Longitudinal changes in PYP heart-to-contralateral lung ratio and echocardiographic diastolic parameters in ATTR cardiac amyloidosis treated with tafamidis
R Gabarin, S Martin, M Patel, S Mahendran, S De, S Saveski, S Smith, R DaveyAbstract
Background
Transthyretin cardiac amyloidosis (ATTR-CA) is characterized by misfolding and deposition of a liver-produced protein in cardiac muscle. Technetium-99m pyrophosphate scintigraphy (PYP scans) demonstrate myocardial radiotracer uptake associated with ATTR-CA, quantified by heart-to-contralateral lung (H/CL) ratios. Evidence suggests H/CL ratio can decrease over time with tafamidis, a transthyretin stabilizer. It remains unclear whether changes in H/CL ratio correspond with improvement in echocardiographic (echo) diastolic function.
Purpose
To assess treatment response to tafamidis in terms of changes in H/CL ratio and echo parameters (LV septal and posterior wall thickness, LVEF, LA volume index, E/e’, medial e’) in patients with ATTR-CA.
Methods
This is a retrospective observational study of patients with ATTR-CA on tafamidis therapy who underwent baseline and follow-up imaging, either PYP scan or echo, from 2017 to 2025. Primary outcomes were changes in H/CL ratio and echo parameters. ANCOVA was used to fit a linear regression model to predict final imaging values with three parameters: baseline imaging value, age of onset of ATTR-CA, and time on tafamidis. When PYP scans and echo were performed within three months of each other, patients were included in a Spearman correlation analysis.
Results
64 consecutive patients included, two having hereditary ATTR-CA and the rest having wild type. 39 patients had follow up PYP scans and 47 had follow up echos. Mean age was 83.0 ± 6.8 SD years. At baseline, 45.3% (29) were NYHA II and 35.9% (23) were NYHA I. Median [IQR] follow up duration was 19.6 months [10.9–28.4] for PYP scans and 23.9 months [13.0–34.8] for echo. Mean H/CL ratio was 1.86 ± 0.35 at baseline and 1.54 ± 0.23 at follow up. With ANCOVA, H/CL ratio decreased by -0.0051 per month (CI: -0.0098, -0.0005) (p =0.032). Baseline H/CL ratio was significantly associated with follow up H/CL ratio (β=0.4032, p <0.001), whereas age of onset did not have an effect (p =0.4). Duration of tafamidis therapy and age of onset did not have a significant effect on LV septal and posterior wall thickness, LVEF, LA volume index, E/e’, or medial e’. Baseline echo values were significantly associated with follow up values. In a Spearman correlation analysis, initial H/CL ratio was correlated with both baseline LV posterior wall (n=30, ρ=0.38, p value=0.035) and septal wall diameter (n=30, ρ=0.48, p value=0.007). Follow-up H/CL ratio did not correlate with any follow up echo variables including LV posterior wall (n=20, p value=0.8).and septal wall diameter (n=20, p value = 0.85).
Conclusions
In our cohort, H/CL ratio decreased over time with tafamidis but echo parameters remained stable. This suggests tafamidis maintains stability rather than changes in heart structure and diastolic function over a two year follow up period. PYP-SPECT may be a poor predictor for myocardial function in patients with ATTR-CA but more research is necessary.Cohort Characteristics and ImagingFor image description, please refer to the figure legend and surrounding text.Predicted Changes in Imaging GraphsFor image description, please refer to the figure legend and surrounding text.