RESUMO
AIMS: Hereditary Transthyretin Amyloidosis (ATTRv) is one of the leading etiologies of systemic amyloidosis with more than 135 mutations described and a broad spectrum of clinical manifestations. We aimed to provide a systematic description of a population of individuals carrying pathogenic mutations of transthyretin (TTR) gene and to investigate the major clinical events during follow up. METHODS: Observational, retrospective, cohort study including consecutive patients with mutations of TTR gene, admitted to a tertiary referral center in Bologna, Italy, between 1984 and 2022. RESULTS: Three hundred twenty-five patients were included: 106 asymptomatic carriers, 49 cardiac phenotype, 49 neurological phenotype and 121 mixed phenotype. Twenty-two different mutations were found, with Ile68Leu (41.8%), Val30Met (19%), and Glu89Gln (10%) being the most common. After a median follow-up of 51 months 111 patients (38.3%) died and nine (11.5%) of the 78 asymptomatic carriers developed ATTRv. Carriers had a prognosis comparable to healthy population, while no significant differences were seen among the three phenotypes adjusted by age. Age at diagnosis, NYHA class III, LVEF, mPND score IV and disease-modifying therapy were independently associated with survival. CONCLUSIONS: This study offers a wide and comprehensive overview of ATTRv from the point of view of a tertiary referral center in Italy. Three main phenotypes can be identified (cardiac, neurological and mixed) with specific clinical and instrumental features. Family screening programs are essential to identify paucisymptomatic affected patients or unaffected carriers of the mutation, to be followed through the years. Lastly, disease-modifying therapy represents an evolving cornerstone of the management of ATTRv, with a great impact on mortality.
A total of 325 consecutive patients harboring a pathogenic mutation in the TTR gene, admitted to a tertiary referral center in Bologna, Italy, between 1984 and 2022 were included in the study. These patients exhibited significant clinical diversity: 106 were asymptomatic carriers, 49 presented with a cardiac phenotype, 49 with a neurological phenotype, and 121 had a mixed phenotype. Asymptomatic carriers demonstrated a prognosis comparable to healthy population but some of them may develop signs and symptoms of the disease during follow-up. Survival curves adjusted by age are similar among the three phenotypes. Age at diagnosis, NYHA class, mPND score, left ventricular ejection fraction and disease-modifying therapy were identified as independent factors associated with prognosis.
RESUMO
Cancer therapy-induced cardiotoxicity is an emerging clinical and healthcare issue. Myocardial dysfunction and heart failure are mostly responsible for increased cardiovascular mortality in cancer disease survivors. Several imaging surveillance techniques have been proposed for early diagnosis of cancer therapy-induced cardiac dysfunction. Our aim was to provide an update of radionuclide angiography applications in this field. Radionuclide angiography is widely used to assess left ventricular ejection fraction (LVEF) throughout cancer treatment, especially in patients with limited acoustic window. Additional prognostic data may be provided by phase analysis and diastolic function evaluation. Low LVEF and high approximate entropy at baseline seem to be predictors for cancer therapy-induced cardiac dysfunction. A decrease in peak filling rate and/or an increase in time to peak filling rate may be observed in patients undergoing anthracycline and/or trastuzumab administration. Diastolic function impairment may precede or not LVEF decrease. In conclusion, recent studies have provided novel insights into the possible role of radionuclide angiography in the early detection of cancer therapy cardiotoxicity. While interpreting the results of a radionuclide angiography examination, an integrated approach combining the evaluation of LVEF, LV diastolic function, and phase analysis may be useful to improve risk stratification of cancer patients treated with cardiotoxic agents.
