Current treatment in cardiac amyloidosis

Abstract

Involvement of the heart is a common finding in amyloidosis. The heart is usually infiltrated by amyloid fibrils in primary amyloidosis and age-related forms of amyloidosis, less commonly in transthyretin familial amyloidosis, and rarely in secondary amyloidosis. The most common clinical presentation is restrictive cardiomyopathy with right-sided heart failure. The second most frequent presentation is congestive heart failure due to systolic dysfunction, followed by arrhythmias and orthostatic hypotension. The diagnosis of amyloidosis requires tissue sample confirmation; at present, Congo red staining in polarized light is the diagnostic method of choice. The characterization of protein fibril type by immunohistochemistry or biochemistry is essential for patient prognosis and treatment. The therapeutic approach consists of specific treatment of amyloidosis and supportive treatment for cardiac-related symptoms. The treatment depends on the type of amyloidosis and the stage of disease. The mainstay of supportive treatment of cardiac failure is diuretic therapy. Primary amyloidosis treatment protocol includes melphalan and prednisone chemotherapy. Heart transplantation is only a palliative treatment. Stem cell transplantation is an emerging treatment alternative. Combination therapy of melphalan and stem cell transplantation has been shown to be a promising treatment strategy. Secondary amyloidosis requires aggressive treatment of the associated inflammatory and neoplastic process. Age-related (senile) amyloidosis benefits from supportive cardiac treatment when applicable. Transthyretin amyloidosis, the most common cardiac hereditary amyloidosis, is treated by liver or combined liver-heart transplantation. New therapies based on chemical and immunologic reaction with amyloid or its precursor are under intensive development.

Stiff Heart Syndrome

“…2 This is more common in cardiac amyloidosis with primary AL amylodosis and less so with secondary or familial subtypes of the disease. 54 Although, in the U.S.A. and Europe, patients with hereditary amyloidosis caused by variant transthyretin who are young and have minimal symptoms, are usually considered candidates for organ transplant. 2 Ongoing studies are evaluating immunotherapeutic agents, such as monoclonal antibodies, to treat this disease.…”

Cardiovascular Complications in Patients with AL Amyloidosis

“…The long-term prognosis is poor (39% survival at 4 years in one study and 30% at 5 years in another, even with adjuvant chemotherapy. Sequential heart and autologous stem cell transplantation for primary amyloidosis has been reported (42). Active agents in the treatment of the amyloid include corticosteroids (prednisone, dexamethasone), alkylating agents (melphalan, cyclophosphamide), immunomodulatory drugs (thalidomide, lenalidomide) and proteasome inhibitors (bortezomib).Conventional chemotherapy based on melphalan and prednisone was introduced in 1972 can achieve a median survival of 12 to 18 months and in patients with severe cardiac failure, continuous, oral, daily melphalan has been used as palliative method (43).…”

Cardiac Amyloidosis Responding to Bortezomib: Case Report and Review of Literature

“…Its incidence is around 8.9 per million, with peak onset around the sixth decade and male to female ratio of 3:2 [9, 10]. Theoretically, any organ can be infiltrated by light chain.…”

“…It is caused by the deposition of normal transthyretin in multiple organs a mainly atrial cardiac tissue [9, 10]. It is usually clinically unrecognized until massive tissue deposition occurs and leads to heart failure.…”

“…In patients with a predicted poor outcome, the use of lower dose of Melphalan-based regimens is recommended and better tolerated but response is usually delayed [17]. The combination of oral Melphalan and high dose Dexamethasone showed remission in 33% of patients ineligible for stem cell transplantation [10]. Alternative regimens for Melphalan-refractory cases, is the combination of Thalidomide and Dexamethasone [10].…”