Simple score developed to predict increased risk of transthyretin amyloid cardiomyopathy in heart failure patients with preserved ejection fraction

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1. Simple score composed of 3 clinical variables (age, male gender, diagnosis of hypertension) and 3 echocardiographic variables (ejection factor, posterior wall thickness, relative wall thickness) predicts an increased risk of cardiomyopathy transthyretin amyloid in heart failure patients with preserved ejection fraction.

2. Clinically useful classification performance was scored for a score of 6 or greater in clinically relevant prevalence scenarios of transthyretin amyloid cardiomyopathy.

Level of evidence assessment: 2 (good)

Summary of the study: Amyloid transthyretin cardiomyopathy (ATTR-CM) is characterized by left ventricular (LV) wall thickening and manifests as clinical heart failure, usually with preserved ejection fraction. Heart failure with preserved ejection fraction (HFpEF) often affects older people with existing hypertensive heart disease and LV wall thickening due to hypertrophy, and studies suggest a prevalence of ATTR-CM between 6 and 13% in this patient population. The objective of this retrospective cohort study was to derive and validate a simple score to predict an increased risk of ATTR-CM in patients living with HFpEF (ejection fraction ³ 40%). A total of 666 patients with HFpEF referred to Mayo Clinic between May 2013 and August 2020 were included. The primary outcomes were the ATTR-CM score performance in all cohorts and the prevalence of the high-risk ATTR-CM score in 4 multinational HFpEF clinical trials. The score range was -1 to 10, and variables included clinical factors such as age, male sex, and diagnosis of hypertension, in addition to echocardiographic factors such as relative wall thickness ( WT) greater than 0.57, posterior WT ³ 12 mm and ejection fraction.

Click to read the study in JAMA Cardiology

Relevant reading: Prevalence of transthyretin amyloid cardiomyopathy in heart failure with preserved ejection fraction

In depth [retrospective cohort]: A total of 666 patients were included in this study [median age 76; 333 [80%] males, and 380 [94%] were white). The median ejection fraction (EF) of the patients included was 56% (IQR, 50%-63%). The participant cohorts included were baseline derivation (n=416), baseline validation (n=250), community validation (n=286) and external validation (n=66). Variables considered in the simple score included: age, male sex, diagnosis of hypertension, ejection fraction 2 = 4.6; P = 0.46) were found to be strong. Discrimination (AUC ³ 0.84; P 2 = 2.8; P=0.84; Hosmer-Lemeshow 𝑥2 = 4.4; P=0.35; Hosmer-Lemeshow 𝑥2 = 2.5; P = 0.78 in reference, community and external validation cohorts, respectively) were maintained in all validation cohorts. Moreover, the model-based probabilities closely matched the observed prevalence for each of the given score values ​​(goodness of fit 𝑥2 = 4.6; P = 0.46), indicating a robust calibration. Clinically useful classification performance for a score of 6 or greater in the clinically relevant ATTR-CM was indicated. Using 6 as the high risk threshold had a sensitivity of 93% and a specificity of 62%.

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