Features of atrial fibrillation in wild-type transthyretin cardiac amyloidosis: a systematic review and clinical experience

Abstract

Aims: Wild-type transthyretin (ATTRwt) cardiac amyloidosis has emerged as an important cause of heart failure in the elderly. Atrial fibrillation (AF) commonly affects older adults with heart failure and is associated with reduced survival, but its role in ATTRwt is unclear. We sought to explore the clinical impact of AF in ATTRwt.

Methods and results: Patients with biopsy-proven ATTRwt cardiac amyloidosis (n = 146) were retrospectively identified, and clinical, echocardiographic, and biochemical data were collected. Patients were classified as AF or non-AF and followed for survival for a median of 41.4 ± 27.1 months. Means testing, univariable, and multivariable regression models were employed. A systematic review was performed. AF was observed in 70% (n = 102). Mean age was similar (AF, 75 ± 6 vs. non-AF, 74 ± 5 years, P = 0.22). Anticoagulant treatment of patients with AF was as follows: 78% warfarin, 17% novel anticoagulant, and 6% no anticoagulation. Amiodarone was prescribed to 24%. There were no differences in left ventricular ejection fraction (P = 0.09) or left atrial volume (P = 0.87); however, mean diastolic dysfunction grade was higher in AF (mean 2.7 ± 0.5 vs. 2.4 ± 0.5, P = 0.01). While creatinine (P = 0.52) and B-type natriuretic peptide (P = 0.48) were similar, patients with AF had lower serum transthyretin concentrations (221 ± 51 vs. 250 ± 52 μg/mL, P < 0.01). Survival between groups was similar (P = 0.46).

Conclusions: These data provide an evidence basis for clinical management and demonstrate that AF in ATTRwt does not negatively impact survival. Further analysis of the relationship between transthyretin concentration and AF development is warranted.

Keywords: Atrial fibrillation; Cardiac amyloidosis; Transthyretin.

Figure 1

Kaplan–Meier analysis of age‐adjusted survival stratified based on presence of atrial fibrillation (AF) in wild‐type transthyretin amyloidosis. There is no significant difference in survival in patients with paroxysmal AF (hazard ratio 1.04, P = 0.89) or permanent AF (hazard ratio 1.37, P = 0.29) as compared with those who do not have AF.

Figure 2

(A) Box and whisker plots demonstrating serum transthyretin (TTR or prealbumin) levels stratified by the presence and type of atrial fibrillation (AF) in wild‐type transthyretin amyloidosis. Note that serum TTR concentrations are lower in permanent or longstanding AF vs. paroxysmal or no AF, P = 0.0002. (B) Survival in patients with atrial fibrillation (AF), stratified by TTR (TTR or prealbumin) concentration that is above or below 180 μg/dL in ATTR wild‐type amyloidosis. Hazard ratio is 2.00 (P = 0.059).

Figure 3

Survival in patients with atrial fibrillation stratified by the use of antiarrhythmic medications. There is no significant difference in survival among those patients who were treated with a rhythm or rate control strategy (hazard ratio 1.70, P = 0.08).