19.1 Amyloid, Sarcoid, and Other Infiltrative Disease Patterns
Key Takeaways
- Echo identifies an infiltrative or storage phenotype through morphology, hemodynamics, deformation, RV and atrial involvement, valves, output, and effusion but does not establish final etiology.
- Amyloid suspicion rises with increased wall thickness, low stroke volume, diastolic and tissue-velocity abnormalities, and relative apical sparing, yet echo cannot distinguish AL from ATTR.
- Sarcoid is often patchy and may produce basal septal thinning, noncoronary regional dysfunction, aneurysm, or biventricular disease while an early TTE remains normal.
- Hemochromatosis, Fabry and other storage disease, endomyocardial fibrosis, hypertension, AS, HCM, CKD, and artifact must be separated through careful acquisition and multimodality context.
Report an infiltrative phenotype, not an unproven etiology
Infiltrative and storage diseases alter myocardium through deposited protein, granulomatous inflammation, iron, abnormal metabolites, fibrosis, or endocardial injury. Echo may be the first clue, but overlapping hypertension, aortic stenosis, hypertrophic cardiomyopathy, chronic kidney disease, athletic remodeling, and obesity can produce similar wall thickening or dysfunction. Review age, blood pressure, valve disease, ECG voltage and conduction, heart-failure pattern, systemic disease, neuropathy, carpal tunnel history, malignancy, inflammatory symptoms, and prior imaging. The echo conclusion should describe the phenotype and degree of suspicion; laboratory testing, genetics, scintigraphy, CMR, PET, or tissue establishes etiology.
Acquire a complete study rather than chasing one signature. Measure LV wall thickness from a perpendicular parasternal plane at end-diastole, excluding RV trabeculation and moderator-band tissue from the septum. Quantify LV mass and volumes, LA and RA volumes, RV wall thickness, size and function, valve thickness and regurgitation, stroke volume, filling parameters, pulmonary pressure, and pericardial effusion. Obtain three nonforeshortened apical views for strain with stable ECG timing, adequate frame rate, and correct endocardial tracking. Preserve vendor, software, loading, rhythm, and image quality for serial work.
Recognize the amyloid constellation
| Domain | Common cardiac amyloid clue | Limitation or mimic |
|---|---|---|
| Morphology | Increased LV and often RV wall thickness, thickened valves or atrial septum, biatrial enlargement | Hypertension, AS, HCM, CKD, and storage disease also increase thickness |
| Hemodynamics | Progressive diastolic dysfunction, elevated filling pressure, low stroke-volume index despite preserved EF | Rhythm, MR, loading, and age alter Doppler; early disease may be subtle |
| Tissue Doppler | Markedly reduced mitral annular e′, a′, and s′ velocities | Angle, annular calcification, tethering, pacing, and sampling error |
| Deformation | Reduced GLS with relative apical sparing | ESRD, HCM, AS, and technical tracking can mimic; not present in every case |
| Associated | Small pericardial effusion, RV dysfunction, low-flow low-gradient AS | Each feature is nonspecific alone |
Relative apical sparing means apical longitudinal strain is less impaired, or more negative, than basal and mid strain. Confirm that the apex is not foreshortened and basal segments are tracked throughout systole. A bull's-eye color pattern is display dependent and should not be called diagnostic or used in isolation. GLS is load-, vendor-, frame-rate-, and tracking-dependent. EF may remain preserved while GLS and stroke volume fall because a thick-walled small cavity ejects a normal fraction of a reduced volume.
The older description of a sparkling myocardium is less specific with harmonic imaging and modern processing. Do not use brightness as a tissue diagnosis. Similar echo features occur in AL and transthyretin, or ATTR, amyloidosis; echo cannot distinguish the protein type. Light-chain evaluation and ATTR pathways carry different urgency and testing, so the sonographer should promptly flag a suspicious constellation without assigning subtype or treatment.
Contrast sarcoid's patchy phenotype
Cardiac sarcoidosis is granulomatous and often regionally heterogeneous rather than uniformly thick-walled. Echo may show focal wall thinning or thickening, particularly basal septal thinning, noncoronary regional wall-motion abnormalities, ventricular aneurysm, LV or RV dilation and systolic dysfunction, MR from papillary involvement or remodeling, pericardial effusion, and pulmonary-hypertension consequences. Conduction disease or ventricular arrhythmia may be the clinical clue even when TTE is normal.
No echo pattern excludes sarcoid, and sensitivity is limited in early or patchy disease. A regional abnormality should be confirmed in orthogonal planes to reject dropout, foreshortening, and coronary-territory ischemia. CMR detects scar and inflammation-related tissue patterns; FDG-PET assesses active inflammation under a dedicated preparation protocol. Those modalities, clinical criteria, and sometimes biopsy determine diagnosis. Echo contributes chamber function, hemodynamics, valve effects, and serial response, not a final inflammatory label.
Recognize other phenocopies and endocardial patterns
| Disease process | Possible echo phenotype | Discriminator outside routine echo |
|---|---|---|
| Hemochromatosis | Early diastolic dysfunction, later dilated or restrictive physiology and reduced biventricular function | Iron studies and CMR tissue characterization |
| Fabry or other storage disease | Concentric LV thickening, prominent papillary muscles, RV thickening, diastolic dysfunction, reduced regional or global strain | Enzyme, genetic, renal, neurologic, and CMR evidence |
| Eosinophilic or endomyocardial fibrosis | Apical endocardial thickening or obliteration, mural thrombus, restrictive filling, AV-valve regurgitation | Blood, systemic, CMR, and sometimes tissue findings |
| Metastatic or inflammatory infiltration | Focal or diffuse myocardial thickening, mass, dysfunction, or effusion | Clinical cancer/inflammation context and multimodality imaging |
Fabry disease is a storage phenocopy rather than amyloid deposition, and iron overload may progress from subtle relaxation change to chamber dilation. Apical obliteration must be distinguished from foreshortening and thrombus; use an ultrasound-enhancing agent under protocol when the border is uncertain. Restrictive filling describes hemodynamics, not etiology, and can occur in advanced myocardial, valvular, or pericardial disease.
Integrate discordant evidence
When wall thickness, ECG, strain, Doppler, and clinical data disagree, first verify measurements and loading. A hypertensive patient can still have amyloidosis; conversely, apical sparing does not erase severe AS or CKD. Report wall thickness and geometry, EF and stroke volume, GLS pattern and quality, diastolic evidence, atrial and RV involvement, valves, pressure, effusion, and interval change. Use language such as “findings raise suspicion for an infiltrative cardiomyopathy” and recommend clinical correlation through the interpreting physician. New severe dysfunction, low output, major effusion, or unstable arrhythmia requires prompt communication under laboratory policy.
Verify interval change
Before calling progression or treatment response, compare image plane, border convention, rhythm, blood pressure, loading, strain platform, and tracking quality. Reanalyze prior source images when a small change conflicts with the overall phenotype.
Apical sparing is a clue, not a diagnosis
Confirm nonforeshortened views and valid tracking, then interpret the strain pattern with wall thickness, stroke volume, Doppler, ECG, and clinical context. Amyloid subtype requires testing beyond echocardiography.
An older adult has increased LV and RV wall thickness, biatrial enlargement, low stroke-volume index, markedly reduced annular tissue velocities, and reduced GLS with relative apical sparing. What is the best echo conclusion?
Which actions make an infiltrative-disease echo assessment more defensible? Select three.
Select all that apply