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.

Assessment of the correlation between two defining criteria for bidirectional isthmic block in the ablation of typical atrial flutter.

BACKGROUND: A complete, bidirectional conduction block in the cavotricuspid isthmus (CTI) represents the end-point of the typical atrial flutter ablation. We investigated the correlation between two criteria for successful ablation, one based on the atrial bipolar electrogram morphology before and after complete CTI conduction block, compared to the standard criteria of differential pacing and reversal in the right atrial depolarization sequence during coronary sinus (CS) pacing. METHOD: We conducted a retrospective study in 111 patients (81 males, average age 62±10 years) who underwent an atrial flutter ablation during September 2007 - July 2009 in the Cardiology - Rehabilitation Hospital, UMF Cluj-Napoca. We assessed the presence of a bidirectional block at the end of the procedure using the standard criteria. We then analyzed the morphology of the bipolar atrial electrograms adjacent to the ablation line, before and after CTI conduction block. RESULTS: A change from a qRs morphology to a rSr' morphology when pacing from the coronary sinus and from a rsr' morphology to a QRS morphology when pacing from the low-lateral right atrium was associated with a CTI conduction block. Sensitivity (Se), specificity(Sp), positive predictive value (PPV), negative predictive value (NPV) were 96%, 89%, 99% and 67% respectively. CONCLUSION: Our study suggests that the analysis of the atrial bipolar electrogram next to the ablation line before and after CTI ablation may be used as a reliable criterion to validate CTI conduction block due to its high sensitivity, specificity and positive predictive value.

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.

Exercise testing for assessing the effectiveness of digitalis therapy in compensated heart diseases.

Exercise pulse rate (EPR) during a 6-minute exercise testing and recovery pulse rate (RPR) 5 minutes following the test were determined in three groups of subjects before and after rapid digitalization. Ten normal subjects showed no significant changes in heart rate after rapid digitalization. EPR and RPR decreased and FPR/RPR ratio increased significantly after administration of the cardiac glycoside in 7 patients with congestive heart failure. A similar response was found in 25 out of 36 patients with compensated heart disease (69.4%). Such a response suggests a beneficial effect of chronic digitalis therapy in cardiac patients without heart failure.

The effect of intravenous potassium canrenoate in patients with severe heart failure and digitalis toxicity.

In 16 patients with critical condition due to severe heart failure associated with digitalis toxicity, the effects of potassium canrenoate (AldactoneR) administered intravenously were studied. Rhythm and conduction disturbances disappeared or improved in all instances. This effect was well correlated with an increase of serum potassium concentration. In 13 patients, after 1-2 days of Aldactone therapy, heart failure improved, which could be explained by a diuretic effect and by a possible inotropic action of aldactone. It is concluded that intravenous Aldactone is useful in patients with severe heart failure and digitalis toxicity in whom diuretics are often ineffective and even dangerous.