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Background: Radiofrequency catheter ablation (RFCA) is increasingly performed for the treatment of atrial fibrillation (AF), but it is problematic because the use of anti-arrhythmic agents is largely restricted in patients undergoing hemodialysis (HD) therapy. However, little is known about the long-term clinical outcomes of AF after RFCA in HD patients., Methods: Between 2002 and 2008, 16 HD patients (age: 63.8 ± 7.4 years, 75.0% men) underwent RFCA for AF at the Toyota Kosei Hospital. We investigated the long-term results and mortality of RFCA for AF in HD patients and compared them with those of 111 non-HD patients (age: 58.6 ± 10.0 years, 78.3% male) who received the same procedures., Results: During the follow-up (64.3 ± 25.4 months in HD patients, 70.5 ± 20.2 months in non-HD patients) after the initial RFCA procedure, sinus rhythm was restored in 4 HD patients (25%) and in 45 non-HD patients (40.5%). Multiple procedures were performed in 12 HD patients and in 57 non-HD patients. After the final procedure, 13 HD patients (81.3%) and 92 non-HD patients (82.9%) were free of atrial arrhythmia and symptoms. Of importance, Kaplan-Meier analysis did not demonstrate any significant differences in the atrial arrhythmia-free rate after the last procedure between HD patients and the control group matched after propensity-score analysis despite higher all-cause mortality in HD patients than in non-HD patients., Conclusions: During 5-years of follow-up, the use of multiple RFCA procedures for AF in patients undergoing HD was favorable, whereas the use of a single procedure was disappointing. Multiple RFCA procedures can be an efficient approach to the treatment of AF in HD patients.

Background: Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine and biomarker that is produced after myocardial infarction and that is related to prognosis in acute coronary syndrome (ACS). We hypothesized that secreted proteins that activate GDF15 production may represent new ACS biomarkers., Methods: We expressed clones from an infarcted mouse heart cDNA library in COS1 cells and assayed for activation of a luciferase reporter gene controlled by a 642-bp fragment of the mouse growth differentiation factor 15 (GDF15) gene promoter. We measured the circulating concentrations of follistatin-like 1 (FSTL1) and GDF15 in 1369 patients with ACS., Results: One cDNA clone that activated the GDF15 promoter-luciferase reporter encoded the secreted protein FSTL1. Treatment with FSTL1 activated GDF15 production in cultured cardiomyocytes. Transgenic production of FSTL1 stimulated GDF15 production in the murine heart, whereas cardiomyocyte-selective deletion of FSTL1 decreased production of GDF15 in cardiomyocytes, indicating that FSTL1 is sufficient and required for GDF15 production. In ACS, FSTL1 emerged as the strongest independent correlate of GDF15 (partial R(2) = 0.26). A total of 106 patients died of a cardiovascular cause during a median follow-up of 252 days. Patients with an FSTL1 concentration in the top quartile had a 3.7-fold higher risk of cardiovascular death compared with patients in the first 3 quartiles (P < 0.001). FSTL1 remained associated with cardiovascular death after adjustment for clinical, angiographic, and biochemical variables., Conclusions: Our study is the first to use expression cloning for biomarker discovery upstream of a gene of interest and to identify FSTL1 as an independent prognostic biomarker in ACS.

Aims: Identification of arrhythmogenic pulmonary veins (PVs) initiating atrial fibrillation is helpful for catheter ablation. The aim of this study was to examine the possibility to recognize the arrhythmogenic PV using Holter ECG., Methods and Results: In 20 patients, P-wave characteristics were studied during pacing from four PVs. Holter ECG was recorded using two leads: the modified CC5 (Lead 1) and NASA (Lead 2), and the P-wave amplitude and duration were evaluated. In Lead 1, P-waves produced by left PV pacing were significantly lower in amplitude than right PV pacing (-3 +/- 75 vs. 86 +/- 43 microV, P < 0.001). In Lead 2, pacing in superior PVs produced P-waves with higher amplitude than inferior PVs (210 +/- 74 vs. 125 +/- 66 muV, P < 0.001). The criteria proposed by the morphological characteristics of P-waves identified putative arrhythmogenic PVs with an accuracy of 78%., Conclusion: It might be possible to identify putative arrhythmogenic PVs by modified Holter ECG recording.

Aims: This study investigated the potential association between homocysteine levels and cardiovascular events or atrial fibrillation (AF) recurrence following radiofrequency catheter ablation (RFCA) in patients with AF., Methods and Results: Blood samples were obtained prior to the RFCA procedure. Levels of homocysteine and carboxy-terminal telopeptide of collagen type I (CITP), a collagen type I degradation marker, were measured in 96 patients receiving RFCA; 62 paroxysmal or persistent AF patients and 34 paroxysmal supra-ventricular tachycardia patients. Patients were followed up for 2.1 +/- 1.5 years. Plasma homocysteine levels were significantly higher in patients with persistent AF (P < 0.05) compared with levels in paroxysmal AF and control patients. Homocysteine levels also positively correlated with left atrial dimension (LAD) (P < 0.01) and CITP levels (P < 0.001). While no significant correlation was found between basal homocysteine levels and recurrent AF after RFCA in AF patients, patients in the high homocysteine group exhibited a significantly higher rate of cardiovascular events without AF recurrence compared with those in the low homocysteine group (P < 0.05)., Conclusion: High homocysteine levels are associated with the presence of persistent AF, which is accompanied by increased CITP levels and LAD. Also confirmed is the role of homocysteine as a risk factor for the pathogenesis of cardiovascular events after RFCA in AF patients. Measurement of homocysteine level may provide useful information for the managing cardiovascular risk in patients with AF.

Aims: We assessed the effects of cardiac re-synchronization therapy (CRT) in patients who developed otherwise unexplained heart failure (HF) during right ventricular apical (RVA)-pacing for acquired complete atrioventricular block (CAVB)., Methods and Results: Eighteen consecutive CAVB patients with HF during RVA-pacing were assessed with haemodynamic studies immediately and 12 months after CRT-upgrade. Ten patients had idiopathic CAVB and 13 showed normal left ventricular (LV) function at RVA-pacemaker implantation. HF developed after 81 +/- 10 months. RVA-pacing duration correlated (r = 0.49, P < 0.05) with LV ejection fraction (LVEF) deterioration. Biventricular- (BiV) and LV-pacing acutely improved the systolic function comparably, but only BiV improved diastolic function. One-year post-CRT-initiation, New York Heart Association classification improved 35 +/- 3% (P < 0.05) and the number of hospitalizations decreased 85 +/- 3% (P < 0.0001). CRT decreased LV end-diastolic diameter (LVEDd) 7 +/- 2% (P < 0.01) and increased LVEF by 23 +/- 7% (P < 0.01). The CRT-induced reduction in LVEDd tended to be greater in patients with RVA-pacing for < 5 years vs. > 5 years (7.7 +/- 2.5 vs. 3.6 +/- 1.0 mm, P = 0.08)., Conclusion: CRT-upgrade improves the cardiac function and symptoms in CAVB patients with HF progression related to RVA-pacing. Because adverse LV-remodelling may be partly irreversible, consideration should be given to BiV- and LV-pacing upgrade as soon as possible after the indications appear, and prospective studies of the optimal timing of CRT-upgrade may be useful.