Collection of resources
Heart failure
Heart failure (HF) is a complex syndrome with numerous and varied causes, including cardiac amyloidosis. HF is caused by structural and/or functional abnormalities of the heart, which lead to reduced cardiac output and/or high filling pressures at rest or with stress.
ATTR-CM
Transthyretin amyloid cardiomyopathy (ATTR-CM) exists in two sub types: wild type and hereditary. Disease manifestation depends on the sites of amyloid deposition and/or TTR mutation. Symptom overlap can lead to the misdiagnosis of ATTR-CM or a delay in its recognition, yet advanced stages of disease are associated with poorer prognosis, making earlier and accurate diagnosis crucial.
AL amyloidosis
AL-amyloidosis is a form of cardiac amyloidosis caused by monoclonal proliferation of plasma cells. The aggressive nature of the disease, poor prognosis and different treatment strategies mean it is critical to rule out AL amyloidosis at the earliest opportunity in the patient journey.
Red flags
Accurate, early diagnosis of ATTR-CM is key to improving patient outcomes. Diagnostic “red flags” can support the timely recognition of ATTR-CM within the wider population of patients with heart failure (HF). Importantly, ATTR-CM is a heterogenous disease and all patients will not exhibit all “red flags”; however, presence of any of these red flags, together with increased left ventricular (LV) wall thickness should lead to screening.
HFpEF and HFrEF
HFpEF and HFrEF are two major subtypes of heart failure that differ in terms of pathophysiology and aetiology, as well as treatment responses. Patients with cardiac amyloidosis (CA) often present with HFpEF, which is associated with poor quality of life, high rates of hospitalization, and premature mortality.
Hereditary ATTRv amyloidosis
Hereditary/variant ATTR amyloidosis (ATTRv) has a varied presentation depending on the specific underlying mutation. It can manifest as predominantly cardiac, neurologic or a combination of the two phenotypes, and varies depending on the specific genetic mutation present. Two types of amyloid fibrils (A and B) exist, which can give rise to different phenotypes.
Electrocardiography
ATTR-CM can be suspected based on a simple electrocardiographic (ECG) pattern. Discrepancy between left ventricular (LV) thickness and QRS voltage (with lack of LV hypertrophy on ECG) is a red flag for ATTR-CM.
Echocardiography
Echocardiography is an important ultrasound imaging modality that can help raise suspicion of cardiac amyloidosis (CA). There are some key echocardiography signs to look out for that, in context, can be highly suggestive of CA. Concentric left ventricle (LV) hypertrophy, valve thickening, atrial dilation, right heart wall thickness, and a bright “sparkling” myocardium are characteristic features of CA that may be seen with echocardiography.
Cardiac MRI
Cardiac magnetic resonance imaging (cMRI) can be used to aid diagnosis of suspected cases of transthyretin cardiac amyloidosis (ATTR-CM). Quantitative T1 mapping and extracellular volume (ECV) calculation techniques can be very useful in ATTR-CM for early diagnosis, clinical follow-up, and treatment response assessment.
Nuclear scintigraphy
Nuclear scintigraphy, combined with blood and urine tests for free light chains, represents a noninvasive method to differentially diagnose ATTR-CM. It is used to identify patients who have amyloid deposition in the myocardium, with high specificity and sensitivity in patients with ATTR-CM.
Biopsy
Tissue biopsy is an invasive diagnostic test often used to make a definitive diagnosis of cardiac amyloidosis (CA). It is required for a definitive diagnosis of immunoglobulin light chain amyloidosis (AL) but may not always be needed for the confirmation of transthyretin amyloid cardiomyopathy (ATTR-CM), as noninvasive bone scintigraphy can often be sufficient, provided stringent criteria are met.
Cardiac biomarkers
Biomarker levels can be used to stratify patients with HF and predict risk of hospitalisation and mortality. Cardiac biomarkers that may raise suspicion of ATTR-CM include elevation of low-grade persistent troponin (T or I) and elevated levels of NT-proBNP.
Management and treatment
Treatment of ATTR-CM encompasses two arms: supportive therapy and specific treatment. Mechanism of action of specific treatments can be grouped into three main categories: Suppression of TTR, TTR stabilizers and amyloid fibril degraders. A TTR stabilizer is approved by the EMA for the treatment of wild-type or hereditary transthyretin amyloidosis in adult patients with cardiomyopathy (ATTR-CM).
Reference list
Full (total) reference list e-learning.