Navigating the emerging landscape of asymptomatic ATTR-CM: challenges, opportunities and the path ahead

Sep 28, 2026

Uploaded by SANS

Transthyretin amyloid cardiomyopathy (ATTR-CM) has been regarded as rare and relentlessly fatal; advances in noninvasive diagnosis, increased disease awareness, and available treatments now allow identification during asymptomatic stages, before overt heart failure (HF). This emerging population creates challenges and opportunities for improving care, yet data remain limited because asymptomatic patients were excluded from clinical trials and management relies on empirical judgment. Understanding natural history supports individualized clinical decisions and informs future trial design.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Abstract

Plain Language Summary

Introduction

Evolution of ATTR-CM and diagnosis in asymptomatic stages

Article History and Keywords

FUTURE CARDIOLOGY 2025, VOL. 21, NO. 12, 1155–1164 [https://doi.org/10.1080/14796678.2025.2591554](https://doi.org/10.1080/14796678.2025.2591554) | REVIEW

Navigating the emerging landscape of asymptomatic ATTR-CM: challenges, opportunities and the path ahead
Aldostefano Porcari a,b,c
aNational Amyloidosis Centre, Division of Medicine, University College London, Royal Free Hospital, London, UK; bCenter for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), University of Trieste, Trieste, Italy; cEuropean Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart-ERN GUARD-Heart, Trieste, Italy | | | | --- | --- | --- | | ABSTRACT
Transthyretin amyloid cardiomyopathy (ATTR-CM) has long been considered a rare and inexorably fatal condition. However, advances in noninvasive diagnosis, disease awareness, and available treatments have enabled diagnosis in asymptomatic stages, before development of clinical heart failure (HF) . The emerging entity of asymptomatic ATTR-CM presents both challenges and new opportunities for improving patient care. Data remain limited, as asymptomatic patients have been excluded from clinical trials, and their management currently relies on empirical judgment. Understanding the natural history of asymptomatic ATTR-CM is essential for guiding individualized clinical decisions at the patient level and for designing future clinical trials in this population. While these patients do not exhibit overt HF, recent evidence suggests that a subset may experience disease progression and develop significant morbidity and mortality within a relatively short time. This review explores the rapidly evolving landscape of asymptomatic ATTR-CM with regard to diagnostic pathways, phenotypic variability, natural history, and prognostic stratification. It also discusses current barriers encountered in clinical practice for timely diagnosis, the clinical role of imaging and biomarkers, and potential indications for early therapeutic interventions in this under-recognized population, which is projected to exponentially increase in the coming years.
PLAIN LANGUAGE SUMMARY
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a heart disease caused by the buildup of an abnormal protein called transthyretin (TTR) in the heart muscle. This buildup makes the heart stiffer and less able to pump blood properly. In the past, most people were diagnosed only when the disease was advanced and they already had symptoms of heart failure, such as shortness of breath or swelling in the legs. Nowadays, thanks to better awareness and advances in cardiovascular imaging, ATTR-CM can be diagnosed earlier, even before symptoms appear. Some people with early signs of the disease may still face worsening of their cardiovascular condition over time. This raises important questions about how best to monitor these patients and when to begin treatment. Starting therapy early could help delay or even prevent heart failure and improve long-term outcomes | | ARTICLE HISTORY
Received 28 July 2025 Accepted 14 November 2025
KEYWORDS
Transthyretin; cardiac amyloid infiltration; asymptomatic disease; natural history; monitoring disease progression; prognosis | | 1. Introduction
Transthyretin (TTR) amyloidosis, also called ATTR amyloidosis, is a life-threatening and often underrecognized disease caused by progressive deposition of misfolded or cleaved TTR protein in various organs [1]. The more common non-hereditary form, wildtype ATTR (ATTRwt), arises from age-related impairment of homeostatic mechanisms, whereas the hereditary form, variant ATTR (ATTRv), results from destabilizing mutations in the TTR gene and may present in younger individuals [2]. Amyloid fibril aggregation within the extracellular matrix disrupts tissue structure, integrity, and function, ultimately leading to organ dysfunction [3]. In clinical practice, A

FAQs

Why is asymptomatic ATTR-CM challenging to manage clinically?

Asymptomatic patients were excluded from disease-modifying treatment trials, so management currently depends on clinical judgment and empirical practice despite limited data.

What enables earlier diagnosis of ATTR-CM before heart failure symptoms appear?

Better awareness and advances in cardiovascular imaging support noninvasive diagnostic pathways that can detect ATTR-CM in earlier, symptom-free stages.

How does the review describe the natural history of asymptomatic ATTR-CM?

While these patients do not show overt HF, evidence suggests some may experience disease progression and develop morbidity and mortality within a relatively short time, making prognostic stratification important.

Sep 28, 2026

Uploaded by SANS