Tc-99m pyrophosphate scintigraphy (PYP) has unmasked a high community prevalence of wild-type transthyretin cardiac amyloidosis (ATTRwt-CA), which is an increasingly recognized etiology of congestive heart failure (CHF) in the elderly. CHF is a known component of the CHA2DS2-VASc score that predicts thromboembolic risk in atrial fibrillation (AF). However, the impact of ATTRwt-CA on thromboembolic risk in AF is unknown.
We hypothesized that ATTRwt-CA independently predicts thromboembolism in CHF patients with atrial fibrillation.
We studied patients with underlying CHF who underwent PYP between 6/2015 and 6/2019. Positive PYP was defined as Perugini grade ≥2 along with heart-to-contralateral lung ratio of ≥ 1.5 on planar image, and diffuse myocardial tracer uptake on the SPECT. Those with positive PYP, negative serum studies for AL amyloidosis and no transthyretin gene mutation were diagnosed with ATTRwt-CA. We compared the prevalence of AF in patients with and without ATTRwt-CA and the incidence of thromboembolism (stroke, transient ischemic attack or systemic embolism) in AF patients with ATTRwt-CA (AF-ATTR) and without (AF-controls).
Of 277 patients referred for PYP, 77 (28%) had ATTRwt-CA. The prevalence of AF was markedly higher in patients with ATTRwt-CA (n=68, 88%) compared to patients with negative PYP (n=77, 39%, p< 0.01). Compared to AF-controls, AF-ATTR patients had similar age (79±7 vs. 79±8 years, p=0.9) and anticoagulation status (96% vs 94%, p=0.58), lower CHA2DS2-VASc Score(4.7±1.4 vs. 5.4±1.2, p=0.001), thicker interventricular septum (1.67 ± 0.27 vs 1.50 ± 0.15 cm, p<0.001) and lower left atrial indexed volume (LAVI) (46±17 vs. 61±35 ml/m2, p=0.003). Despite a lower CHA2DS2-VASc Score, the incidence of thromboembolism was higher in AF-ATTR compared to AF-controls (36.8% vs. 19.5%, p=0.02; OR 2.46, 95% CI 1.16-5.21, p=0.02). On multivariable logistic regression analysis adjusting for CHA2DS2-VASc Score, interventricular septal thickness and LAVI, ATTRwt-CA was an independent predictor of thromboembolism (OR 6.6, 95% CI 2.23-19.69, p<0.001). The incidence of hemorrhagic stroke (p=0.3), intracranial hemorrhage (p=0.9), major bleeding (p=0.7), and all-cause death (p=0.4) did not differ between the 2 groups.
ATTRwt-CA is a strong predictor of thromboembolism in patients with AF, independent of CHA2DS2-VASc score, septal thickness or left atrial size.
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