Functional correlates of N-terminal natriuretic peptide type B (NT-proBNP) response to therapy in cardiac light chain (AL) amyloidosis

In cardiac (light chain) AL amyloidosis, a decrease in circulating free light chains (FLCs) higher than 50% is associated with reduced Nterminal natriuretic peptide type B (NT-proBNP) serum concentration, improvement of heart failure symptoms, and prolonged survival. To assess the functional correlates of these changes, echocardiographic indices of systolic and diastolic regional function were compared at diagnosis and after response achievement in 32 patients. FLCs and NT-proBNP were concomitantly measured. No significant change in left ventricular wall thicknesses, chamber dimensions, indices of diastolic dysfunction or ejection fraction was observed after chemotherapy. In contrast, systolic longitudinal excursion of both the interventricular septum and the lateral wall was increased (from 5.2+ 1.4 to 6.8+ 1.5 and from 6.2+ 1.3 to 7.7+ 1.4 mm, respectively; p5 0.05 for both). These changes were significantly correlated with the extent of FLCs (p1⁄4 0.05) and NTproBNP (p1⁄4 0.05) reduction. In cardiac AL amyloidosis, hematological response to chemotherapy and reduction of cardiac biomarkers are associated with improved indices of regional systolic function. Introduction: In patients with AL amyloidosis and cardiac involvement, a decrease in circulating free light chains (FLCs) higher than 50% is associated with a reduction in N-terminal natriuretic peptide type B (NT-proBNP) serum concentration, improvement of symptoms of heart failure, and prolonged survival [1], despite the amount of cardiac amyloid deposits remains unaltered, as measured by echocardiography. Notably, it has been recently suggested that NT-proBNP changes may not ‘track’ FLCs reduction when immune modulator drugs are included in the chemotherapy schedule [2]. However, since NT-proBNP has been shown as a robust prognostic marker in the setting of cardiac AL [3,4], it is important to assess what are the functional correlates of the reduction of the circulating amyloidogenic precursor caused by chemotherapy, in parallel with both FLCs and NT-proBNP changes. Aim of the present study was therefore to assess changes in cardiac function associated with reduction in circulating FLCs and serum NT-proBNP concentration in patients with cardiac AL amyloidosis achieving hematologic response. Methods: In 32 patients with cardiac AL amyloidosis who achieved hematologic response (defined as a reduction of circulating FLCs by more than 50% [1]) after three cycles of chemotherapy, echocardiographic indices of systolic, and diastolic regional function, as well as serum NT-proBNP were compared at diagnosis and after response achievement. Echocardiography was performed by a single operator via an Acuson Sequoia 512 machine (Siemens Healthcare, Milano, Italy). Left ventricular (LV) wall thicknesses and chamber dimensions were measured by 2D-guided M-mode evaluation in the longitudinal parasternal view, according to the standards of the American Society of Echocardiography [5]. Diastolic function was characterized in terms of: transmitral Doppler early (E) and atrial (A) velocities, E deceleration time, pulmonary venous flow velocity, early tissue Doppler (TDI) peak velocity (E’) and E/E’ ratio. Systolic function was evaluated as: LV ejection fraction (EF), longitudinal excursion of the mitral annulus at the septum, and at lateral wall. Patients with significant valve disease, previous myocardial infarction, atrial fibrillation, or chronic obstructive lung disease were excluded from the analysis. Results and discussion: Chemotherapy-related reduction in circulating FLCs was paralleled by a 47% median decrease in serum NT-proBNP, thereby confirming previous observations [1]. No significant change in LV wall thicknesses, end-diastolic and end-systolic chamber dimensions, global systolic function, or indices of diastolic function was observed after chemotherapy. In detail, when comparing data at diagnosis and after treatment, interventricular septum thickness was 14.2+ 2.1 and 14.3+ 2.3 mm, posterior wall thickness was 13.9+ 2.1 and 13.9+ 2.3 mm, LV diameters were 42+ 3 and 44+ 4 mm at end-diastole and 30+ 2 and 29+ 4 at end-systole, and EF was 55+ 4% and 54+ 4%, respectively (p1⁄4ns for all comparisons). No significant change in transmitral Doppler peak velocities, E deceleration time, pulmonary venous flow velocity, early TDI peak velocity (E’), and E/E’ ratio was observed. In contrast, longitudinal excursion of both the interventricular septum and the 96