Recurrence of cerebrovascular events in young adults with a secundum atrial septal defect

Background: The recurrence rate for cerebrovascular ischemic events in patients after a first TIA or CVA with an atrial septal defect type 2 (ASD2) remains unknown. At present, there are no guidelines with respect to appropriate treatment. The aim of this study was to determine incidence rates of recurrent cerebrovascular events in patients with ASD2. Methods: A multicenter, retrospective study was performed at selected centres in The Netherlands, United Kingdom and United States. All patients with ASD2 and a prior cerebrovascular event were identified from available databases. Clinical data were retrieved from medical files, electronic databases and radiographic charts. Results: Fifty-six adult patients born between 1950 and 1990 (median age at first cerebrovascular event 37.5, range 15-53 years) were recruited. Recurrent events (9 TIA, 2 CVA) were recorded in 11 patients (19.6%) during a median follow-up time of 5.3 years (range 0.2-28.9). Nonclosure of the defect was the only significant predictor of a recurrent event (p=0.01). Conclusion: Patients with an ASD2 and a history of a cerebrovascular ischemic event have a substantial risk for recurrent events. Closure of the ASD2 seems to substantially decrease the risk of recurrence. However, prospective randomized trials are needed to confirm our findings. (C) 2009 Elsevier Ireland Ltd. All rights reserve

Galectin-3 is an independent marker for ventricular remodeling and mortality in patients with chronic heart failure

<p>Galectin-3 (Gal-3) is a recently discovered marker for myocardial fibrosis and elevated levels are associated with an impaired outcome after short-term follow-up in heart failure (HF) patients. However, whether Gal-3 is related to cardiac remodeling and outcome after long-term follow-up is unknown. Therefore, we determined the utility of Gal-3 as a novel biomarker for left ventricular remodeling and long-term outcome in patients with severe chronic HF.</p><p>A total of 240 HF patients with New York Heart Association (NYHA) Class III and IV were included. Patients were followed for 8.7 +/- A 1 years, had a mean age of 71 +/- A 0.6 years and 73 % of the study population was male. Circulating levels of NT-proBNP and Gal-3 were measured. Serial echocardiography was performed at baseline and at 3 months. At baseline median left ventricular end-diastolic volume (LVEDV) was 267 mL [interquartile range 232-322]. Patients were divided into three groups according to the change in LVEDV. Patients in whom the LVEDV decreased over time had significant lower levels of Gal-3 at entry compared to patients in whom the LVEDV was stable or increased (14.7 vs. 17.9 vs. 19.0 ng/mL; p = 0.004 for trend), whereas no significant differences were seen in levels of NT-proBNP (p = 0.33). Multivariate linear regression analyses revealed that Gal-3 levels were positively correlated to change in LVEDV (p = 0.007). In addition, Gal-3 was a significant predictor of mortality after long-term follow-up (p = 0.001).</p><p>Gal-3 is associated with left ventricular remodeling determined by serial echocardiography and predicts long-term mortality in patients with severe chronic HF.</p>

Incremental Prognostic Power of Novel Biomarkers (Growth-Differentiation Factor-15, High-Sensitivity C-Reactive Protein, Galectin-3, and High-Sensitivity Troponin-T) in Patients With Advanced Chronic Heart Failure

<p>Elevated natriuretic peptides provide strong prognostic information in patients with heart failure (HF). The role of novel biomarkers in HF needs to be established. Our objective was to evaluate the prognostic power of novel biomarkers, incremental to the N-terminal portion of the natriuretic peptide (NT-proBNP) in chronic HF. Concentrations of circulating NT-proBNP, growth differentiation factor 15 (GDF-15), high-sensitivity C-reactive protein (hs-CRP), galectin-3 (Gal-3), and high-sensitivity troponin T (hs-TnT) were measured and related to all-cause long-term mortality. Of 209 patients (age 71 +/- 10 years, 73% male patients, 97% New York Heart Association class III), 151 (72%) died during a median follow-up of 8.7 +/- 1 year. The calculated area under the curve for NT-proBNP was 0.63, GDF-15 0.78, hs-CRP 0.66, Gal-3 0.68, and hs-TnT 0.68 (all p <0.01). Each marker was predictive for mortality in univariate analysis. In multivariate analysis, elevated concentrations of GDF-15 (hazard ratio [HR] 1.41, confidence interval [CI] 1.1 to 178, p = 0.005), hs-CRP (111R 1.38, CI 1.15 to 1.67, p = 0.001), and hs-TnT (HR 1.27, CI 1.06 to 1.53, p = 0.008) were independently related to mortality. All novel markers had an incremental value to NT-proBNP, using the integrated discrimination improvement. In conclusion, in chronic HF, GDF-15, hs-CRP, and hs-TnT are independent prognostic markers, incremental to NT-proBNP, in predicting long-term mortality. In this study, GDF-15 is the most predictive marker, even stronger than NT-proBNP. (C) 2013 Elsevier Inc. All rights reserved.</p>

