Abstract
AL (light-chain) amyloidosis and transthyretin-related amylodosis (ATTR), either hereditary or senile, lead to clinically relevant cardiac disease. Recently, increased attention is paid to senile ATTR due to its increasingly frequent capture.
ATTR also represents an example of the disease manifesting as heart failure with preserved ejection fraction due to specific etiology. So far, treatment of ATTR amyloid cardiomyopathy was based on conventional heart failure therapy; orthotopic liver transplantation or combined heart and liver transplantation was indicated only in few cases.
Tafamidis is a TTR-stabilizer that prevents its dissociation and thus subsequent amyloid formation. It is already administered in patients with hereditary ATTR polyneuropathy in order to slow the progression of peripheral neuropathy.
International, randomized, double-blind and placebo controlled ATTR-ACT trial was designed to assess the efficacy and safety of tafamidis in treatment of patients with heart failure due to ATTR amyloid cardiomyopathy. Compared to placebo, 30 months of tafamis therapy had statistically significant effect on both all-cause mortality (30% reduction) and cardiovascular hospitalization (32% reduction).
The change of functional capacity in the 6-minute walk test as well as the quality of life according to the Kansas Cardiomyopathy Questionnaire were also significantly influenced by tafamidis administration. The therapy with tafamidis was safe and well tolerated.
The ATTR-ACT trial therefore clearly demonstrated the positive effect of tafamidis in patients with ATTR amyloid cardiomyopathy and heart failure. The ATTR-ACT trial is the first major study demonstrating the effect of specific therapy in this group of patients who probably represent not a negligible portion of individuals suffering from heart failure with preserved or mildly reduced ejection fraction.