Is Cardiac Amyloidosis Progressive?
Yes, cardiac amyloidosis is definitively a progressive disease that worsens over time, with the rate of progression and prognosis varying significantly by amyloid type. 1
Natural History and Disease Progression
Cardiac amyloidosis follows a characteristic progressive pattern from early diastolic dysfunction to advanced systolic failure:
- In early stages, amyloid deposits in the myocardial interstitium cause increased myocardial stiffness, leading to impaired diastolic function with initially preserved systolic function 1
- The heart typically maintains normal size with normal systolic function during these earlier stages 1
- With disease progression, systolic dysfunction inevitably develops as amyloid deposits directly cause myocyte necrosis through oxidative stress 1
- The disease exerts detrimental effects on myocardial performance over the course of many months or years 1
Prognosis by Amyloid Type
The rate of progression and survival varies dramatically depending on the specific amyloid protein involved:
AL (Light Chain) Amyloidosis
- Median survival is approximately 13 months, but decreases drastically to only 4 months once heart failure symptoms develop 1
- This represents the most aggressive form with the worst prognosis 1
Hereditary ATTR Amyloidosis
- Median survival is 70 months with variable cardiac involvement 1
Senile (Wild-Type) ATTR Amyloidosis
- Median survival is 75 months with common cardiac involvement 1
Important Clinical Caveat
With rare exceptions, the great majority of restrictive cardiomyopathies including cardiac amyloidosis are progressive and associated with poor prognosis, with 50% survival at 5 years after diagnosis 1
The only exceptions where progression can be halted or reversed include:
- Some cases of iron overload cardiomyopathy following iron chelation therapy 1
- Control of some cases of cardiac amyloidosis with stem cell transplantation and/or chemotherapy 1
Mechanisms of Progressive Deterioration
Multiple pathophysiologic mechanisms drive the relentless progression:
- Continuous amyloid protein deposition in the myocardial interstitium disrupts myocyte function 1
- Direct myocyte necrosis from oxidative stress caused by amyloid deposits 1
- Deposits in the conduction tissue progressively affect electrical conduction 1
- Amyloid deposition in coronary arteries can result in cardiac ischemia 1
- Elevated filling pressures lead to atrial dilation and mechanical dysfunction, even in sinus rhythm 1
Clinical Implications
The progressive nature of cardiac amyloidosis makes early diagnosis and treatment initiation critical, as disease-modifying therapies are much more effective before significant end-organ amyloid deposition has occurred 2