Myocardial fibrosis and pro-fibrotic markers in end-stage heart failure patients during continuous-flow left ventricular assist device support

OBJECTIVES: During support with a left ventricular assist device (LVAD), partial reverse remodelling takes place in which fibrosis plays an important role. In this study, we analysed the histological changes and expression of fibrotic markers in patients with advanced heart failure (HF) during continuous-flow LVAD (cf-LVAD) support. METHODS: In 25 patients, myocardial tissue at the time of LVAD implantation (pre-LVAD) was compared with tissue from the explanted left ventricle (post-LVAD). Interstitial fibrosis and cardiomyocyte size were analysed pre-and post-LVAD. Plasma was obtained from all patients before and during LVAD support. Plasma levels, cardiac mRNA and protein expression of brain natriuretic peptide (BNP), galectin-3 (Gal-3), connective tissue growth factor (CTGF), osteopontin (OPN) and transforming growth factor beta-1 were determined. RESULTS: Fibrosis increased during cf-LVAD unloading (P <0.05). Cardiomyocytes elongated (P <0.05), whereas cross-sectional area did not change. BNP, Gal-3, CTGF and OPN were significantly elevated pre-LVAD in comparison with controls. BNP decreased significantly after 1 month of cf-LVAD support (P <0.001) to near-normal levels. Pro-fibrotic markers remained elevated in comparison with controls. CONCLUSIONS: cf-LVAD support is associated with lengthening of cardiomyocytes, without alterations in diameter size. Remarkably, myocardial fibrosis increased as well as circulating pro-fibrotic markers. Whether the morphological changes are a direct effect of reduced pulsatility during cf-LVAD support or due to HF progression requires further investigation

MicroRNA Expression in Myocardial Tissue and Plasma of Patients with End-Stage Heart Failure during LVAD Support : Comparison of Continuous and Pulsatile Devices

Aim Pulsatile flow left ventricular assist devices (pf-LVADs) are being replaced by continuous flow LVADs (cf-LVADs) in patients with end-stage heart failure (HF). MicroRNAs (miRs) play an important role in the onset and progression of HF. Our aim was to analyze cardiac miR expression patterns associated with each type of device, to analyze differences in the regulation of the induced cardiac changes. Methods and Results Twenty-six miRs were selected (based on micro-array data and literature studies) and validated in myocardial tissue before and after pf- (n = 17) and cf-LVAD (n = 17) support. Of these, 5 miRs displayed a similar expression pattern among the devices (miR-129*, miR-146a, miR-155, miR-221, miR-222), whereas others only changed significantly during pf-LVAD (miR-let-7i, miR-21, miR-378, miR-378*) or cf-LVAD support (miR-137). In addition, 4 miRs were investigated in plasma of cf-LVAD supported patients (n = 18) and healthy controls (n = 10). Circulating miR-21 decreased at 1, 3, and 6 months after LVAD implantation. MiR-146a, miR-221 and miR-222 showed a fluctuating time pattern post-LVAD. Conclusion Our data show a different miR expression pattern after LVAD support, suggesting that differentially expressed miRs are partially responsible for the cardiac morphological and functional changes observed after support. However, the miR expression patterns do not seem to significantly differ between pf- and cf-LVAD implying that most cardiac changes or clinical outcomes specific to each device do not relate to differences in miR expression levels