Arterial-myocardial coupling in primary AL amyloidosis. A validation study of vascular involvement

Abstract Background Primary AL amyloidosis is a rare yet lethal systemic disorder. Previously published own and others’ work indicated that vascular involvement in AL cardiac amyloidosis defined as low blood pressure or paradoxical vasodilation may independently affect survival. Mechanistic data will pave the way to validate the clinical role of vascular involvement in these patients. Purpose We sought to explore the presence of arterial-myocardial coupling in AL amyloidosis by investigating associations between markers of vascular and cardiac involvement. Methods We consecutively recruited n=152 newly diagnosed patients with AL amyloidosis that underwent thorough vascular examination including reactive vasodilation (flow mediated vasodilation, FMD and vasodilation in response to cold-pressor test) using high resolution ultrasonography. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (PWV) and aortic pressures and markers of arterial wave reflections were estimated using radial artery tonometry. In a subgroup of patients, transthoracic echocardiography (n=152) and cardiac magnetic resonance (CMR) (n=59) were performed. Results Vascular reactivity correlated with global longitudinal strain (GLS), left ventricle ejection fraction (LVEF)/GLS ratio and worse LV volumes. Vasodilation post-cold pressure test was correlated with LV mass. cSBP exhibited a negative correlation with markers of heart involvement, wall thickness markers, GLS, and CMR tissue characterization markers. A positive correlation between cSBP and LVEF, rotation and twist strain, myocardial work and contractility markers and late gadolinium enhancement (LGE). cDBP was associated with systolic function and contractility markers, with myocardial work indices and LGE. A negative relationship with GLS, LA strain, RV GLS and LA diameter and E/e’ was noted. In addition, T2 was negatively correlated with cDBP. SBP was correlated positively with LVEF, contractility markers, and LGE myocardium and negatively correlated with biomarkers of heart involvement, GLS, CMR structure and tissue characterization. DBP was positively correlated with LGE and myocardial work. A negative relation with NTproBNP, E/e’, RVSP, LA diameter and T2 mapping was noted. Time of wave reflections (Tr) was negatively correlated with rotation strain and positively correlated with circumferential strain, LA strain and LV structure. Ai@75 was positively correlated with myocardial work and contractility markers, and LGE. Ai@75 was negatively correlated with markers of heart involvement, LV structure, E/e’, worse GLS and adverse CMR tissue characterization. Conclusion Markers of peripheral vascular dysfunction were associated with cardiac structure and function acquired both with echocardiography and CMR in AL amyloidosis. This arterial-myocardial coupling supports the clinical role of peripheral vascular involvement in this disease and warrants further investigation.