Cardiac Amyloidosis: Diagnosis and Treatment Strategies

Abstract

Cardiac amyloidosis in the United States is most often due to myocardial infiltration by immunoglobulin protein, such as in AL amyloidosis, or by the protein transthyretin, such as in hereditary and senile amyloidosis. Cardiac amyloidosis often portends a poor prognosis especially in patients with systemic AL amyloidosis. Despite better understanding of the pathophysiology of amyloid, many patients are still diagnosed late in the disease course. This review investigates the current understanding and new research on the diagnosis and treatment strategies in patients with cardiac amyloidosis. Myocardial amyloid infiltration distribution occurs in a variety of patterns. Structural and functional changes on echocardiography can suggest presence of amyloid, but CMR and nuclear imaging provide important complementary information on amyloid burden and the amyloid subtype, respectively. While for AL amyloid, treatment success largely depends on early diagnosis, for ATTR amyloid, new investigational agents that reduce production of transthyretin protein may have significant impact on clinical outcomes. Advancements in the non-invasive diagnostic detection and improvements in early disease recognition will undoubtedly facilitate a larger proportion of patients to receive early therapy when it is most effective.

The Clinical Spectrum of Amyloidosis

“…Again, there is the caveat that early in the disease process these findings may not be evident. A longitudinal "strain" pattern may also be present, but again is not a specific finding for amyloidosis [35]. Technetium-99 pyrophosphate scanning of the heart, particularly with single photon emission computed tomography (SPECT), is a sensitive imaging technique that will show retention of the radionuclide in cases of cardiac amyloidosis; this is widely considered a diagnostic study of choice.…”

Imaging cardiac innervation in hereditary transthyretin (ATTRm) amyloidosis: A marker for neuropathy or cardiomyopathy in case of heart failure?

“…2 Hereditary transthyretin (TTR)-derived amyloidosis (mutant transthyretin, ATTRm) and senile transthyretin-derived amyloidosis (wild-type transthyretin, ATTRwt) are the two types of systemic amyloidosis that originate from TTR 1,3 and both are associated with cardiac involvement. 4,5 Endomyocardial biopsy is currently the gold standard for diagnosing cardiac amyloidosis, [6][7][8] but this procedure is time consuming with an increased risk of complications, such as arrhythmias, puncture of central arteries, pneumothorax, and perforation with pericardial tamponade. 9 While searching for noninvasive alternatives, Nterminal pro-B-type natriuretic peptide (NT-proBNP) [10][11][12] and autonomic function tests became of value as markers of cardiomyopathy and cardiac autonomic neuropathy, respectively.…”

Analysis of gene expression profiling of amyloidogenic immunoglobulin light‑chains on cultured rat cardiomyocytes

“…Although this disease was identified in the mid-19th century, the mortality rate remains high, resulting from a difficult early diagnosis and few effective treatment options (4). Patients with cardiac amyloidosis usually present with symptoms of heart failure, angina and conductive delays (3,5). Cardiac biomarkers, such as serum cardiac troponin and brain natriuretic peptide (BNP), are sensitive markers of cardiac dysfunction and the levels are elevated in amyloidosis (3,5,6).…”

“…Patients with cardiac amyloidosis usually present with symptoms of heart failure, angina and conductive delays (3,5). Cardiac biomarkers, such as serum cardiac troponin and brain natriuretic peptide (BNP), are sensitive markers of cardiac dysfunction and the levels are elevated in amyloidosis (3,5,6). Treatment of cardiac amyloidosis depends on a combination of therapies aimed at controlling hematologic disorders and relieving cardiac damage (5).…”

“…Cardiac biomarkers, such as serum cardiac troponin and brain natriuretic peptide (BNP), are sensitive markers of cardiac dysfunction and the levels are elevated in amyloidosis (3,5,6). Treatment of cardiac amyloidosis depends on a combination of therapies aimed at controlling hematologic disorders and relieving cardiac damage (5). Heart failure in cardiac amyloidosis faces specific therapeutic challenges in the clinic.…”