Aims : Traditional echocardiographic parameters for the assessment of suspected cardiac amyloidosis (CA) are of limited diagnostic accuracy. We sought to explore differences and the discriminative value of phasic left atrial strain (LAS) reductions and of regional longitudinal left ventricular (LV) strain alterations (relative apical sparing; RELAPS) in CA and other causes of LV wall thickening (LVH). Methods and results : We included 54 patients with unclear LVH (mean septal diastolic wall thickness 17.8 ± 3.5 mm); CA was bioptically confirmed in 35 patients (8 mATTR, 6 wtATTR, 20 AL, and 1 AA amyloidosis) and LVH in 19 subjects. We analysed RELAPS as well as LA reservoir (LASr), conduit (LAScd), and contraction strain (LASct) using 2D speckle tracking echocardiography (EchoPAC software, GE). RELAPS was higher (1.37 ± 0.94 vs. 0.86 ± 0.29, P < 0.007), whereas atrial mechanics were significantly reduced in CA (LASr, LAScd, and LASct: 9.7 ± 5.2%, −6.5 ± 3.5%, and −5.0 ± 4.1% in CA; and 22.7 ± 7.8%, −13.9 ± 5.2%, and −13.0 ± 5.5% in LVH, respectively; P < 0.001 each). With an area under the curve (AUC) of 0.91 [95% confidence interval (CI) 0.82–0.99], LASr showed a higher diagnostic accuracy in discriminating CA than RELAPS (AUC 0.74, 95% CI 0.59–0.88). LASr and LAScd remained significantly associated with CA in a multivariate regression model. Conclusion : Phasic LAS was significantly reduced in patients with CA and showed a higher diagnostic accuracy in discriminating CA than RELAPS. The additional assessment of phasic LAS may be useful to rule in the possible diagnosis of CA in patients with unclear LVH.

BACKGROUND: Despite previous histopathologic evidence for its presence, the role of myocardial inflammation in the development and progression of cardiac transthyretin amyloidosis (ATTR-CA) remains insufficiently understood. Thus, this study sought to characterize the prevalence and potential prognostic implications of myocardial inflammation in ATTR-CA. METHODS: A retrospective observational study including patients with ATTR-CA diagnosed by endomyocardial biopsy was conducted. Myocardial inflammation was diagnosed through a review of routine endomyocardial biopsy reports. Baseline characteristics were compared using the Mann-Whitney U test and the Pearson χ ² test. Clinical outcomes were monitored via follow-up visits or telephone calls. Primary outcomes were all-cause death and a composite end point of all-cause death or heart failure hospitalization. Kaplan-Meier analyses, as well as univariable and age- and sex-adjusted multivariable Cox regression analyses, were used to assess differences in overall and composite end point-free survival between patients with ATTR-CA with and without myocardial inflammation. RESULTS: A total of 103 patients with ATTR-CA (100 wild type; 3 variant) were enrolled. Median follow-up was 18.2 (8.0–31.1) months. Myocardial inflammation was prevalent in 32% (n=33/103) of patients with ATTR-CA. Among evaluable patients with myocardial inflammation, 96% (n=26/27) and 31% (n=9/29) had elevated CD68 (clusters of differentiation 68)–positive macrophage and CD3 (clusters of differentiation 3)–positive T-cell counts, respectively. Overall survival ( P =0.017) and composite end point-free survival ( P =0.014) were significantly impaired in patients with ATTR-CA with myocardial inflammation (n=33) compared with those without (n=70). Statistical significance for both associations was sustained after adjustment for age and sex, yielding adjusted hazard ratios of 4.72 (95% CI, 1.33–16.71; P =0.016) and 2.30 (95% CI, 1.04–5.11; P =0.041) for all-cause death and the composite end point, respectively. CONCLUSIONS: Our findings affirm previous evidence that myocardial inflammation is present in approximately one-third of all patients with ATTR-CA. Moreover, we provide first data indicating that myocardial inflammation may be associated with a higher risk of death and heart failure hospitalizations in ATTR-CA.

Echocardiographic differentiation of cardiac amyloidosis (CA) and Fabry disease (FD) is often challenging using standard echocardiographic parameters. We retrospectively analyzed the diagnostic accuracy of right heart and left atrial strain parameters to discriminate CA from FD using receiver operating characteristic curve analyses and logistic regression models. A total of 47 FD and 88 CA patients with left ventricular wall thickening were analyzed. The comparison of both cardiomyopathies revealed significantly reduced global and free wall longitudinal right ventricular strain (RVS; global RVS: CA − 13 ± 4%, n = 67, vs. FD − 18 ± 4%, n = 39, p < 0.001) as well as right atrial strain (RAS; reservoir RAS: CA 12 ± 8%, n = 70, vs. FD 26 ± 9%, n = 40, p < 0.001) and left atrial strain (LAS) in CA patients. Individually, global RVS as well as phasic LAS and RAS showed the highest diagnostic accuracy to distinguish CA and FD. The best diagnostic accuracy was achieved by combining the age, basal RV diameter, global RVS, and reservoir and conduit RAS (area under the curve 0.96 [95% CI 0.90–1.00]). Differential echocardiographic diagnostic work-up of patients with suspected CA or FD can be improved by integrating structural and functional parameters of the right heart and the left atrium.Trial registration: DRKS00027403.