28.5.1 Cardiac amyloidosis

The deposition of amyloid fibrils in the heart leads to heart dysfunction, as the cardiomyocytes become distorted and separated and the whole tissue stiffens [1167]. At diagnosis, around half of all AL amyloidosis patients have symptomatic cardiac involvement [1167]. The most common symptom is heart failure with a preserved ejection fraction, but arrhythmias, syncope, ischemic heart disease, cardiomyopathy and thrombosis are also seen [1167]. Cardiac involvement in AL amyloidosis leads to a poorer outcome, and is correlated with the extent of cardiac deposition and severity of cardiac involvement [1167][1168][1169]. Cardiac involvement is the leading cause of death in AL amyloidosis patients [628] and delayed diagnosis is correlated with shorter overall survival [1170] therefore rapid, correct diagnosis is vital.

To make a diagnosis of cardiac AL amyloidosis can present a challenge, firstly due to the range of symptoms, which are not specific to the condition, and secondly because cardiac amyloidosis can be caused by a number of different amyloidogenic proteins [1167]. The three most common amyloidogenic precursor proteins are immunoglobulin light chains (AL), wild type transthyretin (wt ATTR) and mutant transthyretin (ATTR) [1177][1171][1172][1173]. It is important to identify which protein has formed the deposits, as the treatment for each form of amyloidosis is different, and what is effective for one may not be effective for another [1174]. Identification of the amyloidogenic protein is of increased importance in aging populations, where cardiac deposition caused by wt ATTR may occur in monoclonal gammopathy patients [1175].

The diagnostic criteria for AL amyloidosis with cardiac involvement is the same as for AL amyloidosis in general (Section 28.3). Several groups have developed screening algorithms to identify AL amyloidosis in patients who present with cardiac symptoms [1173][1174][1176]. The protocol developed by Gertz et al. [1173][1174] aimed to identify AL, wt ATTR and ATTR amyloidosis in cardiac patients with the use of minimally invasive tests. The authors proposed an initial screen of sIFE, uIFE and sFLC analysis and if a monoclonal protein is detected, a fat aspirate and a bone marrow biopsy are performed to confirm diagnosis. In his 2018 update to the algorithm [1174], Gertz proposed the addition of a pyrophosphate uptake scan to the algorithm to help detect ATTR cardiac deposits.

Once cardiac AL amyloidosis is diagnosed, measurement of cardiac biomarkers and sFLCs are useful for determination of the prognosis (Section 28.8.1), and can also be used to monitor response to therapy (Section 28.7).