Development of a Predictive Tool in Patients With High Pretest Probability for Transthyretin Amyloid Cardiomyopathy

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure, arrhythmias, and valvular disease.

The objectives of the study were to develop: 1) screening criteria to identify high-risk patients for ATTR-CM; and 2) a predictive tool for ATTR-CM diagnosis.

This prospective observational registry (2019-2022) at 2 Vancouver academic sites screened patients aged >60 years presenting to heart failure, atrial fibrillation, transcatheter valve clinics, and cardiologists' offices. Patients meeting high-risk criteria who underwent technetium-99m-pyrophosphate were included. Predictors of ATTR-CM were identified using univariable and multivariable logistic regression.

Of 2,500 patients screened, 200 were enrolled (mean age 78.4 ± 8.3 years; 64.5% male) with a mean follow-up of 3 years. ATTR-CM was diagnosed in 46 (23.0%), and 7 (3.5%) had immunoglobulin light-chain amyloidosis amyloidosis. Compared to non-ATTR-CM, those with ATTR-CM were older (82.6 ± 7.1 years vs 77.2 ± 8.1 years; P < 0.001), male (80.4% vs 59.7%, P = 0.013), and had higher NT-proBNP (3,633 vs 2018; P = 0.027). ATTR-CM patients had greater posterior wall thickness (14.5 ± 3.2 vs 11.2 ± 1.8; P < 0.001), low QRS voltages (37.0% vs 3.9%; P < 0.001), more atrioventricular block (38.5% vs 19.2%; P = 0.018), and higher Doppler E/e' (18.7 ± 7.6 vs 14.4 ± 6.2, P = 0.001). A 5-item predictive tool (score ≥7) identified patients who had positive ATTR-CM diagnoses (sensitivity 89.1% [95% CI: 80.1%-98.1%], specificity 85.1% [95% CI: 70.4%-90.7%], area under receiver operating characteristic curve 0.931 [95% CI: 0.884-0.978]).

Broad screening criteria of high-risk populations referred for technetium-99m-pyrophosphate yielded new ATTR-CM diagnoses in 23% of patients. Our predictive tool may guide clinicians in refining pretest probability and optimizing diagnosis for ATTR-CM. External validation in broader populations is warranted.