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Medically reviewed by Dr. Shani S. Saks, D.O. on July 27, 2023

This study found that patients with higher transthyretin amyloid cardiomyopathy scores had different clinical and echocardiographic characteristics and higher cardiovascular risk. Heart failure patients with preserved ejection fraction may benefit from the transthyretin amyloid cardiomyopathy score’s moderate discriminatory performance and satisfactory calibration in predicting outcomes.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a common but underdiagnosed cause of heart failure with preserved ejection fraction (HFpEF). Despite the high potential burden of ATTR-CM in HFpEF, there is still little evidence regarding the association of ATTR-CM burden with adverse outcomes in patients with HFpEF. 

A study in the European Journal of Clinical Investigation has assessed the ATTR-CM burden in the HFpEF population through a simple score and the association of the score with clinical outcomes in this population.

Study Population

In this multicentre, international, randomized controlled trial, data from 870 patients enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial were analyzed.

ATTR-CM Score and Patient Characteristics

In this study, an ATTR-CM score of 6 components was evaluated to assess risk of ATTR-CM.  These 6 components were age (60–69 years, 2 points; 70–79 years, 3 points; greater or equal to 80 years, 4 points); sex (male, 2 points); hypertension diagnosis (present, -1 point), LVEF (<60%, 1 point), posterior wall thickness (12 mm or greater, 1 point); and relative wall thickness (0.57, 2 points). There were 165 (18.9%) patients who had  an ATTR-CM score ≥6, representing a potentially high burden of ATTR-CM risk. Compared with patients with an ATTR-CM score <6, those with a score ≥6 were older, predominantly male, and had lower blood pressure, body mass index, left ventricular ejection fraction, and estimated glomerular filtration rate.

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Clinical Characteristics of Patients With ATTR-CM Scores ≥6

Moreover, those with a score ≥6 displayed a lower prevalence of hypertension but a higher prevalence of atrial fibrillation and coronary artery disease and were treated more often with diuretics and warfarin.

Baseline Echocardiographic Characteristics of Patients with ATTR-CM Scores ≥6

Regarding the baseline echocardiographic characteristics, patients with ATTR-CM scores ≥6 had a thicker posterior wall and interventricular septum, increased relative wall thickness, increased left atrial volume, and a higher prevalence of concentric hypertrophy than those with a score <6.

Association of ATTR-CM Score With Clinical Outcomes

The study showed a statistically significant association per one increment in the ATTR-CM score with increased risks of both the primary (cardiovascular death, aborted cardiac arrest, or HF hospitalization during the follow-up period) and secondary outcomes (all-cause mortality, cardiovascular death, HF hospitalization, and any hospitalization), except stroke. Additionally, the primary and secondary outcomes were significantly greater in patients with an ATTR-CM score ≥6 than those with a score <6. No beneficial therapeutic effects of spironolactone were observed in patients in either ATTR-CM score strata.

Performance of the ATTR-CM Score

The ATTR-CM score showed moderate discriminatory performances in predicting the primary and secondary outcomes and good calibration between the predicted and observed 5-year event rates.


Ye, M., Liu, X., Gu, Z., Sun, J., Dong, Y., Chen, Y., Liu, C., Wu, Z., & Zhu, W. (2023). A simple ATTR-CM score to identify transthyretin amyloid cardiomyopathy burden in HFpEF patients. European Journal of Clinical Investigation, e14045. Advance online publication. https://doi.org/10.1111/eci.14045