Trieste, Italy – An international study, coordinated by the University of Trieste in collaboration with the Azienda Sanitaria Universitaria Giuliano Isontina and the National Amyloidosis Centre in London, may revolutionize early treatment approaches for transthyretin cardiac amyloidosis. This rare and progressive heart disease is caused by the abnormal accumulation of a protein—transthyretin—that deposits in cardiac tissues, compromising their structure and function.
The research, published in the prestigious journal JAMA Cardiology and presented at the American Heart Association (AHA) Congress, analyzed for the first time patients with transthyretin amyloid (ATTR) cardiac infiltration who had not yet developed signs or symptoms of heart failure. Using advanced imaging techniques, researchers demonstrated that patients with moderate to severe cardiac infiltration (scintigraphic grades 2 and 3) exhibited typical signs of amyloid cardiomyopathy, with evident abnormalities in echocardiography and serum biomarkers. The disease progressed more rapidly in these patients, with more than 50% developing heart failure symptoms requiring diuretic therapy within three years of diagnosis.
Aldostefano Porcari, research fellow at the University of Trieste and first author of the study, explains: “Current European and American guidelines recommend treatment with 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 halting disease progression. This finding paves the way for a possible revision of treatment guidelines, aiming to intervene before symptoms appear.”
This study represents a crucial starting point for future research on cardiac amyloidosis. The results suggest that, in the early stages of the disease, amyloid deposits may bind less rigidly to the extracellular matrix of the heart—the protein network that provides structural support to cardiac tissues. This phenomenon could make amyloid deposits more susceptible to potential treatments. With the development of new therapies targeting amyloid removal, these insights will be valuable for improving treatment effectiveness, allowing for more targeted interventions in the initial phases of the disease.
Amyloidosis refers to a group of disorders characterized by the abnormal and harmful accumulation of amyloid protein in the extracellular space. These are multisystem diseases, with the heart being one of the most commonly affected organs. The term “cardiac amyloidosis” thus refers to heart disease associated with amyloidosis. The condition primarily affects men over the age of 60, with risk factors including plasma cell disorders, chronic diseases, and genetic mutations. Current treatments involve specific medications depending on the type of amyloidosis diagnosed, aiming to eliminate or stabilize the source of the amyloidogenic protein.
Until a few years ago, cardiac amyloidosis was diagnosed only in advanced stages when the heart was already severely compromised. Today, thanks to advancements in non-invasive diagnostics, the disease can be detected early, opening new possibilities for intervention. Despite similar mortality rates among different patient groups, cardiovascular-related mortality risk in patients with scintigraphic grades 2 and 3 was found to be approximately five times higher than in those with grade 1, where deaths were more frequently due to non-cardiac causes. A key factor in this study was the use of an advanced imaging technique—bone tracer scintigraphy combined with single-photon emission computed tomography (SPECT) and computed tomography (CT)—to identify transthyretin cardiac amyloidosis in asymptomatic patients and track disease progression in this population.
The research team from the University of Trieste and the Azienda Sanitaria Universitaria Giuliano Isontina includes Aldostefano Porcari, research fellow and first author of the study; Gianfranco Sinagra, professor at the Department of Medical, Surgical, and Health Sciences of the University of Trieste and director of the Cardio-Thoracic-Vascular Department at Cattinara Hospital; and Valentina Allegro, a specialist trainee at the University of Trieste. A total of twelve leading international cardiology centers participated in the research project.
The study will continue with the involvement of additional researchers from the University of Trieste, including Rossana Bussani, professor of Pathological Anatomy and expert in histological evaluation of cardiac and extracardiac amyloid deposits, and Gabriele Stocco, associate professor of Pharmacology, who, together with Gianfranco Sinagra, has promoted the acquisition of a mass spectrometer in Trieste for advanced characterization of amyloid deposits. Through these initiatives, the University of Trieste aims to develop new diagnostic and therapeutic strategies, enabling increasingly early and targeted interventions for the management of cardiac amyloidosis.
Expert Contact
Dr. Aldostefano Porcari PhD
Email aldostefano.porcari@asugi.sanita.fvg.it