Prognostic implications of clinical phenotype and severity of cardiac involvement in patients presenting with immunoglobulin light chain amyloidosis
Authors: Porcari A , Masi A , Ioannou A , Patel R K , Razvi Y , Venneri L , Martinez-Naharro A , Sinagra G , Wechelakar A , Hawkins P N , Gillmore J D , Fontana M 
Published: October 2022

Abstract

Background
Patients with systemic immunoglobulin light chain (AL) amyloidosis may present with a wide array of signs and symptoms due to the multi-systemic organ involved. The presence of cardiac involvement is the key determinant of survival. Cardiac magnetic resonance (CMR) has the unique ability to measure the continuum of cardiac amyloidosis (CA) infiltration providing a deep characterisation from early CA involvement to severe degree of CA burden.

Purpose
The aim of this study was to characterise the clinical profiles and the severity of organ involvement in patients presenting with AL amyloidosis and to investigate implications for long-term outcome.

Methods
Patients newly diagnosed with AL amyloidosis at the National Amyloidosis Centre underwent comprehensive clinical, laboratory and instrumental work up, including CMR imaging with left ventricular (LV) mass, late gadolinium enhancement (LGE) and extracellular volume (ECV). The clinical phenotypes were classified in cardiac, renal and other according to the symptoms at presentation. The degree of CA was investigated by CMR: 0= no features of CA (normal LV mass, no LGE and normal ECV); 1=early cardiac amyloid infiltration (normal LV mass, raised ECV no LGE); 2= characteristic of CA with normal mass (diffuse subendocardial or transmural LGE, altered gadolinium kinetics and raised ECV); 3= characteristic of CA with elevated mass (diffuse subendocardial or transmural LGE and raised ECV). The study outcome was all-cause mortality.

Results
The study population included 241 AL patients presenting with cardiac and renal (22.8%, n=55), cardiac (28.2%, n=68), renal (33.2%, n=80) and other (15.8% n=38) phenotypes. During a median follow up of 33 (IQR 7–52) months, cardiac phenotype either in isolation or in combination with renal phenotype was associated with a higher rate of all-cause mortality compared to the others (p&lt;0.001) (Figure). On CMR imaging, 43.2% of patients without cardiac phenotype (49%, n=118/241) had characteristic scans of CA (CMR grade 2 and 3) whilst 13.8% of patients with cardiac phenotype (51%, n=123/241) had no features of CA on CMR images (CMR grade 0) in (p&lt;0.001). With Kaplan Meier analysis, the risk of all-cause death increased in patients with characteristic features of CA on CMR scan (Figure 1) and in patients with cardiac phenotype and features of CA on CMR scans compared to the others (both p&lt;0.001) (Figure). At multivariable analysis, age at diagnosis (hazard ratio [HR] 1.03, p=0.009), clinical phenotype at presentation (HR 1.35, p=0.014) and ECV measured by CMR (HR 56, p&lt;0.001) emerged as independent prognostic parameters.

Conclusions
Patients with newly diagnosed AL amyloidosis present most frequently with renal and cardiac phenotypes. CMR detects CA in &gt;40% of patients with non-cardiac phenotype. ECV is an independent predictor of all-cause mortality across the full clinical spectrum of AL amyloidosis.

Funding Acknowledgement
Type of funding sources: None.