Cardiac amyloidosis: the great pretender

Abstract

Cardiac amyloidosis (CA) is often misdiagnosed because of both physician-related and disease-related reasons including: fragmented knowledge among different specialties and subspecialties, shortage of centres and specialists dedicated to disease management, erroneous belief it is an incurable disease, rarity of the condition, intrinsic phenotypic heterogeneity, genotypic heterogeneity in transthyretin-related forms and the necessity of target organ tissue histological diagnosis in the vast majority of cases. Pitfalls, incorrect beliefs and deceits challenge not only the path to the diagnosis of CA but also the precise identification of aetiological subtype. The awareness of this condition is the most important prerequisite for the management of the risk of underdiagnoses and misdiagnosis. Almost all clinical, imaging and laboratory tests can be misinterpreted, but fortunately each of these diagnostic steps can also offer diagnostic "red flags" (i.e. highly suggestive findings that can foster the correct diagnostic suspicion and facilitate early, timely diagnosis). This is especially important because outcomes in CA are largely driven by the severity of cardiac dysfunction and emerging therapies are aimed at preventing further amyloid deposition.

Wild-Type Transthyretin Cardiac Amyloidosis: Novel Insights From Advanced Imaging

“…This approach can be challenging, especially in context of large scale population-based screening. EMB is a procedure often restricted to centers with significant expertise in its performance, typically large referral centers with transplant programs 1 . While rare, procedural complications can include arrhythmia, perforation with pericardial tamponade, and pneumothorax 22 .…”

“…Amyloidosis is caused by extracellular deposition of abnormal protein fibrils, resulting in destruction of tissue architecture and impairment of organ function 1 . Amyloidosis may be localized or systemic, and is categorized by the type of precursor protein 2 .…”

“…TTR amyloid predominantly affects individuals of African American descent; Val122lle mutation prevalence has been reported in 3.43% of African Americans under age 65 6 . Wild-type TTR (ATTRwt), previously known as Senile Cardiac Amyloidosis (SCA), is caused by deposition of amyloid fibrils formed from misfolded TTR proteins, and has been described almost exclusively in older adult males 1-3 . While AL Amyloid is a relatively rare disorder, with approximately 3,000 new cases in North America annually 4 , ATTRwt is rapidly increasing in recognition.…”

“…Extra-cardiac manifestations such as peripheral neuropathy may predominate and become the clinical focus 1 . Diagnosis of ATTRwt-CA can also be confounded by the high prevalence of monoclonal proteins that occur with advancing age; up to 20% of elderly patients with TTR cardiac amyloidosis have concomitant monoclonal gammopathy of undetermined significance 1 . Symptoms of ATTRwt-CA are relatively non-specific, and are often attributed to the syndrome of heart failure.…”

Measurement of Troponin in Cardiomyopathies

“…The cardiac phenotype is typically either HCM or RCM and the condition may be inherited (usually due to mutations in transthyretin, TTR) or associated with immunoglobulin light-chain depositiontermed AL amyloidosis. 88 Elevated cardiac Tn levels are associated with a poor prognosis in AL amyloidosis and are routinely used to stage the disease and stratify treatment. 89,90 The role of troponins in wild type TTR related amyloid (ATTR) is less well established but a recent study found levels TnI were higher in patients with ATTR amongst a heart failure with persevered ejection fraction (HFpEF) population.…”