An echo score raises the suspicion of cardiac amyloidosis in Chinese with heart failure with preserved ejection fraction

Abstract

Aims: Transthyretin cardiac amyloidosis (ATTR-CA) has been realized as an important cause of heart failure with preserved ejection fraction (HFpEF). We aim to provide insights into its prevalence in Chinese HFpEF patients, which is not known to date, using increased wall thickness (IWT) score by echocardiography.

Methods: Consecutive patients with HFpEF (EF ≥ 40%) and IWT (≥12 mm) were prospectively screened. Echocardiography was performed, and the IWT score incorporated relative wall thickness, E/e' ratio, longitudinal strains, and tricuspid annular plane systolic excursion, and septal apical-to-base ratio was calculated. ATTR-CA was defined as score ≥8 in the absence of serum and urine free light chain.

Results: Six hundred twenty-four HFpEF patients from January 2019 to December 2021 were enrolled, of which 65.2% were males and the median (interquartile range [IQR]) age was 66 (IQR 57, 73) years. Thirty-three patients (5.3%, 95% CI 3.5-7.0%) were with score ≥8, and 33.3% were females. They were younger (58 vs. 69 years, P < 0.001), had higher NT-proBNP (6525.0 vs. 1741.5 pg/mL, P < 0.001) and troponin I (105.2 vs. 27.7 pg/mL, P = 0.001) level, and lower LVEF (47% vs. 57%, P < 0.001) compared with the patients with score <5. In the internal cohort (82 patients) who had undergone scintigraphy, the IWT score ≥8 was shown to have a sensitivity of 85.7% (95% CI 56.2-97.5%) and a specificity of 92.6% (95% CI 83.0-97.3%) for diagnosing CA, and the IWT score <5 had great accuracy in excluding CA with the negative predictive value of 100%, supporting the clinical usefulness of the IWT score to guide further dedicated testing for ATTR-CA.

Conclusions: The IWT score by echocardiography was an excellent tool for screening ATTR-CA in HFpEF. In Chinese HFpEF patients associated with a hypertrophic phenotype, the proportion of highly suspected ATTR-CA as detected by IWT score ≥8 was 5.3%, lower than the reported prevalence of ATTR-CA in non-Asian patients with the disease.

Keywords: 99mTc-pyrophosphate scintigraphy; Heart failure with preserved ejection fraction; Multi-parametric echocardiography score; Transthyretin amyloid cardiomyopathy.

Figure 1

Flow chart for study design, patient inclusion, and group classification by the IWT score.

Figure 2

The validation cohort that was consisted of 82 patients who underwent scintigraphy and the patients' classification by the IWT score and the result of scintigraphy.

Figure 3

A HFpEF patients with the IWT score = 9 and a positive ^99mTc‐PYP scintigraphy. (A) ^99mTc‐PYP SPECT and (B) ^99mTc‐PYP SPECT/CT (grade 3 radiotracer uptake on the Perugini scale at 1 and 3 h and 1‐h heart‐to‐lung ratio of 1.72 and 3 h of 1.77). (C) A “bull's‐eye” presentation of LV longitudinal strains by TTE showing typical apical sparing pattern and low longitudinal strains (3.2%). (D) Doppler was restrictive with the E/e′ ratio of 35.07. (E) TTE (four‐chamber view) showed left ventricular hypertrophy. (F) ECG presented atrial fibrillation and pacemaker rhythm. CT, computed tomography.