Galectin-3 as a marker for clinical prognosis and cardiac remodeling in acute heart failure.

BACKGROUND: Galectin-3 has been reported as a mediator of heart failure (HF) development and progression. Most studies, however, have been conducted on patients with chronic HF rather than acute HF (AHF). The aim of this study was to confirm galectin-3 as a prognostic marker in subjects with AHF and to investigate its possible relationship with left ventricular (LV) remodeling. METHODS: A total of 69 patients hospitalized with a primary diagnosis of AHF were followed up for 18 months. Galectin-3 and echocardiographic parameters were measured at baseline and after 6 months. Survival analysis and exploratory analysis of LV remodeling were performed. RESULTS: Patients with high baseline galectin-3 values (>16.5 ng/ml) had a significantly worse survival profile over the 18-month follow-up (log-rank test, p = 0.017), with Cox proportional hazards modeling showing a crude hazard ratio (HR) of 4.66 (95% CI = 1.16-18.67; likelihood-ratio test, p = 0.037) for all-cause mortality. Changes in galectin-3 levels (1 SD increase over 6 months) proved to be a significant explanatory factor for HF hospital re-admission in the short term when compared with quasi-stationary galectin-3 levels: worse Kaplan-Meier survival curves (log-rank test, p = 0.001) and a crude HR of 4.44 (95% CI = 1.76-11.18; likelihood-ratio test, p = 0.004). A significant association was found between the pathological evolution of relative wall thickness, LV end-diastolic diameter, LV end-diastolic volume, and increasing levels of galectin-3 in the short term (Cochran-Mantel-Haenszel test, p < 0.01). CONCLUSION: Galectin-3 can predict long-term mortality in patients with AHF. The results of our study suggest a possible relation between left ventricular remodeling and increasing galectin-3 levels.

Customized laboratory TLR4 and TLR2 detection method from peripheral human blood for early detection of doxorubicin-induced cardiotoxicity.

Cancer treatments can have significant cardiovascular adverse effects that can cause cardiomyopathy and heart failure with reduced survival benefit and considerable decrease in the use of antineoplastic therapy. The purpose of this study is to assess the role of TLR2 and TLR4 gene expression as an early marker for the risk of doxorubicin-induced cardiomyopathy in correlation with early diastolic dysfunction in patients treated with doxorubicin. Our study included 25 consecutive patients who received treatment with doxorubicin for hematological malignancies (leukemia, lymphomas or multiple myeloma), aged 18-65 years, with a survival probability>6 months and with left ventricular ejection fraction>50%. Exclusion criteria consisted of the following: previous anthracycline therapy, previous radiotherapy, history of heart failure or chronic renal failure, atrial fibrillation, and pregnancy. In all patients, in fasting state, a blood sample was drawn for the assessment of TLR2 and TLR4 gene expression. Gene expression was assessed by quantitative reverse transcription PCR (qRT-PCR) using blood collection, RNA isolation, cDNA reverse transcription, qRT-PCR and quantification of the relative expression. At enrollment, all patients were evaluated clinically; an ECG and an echocardiography were performed. The average amount of gene expression units was 0.113 for TLR4 (range 0.059-0.753) and 0.218 for TLR2 (range 0.046-0.269). The mean mRNA extracted quantity was 113 571 ng/µl. As for the diastolic function parameters, criteria for diastolic dysfunction were present after 6 months in 16 patients (64%). In these patients, the mean values for TLR4 were 0.1198625 and for TLR2 were 0.16454 gene expression units. As for the diastolic function parameters, criteria for diastolic dysfunction were present after 6 months in 16 patients (64%). In these patients, the mean value for TLR2 was 0.30±0.19 and for TLR4 was 0.15±0.04. The corresponding values for the patients who did not develop diastolic dysfunction were 0.16±0.07 for TLR2 (P=0.01) and 0.11±0.10 for TLR4 (P=0.2). Our study suggests that TLR4 and TLR2 expression is higher in patients under doxorubicin therapy who develop diastolic dysfunction. This may suggest a predisposition to myocardial involvement, a higher sensitivity to doxorubicin cardiac effects.

The effectiveness and tolerance of betablockers in elderly patients (> or = 70 years) with heart failure.

UNLABELLED: The beta blockers (BB) being less prescribed in elderly patients (P) with heart failure (HF), the aim of this study was to assess the effectiveness and tolerance of BB (meteoprolol, bisoprolol or carvedilol) given on the top of the conventional therapy in HF due to LV systolic dysfunction in P > or = 70 year (n=57, group 1) and < 70 year (n=101, group 2). Differences in baseline clinical characteristics between the 2 groups were not significant. The BB doses given in group 1 P was lower but the difference was significant for bisoprolol only. Intolerance to BB imposing withdrawal occurred in 12% of group 1 P and in 10% group 2 P (p>0.05). Symptomatic improvement expressed as a significant decreases in NYHA class was observed in both groups. Readmission for worsening HF was needed in 42% vs. 39% while 1 year mortality rate was 11.4% vs. 10.4% in group 1 and 2 P respectively (p>0.05). CONCLUSION: BB are tolerated and seem to be effective in most elderly P with HF. Therefore, BB should be tried in all HF P without contraindication irrespective of age.