What is the prognosis for cardiac amyloidosis?

Cardiac Amyloidosis Prognosis

Cardiac involvement is the single most important prognostic indicator in amyloidosis, with survival heavily dependent on the amyloid subtype and disease stage at diagnosis. 1

Prognosis by Amyloid Subtype

AL Cardiac Amyloidosis (AL-CM)

• Median survival is approximately 13 months from diagnosis without treatment, dropping dramatically to only 4 months once heart failure symptoms develop 2
• Historically, median survival ranged from 6 months with a 6% three-year survival rate 1
• With modern chemotherapy (melphalan and prednisone combinations), median survival improved to 17-18 months compared to 8.5 months with colchicine alone 1
• Patients with cardiac involvement undergoing high-dose melphalan and hematopoietic cell transplantation have a median survival of only 1.6 years, compared to 6.4 years in those without cardiac involvement 1
• Treatment-related mortality remains high at 13% at 100 days, with 42% of deaths being cardiac deaths 1

ATTR Cardiac Amyloidosis (ATTR-CM)

• Hereditary ATTR-CM has a median survival of approximately 70 months 2
• Wild-type (senile) ATTR-CM has the slowest progression with median survival of approximately 75 months 2
• Even in the most severe cohort from staging systems, median survival is roughly 2 years 1
• With tafamidis treatment, cardiovascular mortality and cardiovascular-related hospitalization are reduced 3

AA Cardiac Amyloidosis

• Median survival is approximately 25 months 2
• AA amyloidosis rarely affects the heart, making cardiac involvement less common 1

Key Prognostic Biomarkers

Universal Markers (Both AL-CM and ATTR-CM)

• Troponin and NT-proBNP are the most powerful indicators of disease burden and prognosis 1
• Peak VO2 < 13 mL/kg/min coupled with NT-proBNP ≥ 1,800 ng/L predicts increased all-cause death or heart failure hospitalization 1
• Elevated cardiac troponins (especially troponin T) are independent predictors of mortality, with median survival of 6-8 months in those with detectable levels versus 21-22 months in those with undetectable levels 1

AL-CM Specific Markers

• Difference between involved and uninvolved free light chains (dFLC) 1
• Bone marrow plasmacytosis ≥ 10% independently predicts shorter survival 4
• Symptom onset to diagnosis > 6 months is associated with worse outcomes (HR 1.94) 4

ATTR-CM Specific Markers

• Kidney function, particularly eGFR < 45 mL/min/1.73 m² indicates moderate reduction in survival 1
• Increasing diuretic dose and worse NYHA functional class are independent risk factors for worse survival 1

Clinical Prognostic Factors

Poor Prognosis Indicators

• NYHA functional class III-IV 1
• Systolic blood pressure < 100 mm Hg 1
• 6-minute walk test distance < 200 meters (HR 1.85) 4
• Presence of ventricular couplets on Holter monitoring (affects 57% of patients; 29% have couplets, 18% have NSVT) 1
• Left ventricular wall thickness > 12-15 mm on echocardiography 1
• Grade 3 diastolic dysfunction with restrictive filling pattern 5

Important Caveats

• Staging systems were developed before modern effective therapies (daratumumab for AL, tafamidis for ATTR) became available, so historical survival data may underestimate current prognosis 1
• Reliance on staging systems alone may misidentify patients who are either too well or too sick for advanced heart failure therapies 1
• ECG and imaging parameters have prognostic value that is not well established 1

Treatment Response and Prognosis

AL-CM Treatment Response Timeline

• Hematologic response typically occurs within 3-6 months of treatment initiation 2
• Cardiac response generally occurs 6-12 months after hematologic response 2
• Early hematologic response (within 1 month) significantly impacts survival: very good partial response yields median survival of 47 months, partial response 25 months, and no response only 5 months 4
• Cardiac response at 3 months predicts significantly longer survival (47 vs 11 months) 4
• Bortezomib use is associated with early hematologic and cardiac responses and longer overall survival 4

ATTR-CM Treatment Impact

• Tafamidis reduces cardiovascular mortality and cardiovascular-related hospitalization 3
• Novel therapies targeting TTR gene silencing, tetramer stabilization, and amyloid degradation are in development 6

Advanced Disease and Transplantation

Heart Transplantation Outcomes

• AL-CM cardiac transplantation has a bleak prognosis with 5-year survival of only 20-30% 1
• In one series, 39% were alive at 48 months, with 4 of 10 patients developing amyloid deposition in the cardiac allograft 1
• Survival improves if cardiac transplantation is followed by bone marrow transplantation, reaching 5-year survival of 35-55% 1
• Hereditary ATTR-CM with combined cardiac and liver transplantation achieves 5-year survival of 50-80% 1

Mechanical Circulatory Support

• Left ventricular assist devices (LVADs) are poorly tolerated due to small LV cavity and biventricular involvement 1

Clinical Pitfalls to Avoid

• Do not delay diagnosis: Symptom onset to diagnosis > 6 months independently predicts worse outcomes 4
• Do not rely solely on staging systems: Traditional heart failure markers (peak VO2, NYHA class, blood pressure) are required to identify appropriate candidates for advanced therapies 1
• Do not overlook subtle symptoms: Low-output heart failure symptoms like fatigue and GI symptoms may be nonspecific and attributed to other conditions 1
• Do not use digoxin: It should be avoided in cardiac amyloidosis 1
• Recognize that prognosis varies dramatically by subtype: AL-CM has months of survival without treatment, while ATTR-CM has years 2, 7