Subtype-Specific Interactions and Prognosis in Cardiac Amyloidosis

Abstract

Background: Light chain (AL) and transthyretin (ATTR) amyloidosis have a similar effect on myocardial function but very different disease trajectories and survival. However, limited data are available evaluating subtype-specific predictors of outcomes in a large contemporary cohort.

Methods and results: We retrospectively investigated 360 patients at the time of initial diagnosis of cardiac amyloidosis (191 AL and 169 ATTR) from 2002 to 2014. Clinical, laboratory, electrical, and morphologic covariates were evaluated based upon amyloid subtype. ATTR etiology was associated with older age, more chronic medical conditions, and the use of standard heart failure medical therapy. Left ventricular mass index and electrocardiographic voltage were higher in ATTR, while there was no difference in ejection fraction or markers of diastology between subtypes. A multivariable Cox model was generated using previously identified predictors of negative outcomes in cardiac amyloidosis and analyzed after stratification for subsequent amyloid-specific treatment. An AL etiology was the most predictive variable (hazard ratio 3.143, P<0.001) of 3-year all-cause mortality. The only covariate that showed a significantly greater magnitude of effect on mortality in 1 amyloid subtype versus the other was amyloid-specific treatment in AL (P=0.015). The magnitude of effect of other variables on mortality did not significantly differ between subtypes.

Conclusions: Clinical, morphological, electrical, and biomarker data do not significantly interact with amyloid subtype in its association with mortality, despite the fact that the prognosis in each subtype differs greatly. This suggests an additional factor or factors (such as light chain toxicity) contributing to poorer outcomes in AL amyloid.

Keywords: amyloid; cardiomyopathy; echocardiography; electrocardiography; prognosis.

Figure 1

CONSORT flow chart detailing study population. AL indicates immunoglobulin light chains; ATTR, transthyretin; CONSORT, Consolidated Standards of Reporting Trials.

Figure 2

Diagnostic method for inclusion of 360 total patients. CMR, cardiac magnetic resonance imaging; (99m)Tc‐PYP, technetium‐99m‐pyrophosphate.

Figure 3

Kaplan–Meier survival curves by amyloid subtype. A, Survival curves by amyloid subtype after adjustment for eGFR, NYHA class ≥III, atrial fibrillation, ejection fraction, LV mass index, deceleration time, and Sokolow voltage index. B, Survival curves stratified by amyloid‐specific treatment. AL indicates immunoglobulin light chains; ATTR, transthyretin; eGFR, estimated glomerular filtration rate; LV, left ventricular; NYHA, New York Heart Association.

Figure 4

Monthly mortality by biomarker tertile for all patients with cardiac amyloidosis. Troponin T: tertile 1 ≤0.04, tertile 2 0.04 to 0.1, tertile 3 ≥0.10. NT‐proBNP: tertile 1 <3075, tertile 2 3075 to 7930, tertile 3 >7930. FLC‐diff: tertile 1 <199.84, tertile 2 199.84 to 561.88, tertile 3 >561.88. FLC‐diff, free light chain difference; NT‐proBNP, N‐terminal prohormone of brain natriuretic peptide.