Elektra Papadopoulou

Clinical and prognostic significance of serum levels of von Willebrand factor and ADAMTS-13 antigens in AL amyloidosis.

Cardiac dysfunction determines prognosis in amyloid light-chain (AL) amyloidosis. The heart is the central organ of the vascular system in which endothelium function is critical for the circulatory homeostasis, but there are limited data on endothelial function in AL amyloidosis. von Willebrand factor (VWF) has been considered as a marker of endothelial activation and dysfunction, whereas a disintegrin and metalloproteinase with thrombospondin type-1 repeats 13 (ADAMTS-13) cleaves VWF multimers, but both have been associated with prognosis in cardiovascular disease. We measured the serum levels of VWF (VWF:Ag) and ADAMTS-13 antigens in 111 newly diagnosed patients with AL amyloidosis. The levels of VWF:Ag were significantly higher than in healthy controls; 76% of patients with AL had VWF:Ag levels higher than the upper levels of controls. There was no significant association of VWF:Ag levels with patterns of organ involvement, free light-chain levels, the levels of cardiac biomarkers, or renal dysfunction but correlated with low systolic blood pressure. VWF:Ag levels ≥230.0 U/dL were associated with higher probability of early death and poor survival independently of cardiac biomarkers and low systolic blood pressure (SBP). Moreover, among patients with Mayo stage III or stage IIIB (that is stage III with N-terminal pro-brain natriuretic peptide [NTproBNP] >8500 pg/mL) disease, VWF:Ag identified subgroups of patients with very poor outcome. Low ADAMTS-13 levels correlated with high levels of NTproBNP but had no independent prognostic significance. In conclusion, high VWF:Ag levels, probably representing endothelial dysfunction, are associated with prognosis in patients with AL amyloidosis, independently of other features of the disease or cardiac biomarkers.

Cardiac and renal complications of carfilzomib in patients with multiple myeloma

Clinical trials with carfilzomib have indicated a low but reproducible incidence of cardiovascular and renal toxicities. Among 60 consecutive myeloma patients treated with carfilzomib-based regimens who were thoroughly evaluated for cardiovascular risk factors, 12% (95% confidence interval, 3.8%-20%) experienced a reversible reduction of left ventricular ejection fraction (LVEF) by ≥20%, an objective measure of cardiac dysfunction. The incidence of LVEF reduction was 5% at 3 months, 8% at 6 months, 10% at 12 months, and 12% at 15 months, whereas the respective carfilzomib discontinuation rate unrelated to toxicity was 17%, 35%, 41%, and 49%. The presence of any previously known cardiovascular disease was associated with an increased incidence of cardiac events (23.5% vs 7%; P = .07), but there was no association with the dose of carfilzomib or the duration of infusion. Re-treatment with carfilzomib at lower doses was possible. Carfilzomib was commonly associated with a transient reduction of estimated glomerular filtration rate (eGFR) but also improved renal function in 55% of patients with baseline eGFR <60 mL/min/1.73 m2. Further investigation is needed to elucidate the underlying mechanisms of carfilzomib-related cardiorenal toxicity.

Factors Influencing the Twisting and Untwisting Properties of the Left Ventricle during Normal Pregnancy

During pregnancy, important hemodynamic changes occur, consistent with an increase in preload and decrease in afterload and systemic vascular resistance. The aim of the present study was to investigate the changes in left ventricular (LV) strain and rotational properties during the 3 trimesters of normal pregnancy and to examine the factors that drive these changes.

Growth Differentiation Factor 15 Is a New Biomarker for Survival and Renal Outcomes in Light Chain (AL) Amyloidosis

