AL type cardiac amyloidosis: a devastating fatal disease

Figures & data

Figure 1. EKG showing diffuse low voltage QRS present in all leads

Figure 2. Echocardiogram demonstrating bi–atrial enlargement, biventricular hypertrophy, hypertrophied thickened interventricular septum and apical sparing on longitudinal strain

Figure 3. Histopathology images demonstrating cardiac amyloidosis

Table 1. Types of Cardiac Amyloidosis [2–4]

Types of cardiac amyloidosis	Comment
AL type cardiac amyloidosis	Caused by deposition of excessive misfolded light chain immunoglobulin associated with multiple myeloma, Waldenstrom macroglobulinemia, and plasma cell dyscrasias; involves heart, liver, kidney, and peripheral nerves
Wild type TTR related cardiac amyloidosis	Caused by age-related misfolded transthyretin protein deposition; has a slow onset of symptoms
Mutated TTR related cardiac amyloidosis	Often autosomal-dominantly inherited; mutation of TTR protein leads to misfolding of protein resulting in amyloid deposition
AA-Type cardiac amyloidosis	Secondary to systemic inflammatory disorders e.g., Rheumatologic disease and chronic infections; rare heart involvement
Atrial natriuretic peptide (AANP)	Localized in atrium; increased risk of atrial fibrillation due to atrial dilation
APO-A1 related cardiac amyloidosis	Secondary to mutated ApoA-1 lipoprotein; primarily involves kidney, and rarely, heart

TTR: Transthyretin, APO-A1: Apolipoprotein A1

Table 2. Diagnostic Modalities for AL-type Cardiac Amyloidosis [6,10]

Diagnostic modality	Sensitivity, specificity (Percentages)	Findings consistent with cardiac amyloid
EKG	90%, 90%	Diffuse low voltage QRS (<5 mm height), QRS deviation, LBBBs, pseudo–infarction
Echocardiography with strain imaging	90–95%, 80-85%	Biventricular hypertrophy, inter-ventricular septal hypertrophy, bi-atrial dilation, decreased longitudinal strain in mid and basal wall with relative sparing of apical function
Cardiac MRI	80%, 94%	Global transmural or subendocardial late gadolinium enhancement, expansion of ECV leading to enhanced T1 mapping
Nuclear Scintigraphy (Positron Emission Tomography – PET, Technetium labelled imaging)	95%, 98%	Characteristic enhancement due to binding of radiotracer to amyloid
Histopathology	100% sensitivity for endomyocardial biopsy, Tissue biopsy has sensitivity of 75% and specificity of 92%	Fat pad biopsy, Endomyocardial biopsy with immunohistochemical staining showing extracellular deposits of AL amyloid with Congo red stain showing apple-green birefringence under polarized microscopy

MRI: Magnetic resonance imaging, LBBB: Left bundle branch block, ECV: Extracellular volume, PET: Positron emission tomography

Table 3. Summarizing the currently available chemotherapy agents and their mechanisms of action for plasma cell dyscrasias [11]

Class of drug	Mechanism of action
Steroid	Decreases inflammation resulting from chemotherapy-related cell destruction
Melphalan- immunomodulators	Inhibits DNA and RNA synthesis in both resting and dividing tumor cells
Bortezomib- Proteasome inhibitor	Inhibits proteasome resulting in cell cycle arrest and apoptosis
Lenalidomide, pomalidomide- antineoplastic, antiangiogenic, immunomodulator	Increases T-cell and NK cell-mediated cytotoxicity resulting in cell cycle apoptosis; also decreases proinflammatory cytokines and angiogenesis
Daratumumab-Anti CD38 monoclonal antibody	Targets CD 38 on myeloma cells and results in apoptosis

Figure 4. Summarizing the pharmacological agents for management of complications of AL type cardiac amyloidosis [5,12,13]

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