ASO treatment of patients with moderate to advanced ATTR cardiomyopathy shows indication of stabilization of disease progression and may therefore contribute to enhanced life expectancy.

Background: Cardiomyopathy is a major cause of death in patients with systemic transthyretin amyloidosis. Long term effect of therapy designed to inhibit hepatic production of the amyloid precursor has not been established in cardiomyopathy. The purpose of this study was to evaluate the long term safety and efficacy of transthyretin specific antisense oligonucleotide therapy, inotersen, in transthyretin cardiomyopathy. Methods: Patients with hereditary or wildtype transthyretin cardiomyopathy (NYHA I-III) with an LV wall thickness ! 1.3 cm and clinical evidence of congestive heart failure were eligible for this single centre, open label protocol. Safety and cardiac structural and functional parameters were prospectively studied. Results: As of October 2018, 33 subjects have entered the study. Twenty have completed 1 year, 16 have completed 2 years, and 14 have completed three years. At the 2 year time point, mean LV mass decreased by 8.4% as measured by MRI, and exercise tolerance increased by 20.2 metres as measured by 6 minute walk test. Further positive indicators were noted at 3 years, with LV mass decreasing by 11.4% and 6MWT increasing by 16.2 metres. Conclusion: Long term treatment of amyloid cardiomyopathy with inotersen is safe and effective in inhibiting progression and potentially reversing amyloid burden.

We prospectively studied 331 sarcoma patients treated between April 1999 and December 2004 to see if small, indeterminate pulmonary nodules are of prognostic significance. Seventy-one (21%) had indeterminate pulmonary nodules on initial spiral CCT. Twenty of 71 (28%) patients with indeterminate nodules progressed with metastatic disease. Metastatic disease developed in 18/20 (90%) in the area of the original indeterminate nodule. The presence of tiny (<5 mm) indeterminate nodules was not a prognostic variable, however, the presence of nodules > or =5 mm was associated with worse 3 year disease-free survival compared to those with no nodules or tiny nodules (81% versus 49%) but better than those with definite metastatic disease at presentation (49% versus 5%). Because patients with pulmonary nodules > or =5 mm are at increased risk for metastatic disease compared to patients with normal CCT or those with <5 mm nodules but better survival than patients with Stage IV disease, we believe a new staging system of these patients should be considered and recommend careful followup.

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