Early Detection of Cardiac Systolic Functional Impairment and Correlation with NT-ProBNP Change in AL Amyloidosis by Cardiac Lateral Wall Tissue Doppler S Wave.

Abstract 2814

Poster Board II-790

N-terminal fragment of brain natriuretic peptide is a cardiac biomarker that has prognostic significance in amyloidosis and NT-ProBNP can rapidly change after completion of chemotherapy. We and others who have previously reported such changes in NT-ProBNP to be of prognostic significance but there was no cardiac “progression” or “improvement” according to the international amyloidosis consensus criteria (Gertz et al 2005) in the majority - making this finding difficult to explain. We now report subtle changes in left ventricular systolic function using lateral wall tissue Doppler as a new robust and reproducible parameter correlating well with such changes in NT-ProBNP.

Patients with cardiac amyloidosis as defined by the international consensus criteria who had good renal function (creatinine clearance >30ml/min), received chemotherapy and had a significant change in NT-ProBNP after chemotherapy were identified from the database of the UK National Amyloidosis Centre. A significant change in NT-ProBNP was defined as minimum rise or fall of 30% over the baseline pre-treatment value.

Ninty seven patients with identified. All analysis was repeated on stored off line data on EchoPAC” in accordance with British Society of Echocardiography guidelines with special focus on ejection fraction (EF) (Biplane Simpson's method), longitudinal 2D strain, lateral TDI S wave (Tissue Doppler Imaging) and mean left ventricular wall thickness. At baseline the mean EF was 59%, mean LV wall thickness 13mm and mean TDI S wave velocity 0.07m/sec. 76/97 (78%) patients showed a significant increase in the NT-proBNP levels and 21/97 (22%) showed a significant a decrease. There was a significant correlation between the free light chain (FLC) level and NT-ProBNP at diagnosis (correlation coefficient 0.322; p <0.001). NT-ProBNP decreased from median 444 to 144 pMol/L (p=0.021) among patients who had a complete FLC response. There was also good correlation between the NT-ProBNP level with interventricular septal and left ventricular posterior wall thickness (spearman correlation coefficient 0.55, significance 0.01) at baseline. None of the patients had cardiac progression or improvement by echocardiography according to the international consensus criteria . In both groups of patients (increase or decrease in NT-ProBNP), there was no significant change in the LV wall thickness. In patients with a decrease in the NT-proBNP, there was no significant increase in the ejection fraction or longitudinal 2-D strain in the evaluable cases. But there was a significant improvement in the mean lateral TDI S wave (a marker of longitudinal LV systolic function) from 0.07 m/s to 0.08m/s (p=0.02) suggesting improvement in systolic function. In patients with an increase in the NT-ProBNP, there was a significant decrease in the mean EF from 60% to 56% (p=0.032). The longitudinal 2D strain also decreased significantly by mean of 10% (-13.9% to -12.6%; p=0.009) and the lateral TDI S wave also showed significant worsening with a decline from 0.09m/sec to 0.07m/sec (p <0.001).

NT-ProBNP changes after chemotherapy have remained difficult to explain. The international consensus criteria for cardiac progression or improvement by echocardiography - a 2 mm change in the LV wall thickness or 20% change in EF - are relatively insensitive and the clinical criteria (change in NYHA class by 2) are not robust or reproducible to detect cardiac improvement or progression. Lateral TDI S wave is a robust and reproducible parameter that correlates well with both an increase and decrease drop in NT-ProBNP levels. This suggests that there are subtle changes to the left ventricular systolic function which correlate well with change in NT-ProBNP and are of prognostic significance. These changes in systolic function occur well before any substantial diastolic functional change or change in wall thickness. This interesting finding needs further validation in larger groups and if confirmed should be considered for incorporation in the consensus criteria for cardiac progression or improvement.