial stability and independence. In the UK, access to specialist amyloidosis centres is limited, with care concentrated in London and Birmingham as of April 2026. For patients – most of whom are diagnosed at around 65 – and their caregivers living outside of these areas, these journeys are not just inconvenient, they can be physically exhausting and overwhelming. Over time, people end up navigating more than just the condition – they’re navigating the gaps between specialities, services and clinical pathways without a clear sense of what should happen next.

Innovation is advancing but gaps remain

Disease-modifying therapies have changed the treatment landscape, helping to stabilise the transthyretin protein and improve outcomes.3 More recently, new approaches are expanding the range of options available to patients, including gene-silencing therapies and next-generation stabilisers.4,5 The pipeline continues to evolve, with research exploring RNA-based therapies, amyloid-clearing strategies and even gene-editing technologies that could transform long-term disease management.6,7

Innovation is changing what’s possible, but it’s not yet changing who gets to benefit from it. Critically, only a fraction of patients are ever diagnosed in the first place. And of those who are, real-world data shows that many continue to experience disease progression, hospitalisations and unmet needs despite treatment.8 Without earlier recognition, clearer pathways and equitable access to care, the benefits of scientific progress risk reaching only a subset of those who need them.

Moving forward

ATTR-CM highlights a broader challenge across rare diseases: the gap between what is scientifically possible and what patients experience in the real world. If patients are to benefit from advances in treatment, earlier identification of ‘red flag’ symptoms needs to become part of routine care. Clear, patient-appropriate information that empowers understanding and decision making is also critical – equipped in this way, patients can participate more meaningfully in decisions about their care. Equally important is recognising the role of caregivers and wider support networks, particularly in conditions that predominantly affect older populations.

Organisations like Amyloidosis UK are already working to address these gaps; advocating for clearer care pathways, improved access to treatment, and better quality, patient-appropriate information. Their efforts reinforce the reality that more work is needed to ensure patients can meaningfully participate in decisions about their care. ATTR-CM may be classified as a rare disease, but the challenges it represents – delayed recognition, fragmented care and unequal access – are far more common.

As part of the Patient and Customer Experience team at Inizio Engage XD, we champion ‘Shared Health’ by ensuring both patients and healthcare professionals are reflected in the content and campaigns we create. By combining therapy area expertise with empathy and creativity, we aim to equip rare disease patients and HCPs with the information they need to forge human connections, make shared decisions and achieve healthier outcomes together.

Sources:

1. American Heart Association. Transthyretin amyloid cardiomyopathy (ATTR-CM). 2024. https://www.heart.org/en/health-topics/cardiomyopathy/what-is-cardiomyopathy-in-adults/transthyretin-amyloid-cardiomyopathy-attr-cm
2. Razvi Y, et al. JACC Heart Fail 2026;14(4):102890
3. National Institute for Health and Care Excellence. Technology appraisal guidance [TA984]. 2024. https://www.nice.org.uk/guidance/ta984
4. National Institute for Health and Care Excellence. Technology appraisal guidance [TA1115]. 2025 https://www.nice.org.uk/guidance/ta1115
5. National Institute for Health and Care Excellence. Technology appraisal guidance [TA1121]. 2025. https://www.nice.org.uk/guidance/ta1121
6. Ang SP, et al. Heart Fail Rev 2025;30(4):759-770
7. Amyloidosis Research Consortium. ATTR amyloidosis clinical trials (January 2026). 2026. https://arci.org/resource/attr-amyloidosis-clinical-trials/
8. Fontana M, et al. J Card Fail 2025;31(1):318