Growth differentiation factor-15 (GDF-15) improves prognostication in patients with cardiovascular disorders in addition to conventional cardiac markers (N-terminal pro B-type natriuretic peptide [NT-proBNP], troponins [Tns]) and has shown prognostic value in patients with renal diseases. In patients with light chain (AL) amyloidosis, cardiac involvement is the major determinant of prognosis, and cardiac markers define prognosis, whereas biomarkers of renal involvement stratify renal risk. We explored the prognostic importance of serum level of GDF-15 in patients with AL amyloidosis in 2 independent cohorts. The prognostic value of GDF-15 level was initially evaluated in a cohort of 107 consecutive previously untreated patients with AL amyloidosis from Athens, Greece, and was then validated in a second cohort of 202 consecutive previously untreated patients from Pavia, Italy. High GDF-15 level was associated with a higher risk of early death and poor overall survival independently of NT-proBNP and high-sensitivity TnT (hsTnT) or hsTnI levels. At the 6-month landmark, reduction of GDF-15 level ≥25% was associated with improved outcome. GDF-15 level ≥4000 pg/mL was associated with a high risk of progression to dialysis, independently of renal risk defined by estimated glomerular filtration rate and proteinuria, in both cohorts; failure to reduce GDF-15 below this level was associated with increased risk at either the 3- or 6-month landmark, independently of the established renal response or progression criteria. In conclusion, GDF-15 has prognostic implications for different outcomes in patients with AL and adds prognostic information independent of that provided by cardiac and renal risk biomarkers.

Myocardial performance index suggests optimal fluid loss during hemodialysis.

Patients on long‐term maintenance hemodialysis (HD) are at high risk of developing cardiovascular disease and suffering various cardiovascular complications during HD.

Atrioventricular Left Ventricular Apical Pacing Improves Haemodynamic, Rotational, and Deformation Variables in Comparison to Pacing at the Lateral Wall in Intact Myocardium: Experimental Study

Aim. To assess the effect on left ventricular (LV) function of atrioventricular (AV) and ventricular pacing at the LV apical or lateral wall and to compare the normal torsional and deformation pattern of the intact LV myocardium with those created by the aforementioned LV pacing modes and sites. Methods. Experiments were conducted in pigs (n = 21) with normal LV function to investigate the acute hemodynamic effects of epicardial AV and ventricular LV pacing at the LV apical or lateral wall. Torsional and deformation indices of LV function were assessed using speckle tracking echocardiography. Results. AV pacing at the apex revealed a significant reduction in the radial strain of the base (P < 0.03), without affecting significantly the ejection fraction and the LV torsion or twist. In contrast, AV pacing at the lateral wall produced, in addition to the reduction of the radial strain of the base (P < 0.01), significant reduction of the circumferential and the radial strain of the apex (both P < 0.01) as well as of the ejection fraction (P < 0.002) and twist (P < 0.05). Conclusions. In pig hearts with intact myocardium, LV function is maintained at sinus rhythm level when AV pacing is performed at the LV apex.

Acute Haemodynamic and Echocardiographic Effects of Multiple Configurations of Left Ventricular Pacing Sites in Acute Myocardial Infarction: Experimental Study

BACKGROUND Left ventricular (LV) pacing is unsuccessful in a significant number of patients, mainly due to sub-optimal LV pacing location. Nevertheless, data about the impact of different pacing sites on LV function in ischaemic myocardium are scarce. The purpose of this study was to investigate the effect of combinations of alternative LV pacing sites on LV mechanics after experimental acute anterior myocardial infarction (AMI), in order to define the optimal configuration. METHODS Atrioventricular epicardial pacing at alternative pacing sites was performed in 16 healthy pigs simultaneously, after experimental AMI. Standard right ventricular (RV) apical pacing was combined with: i) LV apex lateral wall; ii) LV basal posterior wall; iii) LV basal anterior wall, and; iv) LV basal anterior wall + LV basal posterior wall. Moreover the pacing configurations of, v) LV basal posterior wall + LV apex lateral wall; vi) LV basal posterior wall + LV basal anterior wall, and; vii) LV basal anterior wall + LV apex lateral wall were also investigated. Haemodynamic parameters, together with classic and novel echocardiographic indices were used, to evaluate the effect of each pacing combination. A speckle tracking technique using EchoPAC software was used. RESULTS After AMI, the pacing combination of LV apex lateral wall and LV basal posterior wall had the most favourable effect on LV function, leading to similar haemodynamic and torsional effects with sinus rhythm (all variables p>0.05). CONCLUSIONS In pig hearts after AMI, the combination of pacing LV apex lateral wall and LV basal posterior wall managed to maintain the LV function at a level comparable to the sinus rhythm.