Treatment of transthyretin His88Arg amyloidosis with RNA interference therapy: A case report.

A new class of medicines called small interfering RNA molecule has demonstrated beneficial effects in patients with amyloidosis associated with mutations in transthyretin genes (ATTRv), but therapeutic effects towards His88Arg mutation were unknown. Here, we present two challenging cases of patisiran treatment for His88Arg variant. The first case is a 50-year-old male patient diagnosed with transthyretin amyloidosis cardiomyopathy with His88Arg mutation. Administration of patisiran 0.3 mg/kg every three weeks did not show any change in his symptoms. Echocardiography performed 1-year after drug initiation revealed progression of LV hypertrophy and systolic dysfunction with increased pleural effusion. The second case was a 63-year-old woman with heart failure (HF) caused by ATTRv cardiomyopathy with a His88Arg mutation. The patient began patisiran treatment 0.3 mg/kg every three weeks. Eleven months after beginning patisiran, her HF signs worsened with exacerbation of lung congestion and pleural effusion, resulting in hospitalization for decompensated HF. The two cases showed that treatment with patisiran for the patients with advanced stage of His88Arg ATTRv cardiomyopathy was unable to stop the progression of HF. Since the therapeutic response for each variant in ATTRv cardiomyopathy is unknown, further assessment of clinical efficacy for each individual variant is needed. <Learning objective: Asian patients with His88Arg mutation in transthyretin amyloidosis also showed severe cardiomyopathy, as previously reported. Our use of a small interfering RNA molecule, patisiran, for advanced cardiomyopathy of amyloidosis associated with mutations in transthyretin genes (ATTRv) with a His88Arg mutation did not stop the exacerbation of heart failure. The effectiveness of patisiran is expected by starting the administration from early stage of heart failure. It is important not to delay the diagnosis of ATTRv, especially cardiac-type.>.