USA: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a type of heart failure with preserved ejection fraction (HFpEF). ATTR-CM can be diagnosed with the help of technetium Tc 99m pyrophosphate scintigraphy (PYP). There is no clarity on which HFpEF patients have sufficient risk of ATTR-CM to warrant PYP.
Based on the above, in a recent study, researchers from the US aimed to derive and validate a simple ATTR-CM score for predicting increased ATTR-CM risk in HFpEF patients. The study, published in JAMA Cardiology, found a simple 6-variable clinical score useful for guiding PYP use and increasing ATTR-CM recognition in patients with HFpEF.
Daniel R. Davies, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, and colleagues conducted a retrospective cohort study. It included 666 patients with HF (ejection fraction ≥ 40%) and suspected ATTR-CM referred for PYP at Mayo Clinic, Rochester, Minnesota, from May 10, 2013, through August 31, 2020.
Data analysis was done from September 2020 through December 2020. A logistic regression model that predicted ATTR-CM was derived and translated to a point-based ATTR-CM risk score. Further validation of the score was done in a community ATTR-CM epidemiology study of older HFpEF patients with increased left ventricular wall thickness ([WT] ≥ 12 mm) and in an external (Northwestern University, Chicago, Illinois) HFpEF cohort referred for PYP.
Self-reporting of the race was done by all the participants. Both case and control patients were discovered by specialist evaluation and PYP scanning.
The study's main outcome was the performance of the derived ATTR-CM score in all cohorts (community validation, referral validation, and external validation) and a high-risk ATTR-CM score prevalence in 4 multinational HFpEF clinical trials.
The key findings of the study were as follows:
Participant cohorts included were referral derivation (n = 416; ATTR-CM prevalence = 45%), referral validation (n = 250; ATTR-CM prevalence = 48%), community validation (n = 286; ATTR-CM prevalence = 6%), and external validation (n = 66; ATTR-CM prevalence = 39%).
Score variables included age, male sex, hypertension diagnosis, relative WT more than 0.57, posterior WT of 12 mm or more, and ejection fraction less than 60% (score range −1 to 10).
Discrimination (area under the receiver operating characteristic curve [AUC] 0.89) and calibration (Hosmer-Lemeshow; χ2 = 4.6) were strong.
Discrimination (AUC ≥ 0.84) and calibration (Hosmer-Lemeshow χ2 = 2.8; Hosmer-Lemeshow χ2 = 4.4; Hosmer-Lemeshow χ2 = 2.5 in referral, community, and external validation cohorts, respectively) were maintained in all validation cohorts.
Precision-recall curves and predictive value vs. prevalence plots indicated clinically useful classification performance for a score of 6 or more (positive predictive value ≥25%) in clinically relevant ATTR-CM prevalence (≥10% of patients with HFpEF) scenarios.
In the HFpEF clinical trials, 11% to 35% of male and 0% to 6% of female patients had a high-risk (≥6) ATTR-CM score.
"A simple, 6-variable clinical score may help identify patients with suspected HFpEF who are at increased ATTR-CM risk and should undergo an additional clinical evaluation to identify or exclude ATTR-CM," the researchers wrote.
"ATTR-CM is a form of HFpEF with a specific etiology that is underrecognized and has specific and highly effective therapy. Further validation is needed for this score," they conclude.
Reference:
Davies DR, Redfield MM, Scott CG, et al. A Simple Score to Identify Increased Risk of Transthyretin Amyloid Cardiomyopathy in Heart Failure With Preserved Ejection Fraction. JAMA Cardiol. Published online September 07, 2022. doi:10.1001/jamacardio.2022.1781