Thromboembolic complications common in ATTR-CM
Systemic embolism in amyloid transthyretin cardiomyopathy
Introduction and methods
Transthyretin cardiac amyloidosis (ATTR-CM) is a progressive, often fatal form of cardiac disease characterized by precipitation of the protein transthyretin in the heart. There is both an inherited form (ATTRv) and an acquired form (ATTRwt) . Atrial arrhythmias and thromboembolic complications, such as intracardiac thrombosis, may be the first manifestation of ATTR-CM [2-4], but data on the incidence and prevalence of these complications are scarce. Moreover, there is an urgent need to better predict and prevent thromboembolic complications in these patients.
Aim of the study
The aim of this study was to determine the incidence and prevalence of thromboembolic complications in patients with ATTR-CM and to investigate the factors associated with these complications. The predictive value of the CHA2DS2-VASc score in patients with ATTR-CM was also examined, as well as the incidence of thromboembolic complications in patients with or without AF according to (type of) oral anticoagulation (OAC).
The researchers used longitudinally collected data from 1191 patients with ATTR-CM (87% male; median age: 77.1 years; 83% ATTRwt) from 4 referral amyloid centers in Italy, Spain, the UK and the US. The diagnosis of ATTR-CM was established in the presence of transthyretin deposits in an endomyocardial biopsy or extracardiac biopsy with an additional finding. In addition, the diagnosis of ATTR-CM could be made if, in addition to findings on scintigraphy, abnormalities were found on echocardiogram or cardiac magnetic resonance (CMR) suggestive of amyloidosis in the absence of monoclonal antibodies. Genetic testing for possible mutations in the TTR gene was performed in all patients. Patients who had visited a referral center at least 2 times and whose data were available from at least 80 of the 100 prespecified variables were included.
The researchers determined the incidence and prevalence of thromboembolic complications, such as stroke, TIA, or peripheral embolism, in patients with ATTR-CM.
Total study population
- A total of 162 (13.6%) patients had already experienced a thromboembolic complication at initial evaluation at participating centers.
- After a median follow-up of 19.9 months (IQR: 9.9-35.5), a thromboembolic complication had occurred in 41 (3.4%) patients, of whom 24 patients had AF at initial evaluation, 10 patients developed AF during follow-up, and 7 patients did not have AF at initial evaluation nor developed AF during follow-up.
- Total prevalence of thromboembolic complications at initial evaluation and during follow-up was 16.2%.
- Factors associated with thromboembolic complication during follow-up were: age (HR: 1.07; 95%CI: 1.02-1.12; P=0.002), African-American race (HR: 5.41; 95%CI: 2.75-10.64; P <0.001) and peripheral vascular disease (PVD) (HR: 2.48; 95%CI: 1.30-4.75; P <0.006).
Patients without AF
- 566 Patients had no history of AF at initial evaluation, but 73 patients (30.6%) developed AF during follow-up.
- The incidence of thromboembolic complications was 0 per 100 patient-years in patients without AF who received OAC, and 1.3 per 100 patient-years in patients without AF who did not receive OAC.
- The CHA2DS2VASc score did not predict thromboembolic complications in patients without AF.
Patients with AF
- 625 Patients had history of AF at initial evaluation; 558 (89.3%) received OAC, 40 (6.4%) received OAC during part of follow-up and 27 (4.3%) received no OAC.
- The incidence of thromboembolic complications was 1.7 per 100 patient-years in patients with AF receiving OAC, and 4.8 per 100 patient-years in patients with AF not receiving OAC
- Thromboembolic complications occurred only in patients with AF and a CHA2DS2VASc score ≥3. In a small subgroup of patients with AF who did not receive OAC, thromboembolic complications occurred only in those with a CHA2DS2VASc score ≥4.
- There was no difference in the incidence of thromboembolic complications between patients with AF treated with VKA or DOAC (P=0.66).
The prevalence of thromboembolic complications in patients with ATTR-CM was 16.2%. The incidence of thromboembolic complications was lower in patients receiving OAC than in those not receiving OAC. However, the incidence did not differ between patients with AF treated with VKA or DOAC. The CHA2DS2VASc score was a poor predictor of thromboembolic complications and should not be used to assess thromboembolic risk in this population.