The natural history of de novo cardiac amyloidosis is poorly described, a limitation that makes clinical decision-making difficult given the growing number of therapies for light-chain (AL)-amyloidosis (AL). We identified all patients presenting to our center from 3/99 to 8/07 at, or within 4 months of, diagnosis with symptomatic cardiac amyloidosis, and analyzed the baseline and post-treatment factors influencing survival for those with AL. During that period, 34.5% (157/455) of amyloid patients were diagnosed with de novo cardiac amyloidosis: 112 men and 45 women with a median age of 62 (31–83). Heart biopsies were obtained and were positive in 39% of men (44/112) and 31% of women (14/45). AL was diagnosed in 86% of patients (n=135) and hereditary (n=7) and senile cardiac (n=15) in the rest. Eight patients underwent heart transplant for hereditary (2 men) and AL (5 men, 1 woman). AL was diagnosed in 81% of men and 98% of women (p=0.005, chi square). We analyzed survival from diagnosis based on intention-to-treat. Ninety percent of patients with AL (n=122) received chemotherapy. Hematologic responses were scored as complete (CR), partial (PR, > 50% reduction) or non. Patients received IV melphalan with stem cell transplant (SCT, n=45), oral melphalan and dexamethasone (MDex, n=42) or other regimens (n = 35). Selection for SCT was based on age and extent of organ disease. Thirty-eight patients (28%) subsequently received second- and third-line therapies. The median survival for all patients was 10 months (range, 1 to 94). Baseline predictors of survival included age, gender and troponin I. Patients ≤ 60 years old had a median survival of 22 and those > 60 of 8 months (p=0.007). Women had a median survival of 24 and men of 8 months (p=0.02). Patients with troponin I ≤ 0.10 lived a median of 21 and those with levels > 0.10 of 9 months (p=0.01). Median ages at diagnosis of the 91 men and 44 women with AL were 59 (31–83) and 63 (38–82) respectively (p=0.19), and there were no differences in baseline albumin, alkaline phosphatase, CRP, brain natriuretic peptide, troponin I or clonal free light chains. There was a significant difference in serum creatinine (medians of 1.35 and 1.00 in men and women, p < 0.01). Overall, 60% of patients responded to chemotherapy: 55% of men and 74% of women (p=0.04, chi-square). Responders lived a median of 40 and non-responders 7 months (p<0.0001), and there was no difference in median survival based on gender. With SCT, mobilization-related and 100-day mortality was 6.7% (3/45, all men) and deaths due to progression of disease after mobilization pre-SCT were 11% (5/45, 4 men, 1 women). With SCT the median survival is not yet reached, median follow up of survivors is 39 mos (range 12–94), and there is no difference in median survival by gender. With MDex, the median survival is 14 months and for men is 9 and for women 20 months (p=0.08). With other therapies the median survival is 7 months with no difference by gender. In patients who received second- and third-line therapies median survival is 37 months. In sum, in patients with de novo cardiac AL, factors influencing survival include age, gender, troponin I and response to therapy. Achievement of a prompt hematologic response should be a primary goal of initial therapy and should guide adjuvant and second-line treatments. The gender-related difference in overall survival with cardiac AL merits further study.

Author notes

Disclosure:Consultancy: Consultancy with Millenium.Research Funding: Research Support from Johnson & Johnson, Millenium and Celgene.