Utility of Doppler myocardial imaging, cardiac biomarkers, and clonal immunoglobulin genes to assess left ventricular performance and stratify risk following peripheral blood stem cell transplantation in patients with systemic light chain amyloidosis (Al).

BACKGROUND: Cardiac dysfunction is a well-recognized complication of light chain amyloidosis (AL). Autologous stem cell transplant (auto-SCT) has emerged as a successful treatment modality for AL patients. In this study, we examined the effect of clonal immunoglobulin light chain genes (VL), which encodes the immunoglobulin light chain protein that ultimately forms amyloid, on cardiac function, in the context of auto-SCT and its impact on overall survival. METHODS: Longitudinal Doppler myocardial imaging parameters along with cardiac biomarkers were used to assess for cardiac function pre and post auto-SCT. RESULTS: VL gene analysis revealed that Vl genes, in particular VlVI, were associated with worse cardiac function parameters than Vk genes. Clonal VL genes appeared to have an impact on left ventricular (LV) function post-transplant and also influenced mortality, with specific VL gene families associated with lower survival. Another key predictor of mortality in this report was change in tricuspid regurgitant flow velocity following auto-SCT. Correlations were also observed between systolic strain rate, systolic strain and VL genes associated with amyloid formation. CONCLUSIONS: Clonal VL gene usage influences global cardiac function in AL, with patients having VlVI and VlII-III-associated amyloid more severely affected than those having Vk or VlI amyloid. Pulsed wave tissue Doppler imaging along with immunoglobulin gene analysis offers novel insights into prediction of mortality and cardiac dysfunction in AL after auto-SCT.

Integrating research into clinical practice: development of an echocardiography research unit.

Introducing a research program into an echocardiography clinical practice can pose many challenges. Some initial factors to consider are the possible effects on the current clinical schedule and the equipment and personnel resources required to support the research projects. More importantly, how can an organization successfully complete reliable and accurate research projects? Here, we describe our experience with establishing an echocardiography research center within our clinical echocardiography practice. In addition, we identify key staff roles, highlight our current research practice methods, and suggest essential components that may prove advantageous when incorporating echocardiography research into a clinical practice.

Effects of quinapril on left atrial structural remodeling and arterial stiffness.

Left atrial (LA) enlargement, left ventricular (LV) diastolic dysfunction, and increased arterial stiffness are all associated with adverse cardiovascular outcomes. The rate, magnitude, and concordance of modifiability of these risk markers have not been well characterized. Twenty-one patients (mean age 69 +/- 8 years; 52% women) with isolated diastolic dysfunction and indexed LA volumes > or =32 ml/m(2) were randomly assigned to receive either quinapril at a target dose of 60 mg/day or matching placebo for 12 months. Echocardiographic maximum LA volume and LV diastolic function and arterial stiffness by the augmentation index were measured at baseline and 6 and 12 months. Analysis was based on intention to treat. Baseline characteristics were comparable between the treatment (n = 9) and placebo (n = 12) groups. The mean reduction in LA volume of 4.2 +/- 7.8 ml/m(2) in the quinapril group was significant (p = 0.01) compared with the increase in LA volume in the placebo group (5.5 +/- 8.1 ml/m(2)). This represents a relative improvement of 9.7 ml/m(2). Change in LV filling pressure in terms of E/e' and diastolic function grade did not reach significance. A reduction in the augmentation index was associated with a decrease in indexed LA volume (odds ratio 11, p = 0.046), independent of changes in systolic blood pressure. In conclusion, LA structural remodeling appeared reversible with quinapril, which occurred in parallel with an improvement in arterial stiffness but independent of blood pressure changes.

Relation of tissue displacement and strain to invasively determined right ventricular stroke volume.

The role of echocardiography in the clinical assessment of right ventricular (RV) systolic function remains limited. Limited data exist on the potential use of newer techniques for RV function assessment. Conventional echocardiography and tissue Doppler echocardiography (TDE) were performed during right-sided cardiac catheterization in 46 patients. Thermodilution or the Fick-derived RV stroke volume indexed (RVSVI) indexed to body surface area was used as the reference standard. Univariate and multivariate regression analyses were used to test correlations between RVSVI and various echocardiographic and TDE-derived parameters. In a subset of 12 subjects, changes in echocardiographic and TDE variables to reduced afterload from intravenous epoprostenol were measured. TDE-derived RV tissue displacement and systolic strain best predicted the RVSVI (r = 0.63, p = 0.001; r = 0.48, p = 0.002, respectively). The prediction improved after adjustment for tricuspid regurgitation jet vena contracta width (r = 0.74, p < 0.0001; r = 0.60, p < 0.001, respectively). Assuming a RVSVI of > or =30 ml/m(2) as normal, a RV displacement cutoff of 15 mm yielded a sensitivity of 100% and a specificity of 41% for RV dysfunction, and an RV systolic strain cutoff of 20% yielded a sensitivity of 91% and a specificity of 63%. The percentage change of RV systolic displacement correlated well with the percentage change of RVSVI after epoprostenol infusion (r = 0.75, p < 0.001). In conclusion, TDE-derived RV displacement and strain closely correlate with RVSVI and appropriately track load-related changes in RV function. These new parameters may help provide the noninvasive, quantitative assessment of RV function.