Cardiac biomarkers are prognostic in systemic light chain amyloidosis with no cardiac involvement by standard criteria

Abstract

Patients with systemic immunoglobulin light chain amyloidosis (AL) with no evidence of cardiac involvement by consensus criteria have excellent survival, but 20% will die within 5 years of diagnosis and prognostic factors remain poorly characterised. We report the outcomes of 378 prospectively followed Mayo stage I patients (N-terminal pro b-type natriuretic peptide <332 ng/L, high sensitivity cardiac troponin <55 ng/L). The median presenting N-terminal pro b-type natriuretic peptide was 161 ng/L, high sensitivity cardiac troponin 10 ng/L, creatinine 76 μmol/L and mean left ventricular septal wall thickness, 10 mm. Median follow up was 42 (1-117 months), with 71 deaths; median overall survival was not reached (78% survival at 5 years). Although no patients had cardiac involvement by echocardiogram, a proportion (n=25/90, 28%) had cardiac involvement by cardiac magnetic resonance imaging. Age, autonomic nervous system involvement, N-terminal pro b-type natriuretic peptide >152 ng/L, high sensitivity cardiac troponin >10 ng/L and cardiac involvement by magnetic resonance imaging were predictive for survival; on multivariate analysis only N-terminal pro b-type natriuretic peptide >152 ng/L (P<0.008, hazard ratio [HR] 3.180, confidence interval [CI]: 1.349-7.495) and cardiac involvement on magnetic resonance imaging (P=0.026, HR=5.360, CI: 1.219-23.574) were prognostic. At 5 years, 70% of patients with N-terminal pro b-type natriuretic peptide >152 ng/L were alive. In conclusion, N-terminal pro b-type natriuretic peptide is prognostic for survival in patients with no cardiac involvement by consensus criteria and cardiac involvement is detected by magnetic resonance imaging in such cases. This suggests that N-terminal pro b-type natriuretic peptide thresholds for cardiac involvement in AL may need to be redefined.

Figure 1

Survival curves for Mayo stage I patients demonstrating. (A) Overall survival was not reached; overall survival at 1, 3, and 5 years was 95%, 87% and 76% respectively. (B) The impact of haematological response to treatment at six months and survival outcomes, patients achieving a complete response to treatment versus not a complete response (log rank P<0.001). (C) N-terminal pro b-type natriuretic peptide (NT-pro-BNP) above and below 152 ng/L showing poorer outcome for patients with NT-proBNP >152 ng/L, (log rank P=0.001). (D) Cardiac magnetic resonance imaging findings demonstrating a significantly poorer outcome for patients with cardiac amyloid deposition, (log P=0.007)

Figure 2

The difference in N-terminal pro b-type natriuretic peptide (NT-pro-BNP) between patients with, and without, evidence of cardiac involvement on cardiac magnetic resonance imaging (CMR).

Figure 3

Cardiac magnetic resonance image of a patient with no evidence of cardiac amyloidosis by echocardiogram and NT-BNP <332 ng/L showing characteristic features of cardiac involvement. (A) Four-chamber steady state free precession (SSFP) cine (top right panel). (B) Corresponding native T1 map (top left panel) with an elevated value of 1209 m. (C) Corresponding phase sensitive inversion recovery late gadolinium enhancement (PSIR LGE) image showing subendocardial LGE (bottom right panel).(D) Corresponding extracellular volume (ECV) map with an elevated value of 0.47 (bottom left panel).