Diagnosis of cardiac amyloidosis: a systematic review on the role of imaging and biomarkers

Abstract

BackgroundCardiac Amyloidosis (CA) pertains to the cardiac involvement of a group of diseases, in which misfolded proteins deposit in tissues and cause progressive organ damage. The vast majority of CA cases are caused by light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). The increased awareness of these diseases has led to an increment of newly diagnosed cases each year.MethodsWe performed multiple searches on MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews. Several search terms were used, such as “cardiac amyloidosis”, “diagnostic modalities cardiac amyloidosis” and “staging cardiac amyloidosis”. Emphasis was given on original articles describing novel diagnostic and staging approaches to the disease.ResultsImaging techniques are indispensable to diagnosing CA. Novel ultrasonographic techniques boast high sensitivity and specificity for the disease. Nuclear imaging has repeatedly proved its worth in the diagnostic procedure, with efforts now focusing on standardization and quantification of amyloid load. Because the latter would be invaluable for any staging system, those spearheading research in magnetic resonance imaging of the disease are also trying to come up with accurate tools to quantify amyloid burden. Staging tools are currently being developed and validated for ATTR CA, in the spirit of the acclaimed Mayo Staging System for AL.ConclusionCardiac involvement confers significant morbidity and mortality in all types of amyloidosis. Great effort is made to reduce the time to diagnosis, as treatment in the initial stages of the disease is tied to better prognosis. The results of these efforts are highly sensitive and specific diagnostic modalities that are also reasonably cost effective.

Clinical Analysis of Cardiac Involvement in 53 Patients With Multiple Myeloma Coexistent With Light Chain Amyloidosis

“…These data shows that occurrence of AL and its severity significantly affect the survival of patients with MM, even in the current new drug era. 2,12,[16][17][18][19][20][21][22][23][24][25][26] Although a high level of baseline 24-hour proteinuria has been proposed as a marker of renal involvement and progression of renal dysfunction, our current research data showed that kidney involvement does not have a major impact on survival, similar to existing research results. 2,21 Forty-eight percent of patients who showed abnormal genes of TP53 deletion, and t(14;16) and 1q21 amplification had shorter OS than other patients (8 vs. 26.5 months), favoring the adverse effects of these high-risk genes on survival.…”

Imaging in patients with suspected acute heart failure: timeline approach position statement on behalf of the Heart Failure Association of the European Society of Cardiology

“…In the diagnostic workup of cardiac amyloidosis, nuclear imaging with bone tracers, including [99mTc]‐DPD and [99mTc]‐PYP, may reliably detect ATTR amyloidosis and discern it from AL type …”

“…73 In the diagnostic workup of cardiac amyloidosis, nuclear imaging with bone tracers, including [99mTc]-DPD and [99mTc]-PYP, may reliably detect ATTR amyloidosis and discern it from AL type. 74 Labelling of metaiodobenzylguanine with radioactive 123-iodine (123I-MIBG) enables scintigraphic visualization of the pre-synaptic sympathetic nerve endings and depicts the status of cardiac innervation, which is associated with the prognosis of HF patients. [75][76][77] Of note, according to 123I-MIBG imaging, a temporary decrease of norepinephrine uptake in the myocardium is typical for an exacerbation of HF and may be a potential therapeutic target.…”

Periodic breathing: Fine tuning the phenotype

“…The strengths of their study were the large subject numbers, the use of a standardized analysis algorithm and relative simplicity of the measurements (which can be easily assessed by the human eye). All patients had cardiac MR scans in addition to echocardiography, an important factor given that gadolinium MR scanning is sensitive to identifying cardiac amyloid, a condition estimated to occur in ~25% of HF in patients aged >80 years (autopsy data), is often missed by clinicians and is less responsive to guideline‐based medical therapy …”

“…All patients had cardiac MR scans in addition to echocardiography, an important factor given that gadolinium MR scanning is sensitive to identifying cardiac amyloid, a condition estimated to occur in~25% of HF in patients aged >80 years (autopsy data), is often missed by clinicians and is less responsive to guideline-based medical therapy. 10 Limitations of the study were the ASV randomization; the lack of oronasal flow (patients with HF often hyperventilate and need to mouth breath); and lack of measures of sleep quality, lung function, autonomic activity and ventilation (PaCO 2 ), which might also possibly contribute to prognosis. Moreover, oximeter settings (averaging time and storage capacity) can affect the placement of the SpO 2 nadir in relation to CSR and thus LPCT.…”