An international study, co-ordinated by the University of Trieste, in collaboration with the local health services (Azienda Sanitaria Universitaria Giuliano Isontina – ASUGI), and the National Amyloidosis Centre in London, may revolutionise the prospects for early treatment of transthyretin cardiac amyloidosis (ATTR-CA), a rare and progressive heart disease caused by the abnormal accumulation of a protein – transthyretin – that is deposited in cardiac tissue, compromising its structure and function.

The study, published in the prestigious journal JAMA Cardiology and presented at the American Heart Association (AHA) Congress, analysed for the first time patients with transthyretin (ATTR) cardiac amyloid infiltration who had not yet developed signs or symptoms of heart failure. Using an advanced imaging technique, the researchers demonstrated that patients with moderate to severe cardiac infiltration (scintigraphic grades 2 and 3) already exhibited typical features of amyloid cardiomyopathy, with abnormalities visible on both echocardiogram and serum biomarkers. In these patients, the disease progressed more rapidly, with over 50% developing signs and symptoms of heart failure requiring diuretic therapy within three years of diagnosis.

Aldostefano Porcari, research assistant at the University of Trieste and first author of the publication, explains: ‘Current European and American guidelines recommend treatment with the drug tafamidis only for patients who have already developed overt heart failure. However, our study suggests that even asymptomatic patients with advanced cardiac infiltration could benefit from early treatment, potentially slowing or even halting disease progression. These findings pave the way for a possible revision of therapeutic recommendations, with the aim of intervening before the onset of symptoms.’

This study represents a key starting point for future research into cardiac amyloidosis. The findings suggest that, in the early stages of the disease, amyloid deposits may bind less tightly to the heart’s extracellular matrix — the network of proteins that provides structural support to cardiac tissue. This phenomenon could make amyloid deposits more susceptible to potential treatments. As new therapies are developed to target amyloid removal, these insights will be crucial for improving treatment effectiveness, enabling more targeted intervention in the early phases of the disease.

THE DISEASE

The term amyloidosis refers to a group of disorders characterised by the abnormal and harmful accumulation of amyloid protein in the extracellular space. Amyloidoses are multisystem diseases, and one of the organs most commonly affected is the heart. The term ‘cardiac amyloidosis’ refers specifically to heart conditions associated with amyloidosis. These diseases primarily affect men over the age of 60. Risk factors include plasma cell disorders, chronic illnesses, and genetic mutations. Currently, treatment involves specific medications depending on the type of amyloidosis diagnosed, with the aim of eliminating or stabilising the source of the amyloid-forming protein.

Until a few years ago, this condition was typically diagnosed only at an advanced stage, when the heart was already severely compromised. Today, thanks to advances in non-invasive diagnostics, it is possible to detect the disease at an earlier stage, opening up new possibilities for intervention. Although overall mortality rates were similar across patient groups, the risk of death from cardiovascular causes in patients with grade 2 and 3 cardiac infiltration was found to be approximately five times higher than in those with grade 1, where deaths were more often attributed to non-cardiac causes.

A key role was played by the use of an advanced imaging technique – bone tracer scintigraphy combined with single-photon emission computed tomography (SPECT) and computed tomography (CT) – to identify ATTR cardiac amyloidosis in asymptomatic patients and to study disease progression in this population.

THE TEAM

The study was led by a team from the University of Trieste and ASUGI, including Aldostefano Porcari, research assistant and first author of the publication; Gianfranco Sinagra, professor in the Department of Medical, Surgical and Health Sciences at the University of Trieste and Head of the Cardio-Thoraco-Vascular Department at Cattinara Hospital; and Valentina Allegro, a medical resident at the University of Trieste.

The research project involved a total of twelve leading international cardiology centres.

Dr. Porcari was invited to present the study’s findings in the prestigious ‘Samuel A. Levine Early Career Clinical Investigator Award’ session, an honour reserved for young researchers who have made significant contributions to clinical cardiology.

Research in this field will continue at the University of Trieste with the involvement of Rossana Bussani, Professor of Pathological Anatomy and expert in the histological assessment of cardiac and extracardiac amyloid deposits, and Gabriele Stocco, Associate Professor of Pharmacology. Together with Gianfranco Sinagra, Professor Stocco promoted the acquisition of a mass spectrometer in Trieste for the advanced characterisation of amyloid deposits. Through these initiatives, the University of Trieste aims to develop new diagnostic and therapeutic strategies, with the goal of enabling earlier and more targeted interventions in the management of cardiac amyloidosis.

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Full study published in Jama Cardiology

Clinical Phenotype and Prognosis of Asymptomatic Patients With Transthyretin Cardiac Amyloid Infiltration

Aldostefano Porcari, MD1,2,3; Yousuf Razvi, MBChB, BSc1; Francesco Cappelli, MD, PhD4,5; et al

1. National Amyloidosis Centre, Division of Medicine, University College London, Royal Free Hospital, London, United Kingdom
2. Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina, University of Trieste, Trieste, Italy
3. European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart, ERN GUARD-Heart, Trieste, Italy
4. Cardiomyopathy Unit, Careggi University Hospital, University of Florence, Florence, Italy
5. Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy