Cardiac Amyloidosis: Evolving Approach to Diagnosis and Management

Abstract

The systemic amyloidoses are a group of heterogeneous disorders characterized by extracellular deposition of misfolded fibrillar protein that results in organ dysfunction. Involvement of the heart (cardiac amyloidosis) is manifest by increased cardiac wall thickness and impairment of myocardial diastolic and systolic properties, changes that result in heart failure, dysrhythmia, and death. Amyloidosis is classified by precursor protein, with light-chain (AL) and transthyretin (TTR) disease being most common in the United States. TTR amyloid can result from misfolding of variant TTR, a genetically inherited disease, or wild-type TTR, an acquired form of disease (termed senile systemic amyloidosis). In recent years, advances in the diagnosis and treatment of cardiac amyloidosis include identification and validation of disease biomarkers, new imaging techniques, and consensus treatment guidelines. Elevations of B-type natriuretic peptide and cardiac troponins can identify cardiac amyloidosis with a high degree of precision and confer important prognostic information. Non-invasive cardiac imaging techniques, such as cardiac magnetic resonance imaging and echocardiography with strain quantification, afford the ability to diagnose cardiac amyloidosis most often without the need for a confirmatory heart biopsy. Treatment of heart failure resulting from cardiac amyloidosis differs in many respects from most other etiologies of cardiomyopathy. The mainstay of treatment involves volume control with diuretics, low dose β-adrenergic antagonists or amiodarone for dysrhythmia, and warfarin to prevent thromboembolism. Although widely held to have a dismal prognosis, modern treatments such as high-dose melphalan with stem cell transplantation (HDM/SCT) for AL disease achieve a complete hematologic response in nearly half of eligible patients and yield long-term survival. For patients with advanced AL cardiac amyloidosis, cardiac transplantation followed by HDM/SCT is also an option that has proven highly effective. For familial amyloid derived from variant TTR, liver transplantation is the one validated treatment; however, small molecule therapeutic agents now in clinical trials appear capable of slowing or halting TTR amyloid deposition.

ER Protein Quality Control and the Unfolded Protein Response in the Heart

“…This leads to impaired myocyte contractility, myocyte oxidative stress, and ultimately, myocyte death. Patients diagnosed with this disease typically cannot tolerate standard treatments meant to preserve cardiac function during heart failure, including β-adrenergic receptor blockers, angiotensin converting enzyme inhibitors, and digoxin(Meier-Ewert et al 2011). Another form of cardiac amyloidosis is familial atrial fibrillation, in which the electrical conduction system of the heart, specifically in the atria, is disrupted by deposition of mutant amyloidogenic forms of transthyretin and atrial natriuretic peptide, secreted by the liver and the atria, respectively(Hodgson-Zingman et al 2008).…”

Cardiac amyloidosis: a case review series

“…In AL amyloidosis, treatments against plasma cells include combinations of chemotherapy consisting of dexamethasone, melphalan or other alkylators, lenalidomide, and/or bortezomib [15,16]. In patients with limited cardiac involvement, high dose chemotherapy prior to stem cell transplant is also an option in AL patients [15][16][17].…”

“…In patients with limited cardiac involvement, high dose chemotherapy prior to stem cell transplant is also an option in AL patients [15][16][17]. In select AL patients, i.e.…”

How I treat amyloidosis: the importance of accurate diagnosis and amyloid typing

“…22 Demonstration of abnormal stain rate by pulsed tissue Doppler imaging on echocardiography is more sensitive for early amyloid involvement, but it is not specific. 65,66 In addition, although advanced findings are prognostic, milder cardiac involvement is more difficult to correlate with patient outcomes. Cardiac biomarkers have been extremely helpful in prognostication of these patients.…”