Evaluation of echocardiographic features and cardiac biomarkers in patients with AA amyloidosis: a retrospective comparative study with patients with al amyloidosis and hypertrophic cardiomyopathy

Cardiac amyloidosis (CA) is a well-known feature of AL amyloidosis (AL-A) and transthyretin amyloidosis, and its detection is important due to its association with a poor prognosis. In this study, we aimed to evaluate cardiac dysfunction with echocardiographic features alongside cardiac biomarkers in patients with AA-A in a controlled design with appropriate control groups. This retrospective observational study was conducted at a referral center for amyloidosis in Istanbul, Türkiye. The study population consisted of patients with AA-A, as well as patients with AL-A and hypertrophic cardiomyopathy (HCM) as diseased controls. We included 139 patients (56% male) with AA-A, 89 patients (52% male) with AL-A, and 54 (57.4% male) patients with HCM in the study. The mean interventricular septum diameter (IVSd) was 11.8 ± 2.3, 14.6 ± 3.7, and 17.4 ± 4.3 mm in AA-A, AL-A, and HCM, respectively (p < 0.001 for each). The mean posterior wall diameter (PWd) was 10.5 ± 1.7, 12.9 ± 2.8, and 12 ± 1.6 mm in AA-A, AL-A, and HCM, respectively (p < 0.001 for AA-A and AL-A and AA-A and HCM; p = 0.056 for AL-A and HCM). The fulfillment of the Gertz et al. criteria was 34.5% in AA-A, 68.5% in AL-A, and 0% in HCM (p < 0.001 for each). Additionally, 4.3% in AA-A, 27.3% in AL-A, and 2% in the HCM group fulfilled the PWd > 12.5 mm plus troponin > 13.15 pg/mL plus serum creatinine (Screa)>1.085 mg/dL criterion. In multivariate analysis, PWd and left ventricular diastolic dysfunction were associated with suspected CA according to the Gertz et al. criteria in patients with AA-A. In Cox regression analysis, higher PWd and reduced EF were associated with increased mortality in patients with AA-A. Survival analysis revealed lower survival in patients who met the Gertz et al. criteria, the Gertz et al. plus granular echogenicity, the PWd > 12.5 mm plus troponin > 13.15 pg/mL plus Screa>1.085 mg/dL criteria, and patients who had increased PWd, reduced ejection fraction, advanced diastolic dysfunction, and granular echogenicity. In ROC analysis, troponin > 24.5 pg/mL had 100% sensitivity and 66.1% specificity, and pro-BNP > 636.5 pg/mL had 94.4% sensitivity and 53.7% specificity, yielding higher mortality in patients with AA-A. A considerable proportion of AA-A patients may be at risk of developing cardiac dysfunction that may be suggestive of CA. Increased posterior wall thickness, granular echogenicity, and advanced diastolic dysfunction may be suggestive echocardiographic features of suspected CA in patients with AA-A. These findings of myocardial dysfunction warrant further investigation to evaluate cardiac involvement in AA-A patients. Prospective studies with histopathological and/or MRI confirmation are needed to better define the causes of cardiac dysfunction in AA-A.