Myocardial Inflammation in Cardiac Transthyretin Amyloidosis: Prevalence and Potential Prognostic Implications

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.