Can amyloidosis present with grade 3 diastolic dysfunction?

Cardiac Amyloidosis Can Present with Grade 3 Diastolic Dysfunction

Yes, cardiac amyloidosis can present with grade 3 diastolic dysfunction, particularly in later stages of the disease when left ventricular relaxation is impaired along with markedly elevated left ventricular filling pressures. 1

Progression of Diastolic Dysfunction in Cardiac Amyloidosis

• In early stages, cardiac amyloidosis typically presents with grade 1 diastolic dysfunction (impaired relaxation pattern) with normal left ventricular filling pressures 1
• As the disease progresses, it advances to grade 2 diastolic dysfunction (pseudonormalization) 1
• In later stages, grade 3 diastolic dysfunction develops, characterized by restrictive filling pattern and abnormally reduced mitral annular e' velocity 1

Echocardiographic Features of Grade 3 Diastolic Dysfunction in Cardiac Amyloidosis

Advanced stages of cardiac amyloidosis with grade 3 diastolic dysfunction show:

• Typical restrictive physiology with a dip and plateau pattern for early diastolic LV pressure changes 1
• Mitral inflow E/A ratio > 2.5 1
• Deceleration time (DT) of E velocity < 150 msec 1
• Isovolumic relaxation time (IVRT) < 50 msec 1
• Decreased septal and lateral e' velocities (3-4 cm/sec) 1
• Higher lateral e' compared with septal e' velocity (unlike constrictive pericarditis) 1
• E/e' ratio > 14 1
• Markedly increased left atrial volume index (>50 mL/m2) 1

Pathophysiology of Diastolic Dysfunction in Cardiac Amyloidosis

• Amyloid deposits in the myocardial interstitium disrupt myocyte function, leading to increased myocardial stiffness and impaired relaxation 1, 2
• The infiltration causes increased ventricular wall thickness with reduced chamber size, resulting in restrictive physiology 2
• Circulating monoclonal light chains in AL amyloidosis may directly impair cardiac function, particularly diastolic relaxation, independent of fibril deposition 3
• The progressive amyloid infiltration leads to worsening diastolic compliance and eventually to systolic dysfunction in advanced stages 2, 4

Clinical Implications of Grade 3 Diastolic Dysfunction

• Grade 3 diastolic dysfunction is associated with poor outcomes in patients with restrictive cardiomyopathy, including cardiac amyloidosis 1
• Median survival in AL amyloidosis is approximately 13 months but decreases dramatically to 4 months with the onset of heart failure symptoms 1, 2
• The presence of restrictive filling pattern (grade 3 diastolic dysfunction) indicates advanced disease with markedly elevated left ventricular filling pressures 1, 4
• Patients with grade 3 diastolic dysfunction due to cardiac amyloidosis may be exceptionally sensitive to negative inotropic medications like calcium channel blockers 5

Diagnostic Considerations

• Strain imaging shows characteristic patterns in cardiac amyloidosis with reduced longitudinal and radial strain, with circumferential strain preserved until severe diastolic dysfunction (restrictive filling) develops 6
• Parameterized diastolic filling analysis reveals greater peak resistive force in cardiac amyloidosis patients compared to controls, consistent with severe diastolic dysfunction 7
• The presence of grade 3 diastolic dysfunction with preserved ejection fraction should raise suspicion for infiltrative cardiomyopathies like amyloidosis 2
• It's important to distinguish between restrictive LV filling pattern (which can occur in various diseases) and true restrictive cardiomyopathy due to amyloidosis 1

Pitfalls and Caveats

• Not all patients with cardiac amyloidosis will present with grade 3 diastolic dysfunction; the severity depends on the disease stage 1, 2
• Calcium channel blockers should be avoided in patients with cardiac amyloidosis as they can precipitate severe systolic dysfunction due to their negative inotropic effects 5
• Echocardiographic assessment alone cannot differentiate between types of amyloidosis (AL vs. TTR); additional testing is required 2
• The presence of normal annular e' velocity in a patient with heart failure should raise suspicion of pericardial constriction rather than amyloidosis 1