#2757 Clinical course and prognostic factors in amyloidosis
Authors: Chiappini Maria Grazia , Proietti Emanuela , Vaiarello Valentina , Muzi Lina , Palazzetti Daniela , Strizzi Camillo Tancredi , Pesce Francesco 
Published: May 2024

Abstract

Background and Aims
Early diagnosis and specific therapy are crucial for the prognosis of patients with systemic amyloidosis. The aim of this single-center retrospective study was to evaluate the clinical course and identify prognostic factors associated with survival in a large cohort of patients from the Regional Reference Center “Gemelli Isola” in Rome, Italy.

Method
A total of 244 patients with amyloidosis were studied, including 100 with AL (63 M, 37 F, mean age 64 ± 13 yrs), 18 with AA (3 M, 15 F, mean age 57 ± 21 yrs), 9 with amyloidosis due to myeloma (MM) (5 M, 4 F, mean age 65 ± 15 yrs), 69 with ATTR mutant (38 M, 31 F, mean age 63 ± 15 yrs), 33 with ATTR wild-type (31 M, 2 F, mean age of 70 ± 10 yrs) 2 with Apolipoprotein (1 M, 1 F, mean age 60 yrs), and 15 unclassified amyloidosis (AX) (9 M, 6 F, mean age 63 ± 9 yrs). We considered several parameters, comprising gender, age, type of amyloidosis, time interval between disease onset and diagnosis, clinical signs and symptoms at onset and diagnosis, biochemical parameters, score of renal involvement (RI) (absent, proteinuria, nephrotic syndrome, and eGFR &lt; 60 ml/min), score of cardiac involvement (CI) (absent, hypertrophic cardiopathy, dilated cardiopathy, arrhythmias and heart failure) at onset, diagnosis, and follow-up (FU). Renal outcome was defined as renal replacement therapy (RRT) initiation. The diagnosis of amyloidosis was histologically confirmed in all patients by Congo red stain, immunohistochemical classification and specific diagnostic criteria. Data were collected at diagnosis and retrieved dating back to the clinical onset. The impact of treatment was evaluated, in terms of clinical course and prognosis.

Results
Regardless of the amyloidosis type, between the onset and diagnosis clinical signs and symptoms significantly worsened and the involvement of affected organs increased. The median time from disease onset to diagnosis was 12 months for AL, AX, and MM, and 36 and 37 months for AA and ATTR. RI increased in all patients, from 47% at onset to 65% at diagnosis, and 71% during FU (p &lt; 0.001). In the AL subgroup an eGFR &lt; 60 ml/min was identified in 16% of patients at onset, 37% at diagnosis and 51% at FU (p &lt; 0.001). As expected, in the mutant ATTR group RI was identified in only a small proportion of patients and an eGFR &lt; 60 ml/min was found only in 2% of patients at onset and at diagnosis and in 6% at FU. CI was observed in 77% of all patients at onset, 88% at diagnosis and 98% at FU (p &lt; 0.001). In the AL subgroup, at onset there was a high prevalence of hypertrophic cardiopathy (65%), while at FU there was a significant increase in the prevalence of heart failure (51%) (p &lt; 0.001). In the mutant ATTR group, at onset, hypertrophic cardiopathy was present in 80% of patients while, at FU, heart failure was present in 64%. The median global survival time was 8 years (IC 95%, 7-12 yrs). RRT was started in 28% of patients. Survival curves according to renal and cardiac scores are shown in Fig. 1. Mortality at 6 years was statistically significative in patients with RI (p &lt; 0.005). Survival curve according to renal or cardiac vs RI and CI is shown in Fig. 2. The univariate analysis demonstrated that progressive cardiac impairment from onset to FU, the number of organs involved, serum creatinine, albumin and eGFR had a significant impact on survival (HR of 18.46, CI 95% = 2.57-132.79; HR = 1.33, CI 95% = 1.09-1.62; HR = 1.47, CI 95% = 1.05-2.05; HR = 0.37, CI 95% = 0.24-0.56; HR = 0.99, CI 95% = 0.98-0.99). The multivariate analysis was based on the ‘forward stepwise’ method to select the significant predictors of mortality. The number of organs involved, age at onset, CI at onset, albumin and progressive worsening of CI from onset to FU, significantly impacted on survival (HR = 1.30, CI 95% = 1.02-1.65, p = 0.031, HR = 1.03, CI 95% = 1.01-1.05; HR = 2.08, CI 95% = 1.20-3.60; HR = 0.33, CI 95% = 0.21-0.53; HR = 21.40, CI 95% = 2.95-155.14).

Conclusion
The diagnosis of amyloidosis is often delayed. Prognosis is significantly influenced by the degree of CI and RI, serum albumin, age at onset and the number of organs involved. Better diagnostic accuracy and the availability of novel therapies have however significantly improved survival rates.