Cardiac related death in thalassaemia major: time trend and risk factors in a large Greek Unit

Cardiac complications are the leading cause of death in thalassaemic patients (TM) worldwide. Improved management protocols including new chelators and imaging have reduced cardiac-related deaths but also require more advanced analytical methods to reflect temporal fluctuations in mortality risk. To evaluate time patterns of risk of cardiac death in TM patients according to birth cohort, gender and degree of haemosiderosis and to apply new flexible methods of analysis that may allow assessment of trends in risks as affected by innovations in management. Cardiac-free survival and time trend of the risk of cardiac-related death were assessed in 648 transfusion-depended thalassaemic patients (48.3% females) managed in a single unit located in Athens, Greece. Patients were classified according to birth cohort (prior or after 1/1/1975) and according to the severity of haemosiderosis (mild, moderate and severe) as estimated by the mean ferritin levels during the last 5 yr of follow-up. The median time of observation was 27.8 yr and 84 cardiac deaths were recorded. A parametric analysis predicted a non-monotonous time pattern for the cardiac risk with an initial increasing phase until the fourth decade of life followed by a drop off in deaths. Women have 23% longer life expectancy than men (P = 0.010) while patients born after 1975 die of heart complications at an older age compared to those born prior to 1975 (time ratio = 1.34, P = 0.003). Patients with mild and moderate haemosiderosis lived 89% (P < 0.001) and 43% (P < 0.001) longer, respectively, compared with patients with severe haemosiderosis. These results on risk of death in thalassaemia, accord with expectations. This type of analysis will be useful in the future when the expected impact of cardiac MRI with appropriate tailoring of chelation therapy using all current and future options will modify the pattern of risk of cardiac death observed to date.