In memoriam: Claudio Rapezzi

Abstract

Claudio Rapezzi passed away at the age of 71, leaving abruptly all his patients, friends, colleagues, and pupils. Rapezzi ‘was first and foremost a clinician who always put the patient first and could always be counted on to appropriately frame new discoveries’, as Frederick Ruberg wrote. He gave a substantial contribution to the advance in medical knowledge thanks to his unique qualities of curiosity, culture, and imaginative vision in each of the many fields his work touched: from the never-ending love for electrocardiography, manifested from his first publication1 up to its novel applications in cardiomyopathies, to the legacy he has left in cardiac amyloidosis with the ‘many ideas that we take for granted now, bone tracer cardiac imaging, tafamidis and so much more’, as Sharmila Dorbala has written, to the last Editorial on sex differences in this disease.2 Amyloid transthyretin cardiomyopathy (ATTR-CM) is emerging as an important cause of morbidity and mortality and a widely underdiagnosed disorder. One of the reasons for the recent interest on ATTR-CM is the availability of an algorithm for the non-invasive diagnosis of this condition. Indeed, the combination of an intense cardiac uptake of bone tracers and the absence of a monoclonal protein allows us to diagnose ATTR-CM without the need for the demonstration of amyloid deposits on tissue samples from the heart or an extracardiac site.1 In detail, cardiac uptake must be as intense as that of the sternum and ribs (Perugini Grade 2), or more intense than the sternum and ribs (Perugini Grade 3).3 The Perugini grading system is named after Enrica Perugini, the first author of a seminal paper published in 2005 by the research group from Bologna coordinated by Claudio Rapezzi.3 It was thus Prof. Rapezzi who introduced this very simple grading system and understood its relevance for the differential diagnosis between light-chain and ATTR-CM. Indeed, an international collaboration led by Rapezzi and the group of the National Amyloidosis Centre in London established in 2016 that ‘the combined findings of grade 2 or 3 myocardial radiotracer uptake on bone scintigraphy and the absence of a monoclonal protein in serum or urine had a specificity and positive predictive value for cardiac ATTR amyloidosis of 100%’,4 thus introducing the concept of a non-invasive diagnosis of ATTR-CM that is now adopted worldwide.5 Every diagnosis of ATTR-CM made without the need of a tissue biopsy is then an ideal tribute to the vision of Rapezzi. In the same years, the Phase 3 Safety and Efficacy of Tafamidis in Patients with Transthyretin Cardiomyopathy (ATTR-ACT) trial was evaluating the TTR stabilizer tafamidis in patients with ATTR-CM. The results of this trial, presented by Rapezzi during the 2018 European Society of Cardiology meeting in Munich, opened a new therapeutic avenue for patients with ATTR-CM from all over the world.6 Tafamidis still remains the only approved treatment for ATTR-CM, either variant or wild-type, with a demonstrated survival benefit confirmed even in a long-term extension study.7 Rapezzi also contributed greatly to spread the knowledge on ATTR-CM through multiple initiatives, ranging from a position statement of the European Society of Cardiology on the diagnosis and management of amyloid CM8 to other consensus documents,9–12 to talks and educational activities in many congresses, and the formation of many young clinicians and fellows, many of whom established new outpatient clinics devoted to amyloid CM.