Sara Rosengren: AL amyloidosis: Study of epidemiology, diagnosis and treatment with emphasis on heart involvement

Abstract

AL (immunoglobulin light chain) amyloidosis is often associated with delayed diagnosis and thereby high early mortality that is not overcome by contemporary treatment. There is a need for diagnostic methods promoting earlier diagnosis, especially in patients with cardiac involvement. Progress has been made in the treatment of AL amyloidosis and prolonged survival has been reported from specialized referral centers. However, population-based reports are scarce regarding epidemiology as well as treatment outcomes. Aims of this thesis were to increase the knowledge of the epidemiology of AL amyloidosis, investigate new imaging methods for early diagnosis and prognostication in cardiac amyloidosis (CA), and evaluate treatment options with focus on patients with cardiac involvement. 

In paper I we presented real-world long-term results of treatment with high dose chemotherapy for AL amyloidosis in Sweden. We could conclude that long overall survival (median 8.2 years, 95% CI 5.1-11.2) was reached with high dose chemotherapy, but with inferior outcomes in patients with cardiac involvement. Treatment related mortality was comparable to that reported from larger centers during this period and was decreasing from 23.8% to 7.8% during the studied time period.

In paper II we studied the accuracy of PET with the amyloid binding tracer 11C-PIB for the diagnosis of CA. 11C-PIB PET showed high accuracy in detecting CA, and affinity was higher for AL compared to transthyretin amyloidosis. We concluded that 11C-PIB PET can be a useful method to rule in or out amyloidosis in patients with unexplained diastolic heart failure. Our results also indicated that 11C-PIB PET can detect CA at an earlier stage than echocardiography and might be a useful tool for early diagnosis.

In paper III we studied the prognostic value of cardiac function parameters from 11C-acetate PET in CA. We found that reduced myocardial external efficiency was associated with inferior survival in CA patients. However, the strongest prognostic parameter was lowered ratio of forward stroke volume and left ventricular mass, which was the only independently prognostic parameter in multivariable analysis. 

Paper IV was a population-based epidemiological study in which we could determine the standardized incidence of systemic AL amyloidosis to 12.0 (95% CI 9.3-14.7) per million person-years for Uppsala County, without significant change during the period 2000-2020. The 5-year limited duration prevalence increased numerically, but without statistical significance. Prolonged overall survival was observed over time, and there was also a decrease in early mortality, indicating earlier diagnosis of especially patients with cardiac involvement.