On the Horizon
Clinical trials are now under way to examine pharmacotherapeutic options for patients with ATTR amyloidosis. Now being examined in clinical trials, for example, is Fx-1006A, a drug that stabilizes ATTR and prevents the misfolding of the amyloid protein fibril, in turn preventing it from binding to the target organ.38 Similarly, ALN-TTR, a drug believed to prevent disease manifestation and possibly facilitate disease regression, is being investigated in early human trials.39
Additionally, the use of genetic testing is recommended in at-risk individuals to identify the TTR gene. Affected patients may benefit from prophylactic medical management, which would halt amyloidogenesis of TTR—and possibly treat the condition as well.35 Pharmacotherapeutic agents like diflunisal, an NSAID, antagonize the aggregation of TTR protein and hinder formation of the amyloid fibrils.40
CONCLUSION
ATTR Val122Ile familial amyloidosis is a rare disorder that causes abnormal synthesis of amyloid protein in the liver, which then infiltrates the cardiac structure, leading to restrictive cardiomyopathy and progressive heart failure. Patients who present with symptoms of heart failure, cardiac enlargement on echocardiography, and a finding of granular speckling patterns, though not specific on echocardiography, should prompt the health care provider to refer the patient to a cardiologist familiar with cardiac amyloidosis for further work-up.
Diagnosed patients must undergo genetic testing to determine the specific variant type so that prompt treatment can be initiated. In patients with ATTR Val122Ile familial amyloidosis, the treatment of choice is cardiac transplantation. Although the mutant amyloid protein continues to be synthesized in the liver, the donor heart is unlikely to become affected by this substance for many years. Appropriately treated patients can maintain good quality of life, free of heart failure.
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