Global Left Ventricular Myocardial Work Efficiency in Heart Failure Patients with Cardiac Amyloidosis: Pathophysiological Implications and Role in Differential Diagnosis

INTRODUCTION: Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy and a common cause of heart failure with preserved and mid-range ejection fraction (HFpEF and HFmrEF). Left ventricular (LV) systolic assessment is pivotal in differential diagnostic and prognostic stratification in CA. However, nondeformation and deformation-based parameters classically implied had many limitations. Myocardial work (MW) has been recently introduced for the evaluation of myocardial performance, in a load-independent fashion, in patients with cardiomyopathies. AIMS: This study aimed to evaluate MW parameters in LV performance assessment in CA and their possible role in differential diagnosis between AL and ATTR forms, compared with other echocardiographic parameters, also exploring the possible association between MW parameters and blood biomarkers. MATERIALS AND METHODS: The study population consisted of 25 patients with CA (10 with AL amyloidosis and 15 with wild-type ATTR [ATTRwt] form) and HFpEF or HFmrHF, enrolled between March 2018 and December 2019, undergoing a comprehensive clinical, biochemical, and imaging evaluation. Ten healthy individuals were studied as controls. ATTR patients had a noninvasive diagnosis of wtATTR-CA (positive (99m)Tc-hydroxy methylene-diphosphonate scintigraphy with a negative hematological screening), while AL patients underwent endomyocardial biopsy. All patients underwent standard transthoracic echocardiography. MW and related indices were estimated using a vendor-specific module. RESULTS: Compared to the ATTRwt group, patients in the AL group showed a more pronounced myocardial performance impairment assessed by Global Word Efficiency (GWE: 83.5% ± 6.3% vs. 88.2% ± 3.6%; P = 0.026). In multiple linear regression analysis, cardiac troponin I (Β = −0.55; P < 0.0001), global longitudinal strain (Β =0.35; P < 0.008), and regional relative strain ratio (Β = −0.30; P < 0.016) were significant predictors of GWE reduction in CA patients. At receiver operating characteristics curve analysis, among all other deformation-based and nondeformation-based echocardiographic parameters, GWE showed the highest area under the curve (AUC) (AUC 0.74; 95% CI: 0.55–0.96; P < 0.04). The optimal cutoff was determined by sensitivity/specificity analysis: a GWE < 86.5% identified patients with AL amyloidosis with a sensitivity and specificity, respectively, of 80.0% and 66.7%. CONCLUSIONS: The results of our pivotal study seem to highlight the importance of new deformation parameters to study myocardial performance in patients with CA, and to differentiate between AL CA and ATTR CA.