Diagnostic Workup for Suspected Cardiac Amyloidosis on Echocardiography
For patients with suspected cardiac amyloidosis on echocardiography, the recommended diagnostic workup should begin with screening for serum and urine monoclonal light chains, followed by bone scintigraphy if negative, and genetic testing if ATTR amyloidosis is confirmed. 1
Initial Assessment of Echo Findings Suggestive of Cardiac Amyloidosis
Echocardiographic findings that suggest cardiac amyloidosis include:
- Left ventricular wall thickness >12 mm
- Relative apical sparing of global longitudinal strain ratio >1
- Grade 2 or greater diastolic dysfunction
- "Granular sparkling" appearance of myocardium
- Thickened valves and interatrial septum
- Biatrial enlargement with small LV cavity
- Pericardial effusion
Diagnostic Algorithm
Step 1: Screen for Light Chain (AL) Amyloidosis
- Obtain serum and urine immunofixation electrophoresis
- Measure serum free light chains
- This is a Class I recommendation (Level of Evidence B-NR) 1
Step 2: If No Evidence of Monoclonal Light Chains
- Proceed with bone scintigraphy (99mTc-PYP, 99mTc-DPD, or 99mTc-HMDP)
- Grade 2-3 myocardial uptake is highly specific for ATTR amyloidosis
- This is a Class I recommendation (Level of Evidence B-NR) 1
Step 3: If ATTR Amyloidosis is Confirmed
- Perform genetic testing with TTR gene sequencing to differentiate:
- Hereditary variant (ATTRv)
- Wild-type (ATTRwt)
- This is a Class I recommendation (Level of Evidence B-NR) 1
Step 4: Consider Additional Testing Based on Clinical Context
- Cardiac MRI if not contraindicated (look for diffuse late gadolinium enhancement, elevated T1 values, and extracellular volume >0.40) 1
- Endomyocardial biopsy if diagnosis remains uncertain despite non-invasive testing 1
- BNP/NT-proBNP and troponin levels (for prognostication and staging) 1, 2
Special Clinical Considerations
Red Flags That Should Prompt Amyloidosis Workup
- Left ventricular wall thickness ≥14 mm with fatigue, dyspnea, or edema
- Discordance between wall thickness on echo and QRS voltage on ECG
- History of carpal tunnel syndrome (especially bilateral)
- History of biceps tendon rupture
- Spinal stenosis
- Autonomic or sensory polyneuropathy
- Heart failure with preserved ejection fraction (HFpEF) resistant to conventional therapy 1
Diagnostic Pitfalls to Avoid
Missing AL amyloidosis: Up to 40% of patients with ATTR cardiac amyloidosis can have monoclonal gammopathy of unknown significance (MGUS). Therefore, positive bone scintigraphy alone is not sufficient for diagnosis without excluding AL amyloidosis through serum and urine testing 1.
Relying solely on echocardiography: While echo is valuable for initial suspicion, it cannot definitively diagnose the type of amyloidosis. The diagnostic algorithm must include specific testing for AL and ATTR types 1.
Delaying diagnosis: Cardiac amyloidosis is a progressive disease with median survival from diagnosis of less than 6 months for AL and 3-5 years for ATTR if untreated. Early diagnosis is crucial as effective treatments are available 3.
Overlooking genetic testing: If ATTR amyloidosis is confirmed, genetic testing is essential to differentiate hereditary from wild-type disease, which has implications for family screening and management 1.
By following this systematic approach, clinicians can efficiently diagnose cardiac amyloidosis, determine its type, and initiate appropriate treatment to improve patient outcomes.