Transthyretin amyloid cardiomyopathy among patients with heart failure and preserved ejection fraction: the AMY score.

Abstract

Transthyretin 'wild-type' amyloid cardiomyopathy (ATTRwt-CM) is a differential diagnosis of heart failure with preserved ejection fraction (HFpEF). The clinical work-up for ATTRwt-CM is challenging. Considering a combination of clinical variables specific for ATTRwt-CM might aid in identifying patients at risk. Sixty patients (78±6years, 8% female) were diagnosed with ATTRwt-CM by endomyocardial biopsy. Preserved ejection fraction (LVEF >45%) was present in 41 of the patients. Those were 1:1 propensity score age- and sex-matched to a cohort of patients with HFpEF. ATTRwt-CM patients had less obesity (P=0.01) and higher septal thickness (IVSd, P<0.01) as well as more diastolic dysfunction (E/e', P<0.01). On multivariable regression IVSd>14mm, E/e'>14 and absence of obesity (P>0.01 for all) were identified as predictors for ATTRwt-CM. A weighted point-based score was derived with IVSd>14mm=1 point; absence of obesity=2 points; and E/e'>14=3 points. Area under the curve (AUC) for the summation score was 0.91 (0.84-0.97, P<0.01) and a score of more than 3 points predicted ATTRwt-CM with good sensitivity (78%) and specificity (90%). The score was validated in an external cohort of 142 patients with ATTRwt-CM and 419 HFpEF patients showing sufficient accuracy (AUC 0.91, 0.88-0.94, P<0.01). A value greater than 3 points demonstrated a high sensitivity (93%) and a negative predictive value of 97%. A score based on basic clinical and echocardiographic features helps to distinguish ATTRwt-CM from typical HFpEF. This could facilitate the diagnostic work-up for these patients and enable earlier disease screening on a large scale.