Introduction: Cardiac amyloidosis (CA) is the key determinant of survival in systemic AL amyloidosis. Hypothesis: To assess (i) the differences between serum biomarkers, echocardiography and CMR with ECV mapping in characterising cardiac involvement, (ii) their independent prognostic role, and (iii) the role of ECV mapping to guide treatment strategies. Methods: Consecutive patients newly diagnosed with systemic AL amyloidosis between 2015-2021 who underwent echocardiography, cardiac biomarkers, and CMR with ECV mapping at the time of diagnosis were included. Haematological response (HR) at 1 and 6 months was defined according to validated criteria. The primary outcome was mortality. Results: Five-hundred sixty AL patients were included. The different approaches produced different results in terms of presence and severity of cardiac infiltration (CA present from 48.2% to 93%). Over 40.5 months [IQR 9-58], only ECV was independently associated with mortality (p< 0.001). In the landmark analysis at 1 month, patients with ECV < 0.30 and with ECV 0.31-0.40 had an excellent long-term survival regardless of the achieved HR (p=0.92 and p=0.08, respectively), whilst in patients with ECV > 0.40 survival was dependent on the depth of the HR (p< 0.001). In the landmark analysis at 6 months, patients with ECV < 0.30 had excellent survival regardless of the achieved HR and patients with ECV 0.31-0.40 had excellent survival if achieving at least a PR (inter-group p=0.006 in NR vs PR). In ECV 0.41-0.50 and ECV > 0.50, long-term survival was excellent only among patients achieving CR (inter-group p< 0.05 in CR vs VGPR). Reaching a deep HR at 1 month vs 6 months was associated with better survival in ECV > 0.40 (p< 0.05), but not in ECV < 0.40. Conclusions: ECV mapping in systemic AL amyloidosis is the only independent predictor of prognosis. ECV mapping can define optimal depth and rapidity of the HR for each patient and inform treatment strategies.