Background

Increased N-terminal pro b-type natriuretic peptide (NT-proBNP) is a known biomarker of cardiac and renal injury in patients with various diseases. Prevalence of cardiac and/or renal impairment is high in patients with systemic amyloidosis.  It remains unclear if combined cardiac and renal involvement is related to more significant increase of NT-proBNP as compared to isolated cardia or renal involvement. In addition, it remains elusive if the level of NT-proBNP increase is proportionally related to higher mortality in these patients.

Methods

This retrospective study included 99 patients with histologically confirmed systemic amyloidosis who admitted in our hospital from 2002 to 2020: isolated renal involvement (n=15), isolated cardiac involvement (n=45), combined cardiac and renal involvement (n=39).  NT-proBNP, estimated glomerular filtration rate, and echocardiography derived cardiac functional features were compared among these patients. All patients completed a one-year clinical follow-up by medical records review or telephone interview, and the primary endpoint was defined as all-cause death or heart transplantation.

Results

In the whole cohort, mean age was 65±10 year, 69.5% of patients were male. Of these, there were 74 patients identified as light-chain amyloid, 14 as wide-type transthyretin amyloidosis, 5 as hereditary transthyretin amyloidosis, and 6 as serum amyloid A.

NT-proBNP level was significantly higher in patients either with cardiac involvement or with combined cardiac and renal involvement as compared to patients with isolated renal involvement (median: 3658 vs. 3822 vs. 405pg/ml, both p<0.05). Estimated glomerular filtration rate remained preserved in patients with cardiac involvement (72 ml/min/1.73qm), while significantly reduced in patients with isolated renal involvement or combined cardiac and renal involvement (47 and 53 ml/min/1.73qm, P=0.011). Cardiac systolic function assessed by echocardiography was similar among three groups (median LVEF: 66% vs. 60% vs. 61%, P=0.204).

During one-year follow up, 19 patients died and 1 underwent heart transplantation. One-year all-cause mortality was 0%, 26.7% and 20.5% in the groups of renal involvement, cardiac involvement, and combined cardiac and renal involvement, respectively (Kaplan-Meier analysis, overall comparisons Log-rank P=0.088; cardiac involvement  vs. renal involvement Log-rank P=0.027; combined cardiac and renal involvement  vs. renal involvement Log-rank P=0.069).

Cox regression analysis showed that increased NT-proBNP  level was independently and significantly associated with increased risk of all-cause mortality in patient with systemic amyloidosis adjusted for age and sex (natural logarithm-transformed NT-proBNP: HR=1.76, 95% CI=1.27-2.45, P=0.001). This association remained significant in the subgroup of cardiac involvement (HR=2.78, 95% CI 1.39-5.57, P=0.004), but not in the subgroup of combined cardiac and renal involvement (HR=1.52, 95% CI=0.87-2.64, P=0.140).

Conclusion: Our results suggest that cardiac involvement, but not renal involvement, is associated with significant NT-proBNP increase and increased one-year mortality in patients with systemic amyloidosis.