Association between left atrial low-voltage area and induction and recurrence of macroreentrant atrial tachycardia in pulmonary vein isolation for atrial fibrillation.

BACKGROUND: The relationship between induction and recurrence due to atrial tachycardia (AT) and left atrial (LA) matrix progression after atrial fibrillation (AF) ablation remains unclear. METHODS: One hundred fifty-two consecutive patients with paroxysmal and persistent AF who underwent pulmonary vein isolation (PVI) and cavo-tricuspid isthmus (CTI) ablation and achieved sinus rhythm before the procedure were classified into three groups according to the AT pattern induced after the procedure: group N (non-induced), F (focal pattern), and M (macroreentrant pattern) in 3D mapping. RESULTS: The total rate of AT induction was 19.7% (30/152) in groups F (n = 13) and M (n = 17). Patients in group M were older than those in groups N and F, with higher CHADS2/CHA2DS2-VASc values, left atrial enlargement, and low-voltage area (LVA) size of LA. The receiver operating characteristic curve determined that the cut-off LVA for macroreentrant AT induction was 8.8 cm2 (area under the curve [AUC]: 0.86, 95% confidence interval [CI]: 0.75-0.97). The recurrence of AT at 36 months in group N was 4.1% (5/122), and at the second ablation, all patients had macroreentrant AT. Patients with AT recurrence in group N had a wide LVA at the first ablation, and the cut-off LVA for AT recurrence was 6.5 cm2 (AUC 0.94, 95%CI 0.88-0.99). Adjusted multivariate analysis showed that only LVA size was associated with the recurrence of macroreentrant AT (odds ratio 1.21, 95%CI 1.04-1.51). CONCLUSIONS: It is important to develop a therapeutic strategy based on the LVA size to suppress the recurrence of AT in these patients.

Effect of the Xanthine Oxidase Inhibitor, Febuxostat, on WBC Count in Asymptomatic Hyperuricemia: Subanalysis of the Randomized PRIZE Study.

AIMS: The anti-inflammatory effects of the xanthine oxidase inhibitor, febuxostat, a urate-lowering agent, have been reported in animal studies. However, the anti-inflammatory effects of urate-lowering therapy and its associated cardiovascular protective effects have not been fully determined in actual clinical practice. This study aimed to investigate the effect of febuxostat on white blood cell (WBC) count in patients with asymptomatic hyperuricemia and to assess for potential correlations between changes in WBC count and inflammatory biomarkers and atherosclerosis in this patient population. METHODS: This was a post hoc subanalysis of the PRIZE study, a multicenter, prospective, randomized, open-label clinical trial. In the PRIZE study, asymptomatic hyperuricemia patients were randomized to febuxostat group or control group with non-pharmacological therapy and evaluated the effect on vascular. The primary endpoints of this study were the assessment of the time course of WBC count over 24 months and its changes from baseline. Correlations of WBC count with high-sensitivity C-reactive protein (hs-CRP) and mean common carotid artery (CCA)-IMT were also exploratorily examined in the febuxostat group. RESULTS: A total of 444 patients (febuxostat group, n=223; control group, n=221) with WBC measurements available at baseline and at least one of the follow-up time points of 12 or 24 months, were enrolled. Febuxostat modestly, but significantly, reduced WBC counts at 12 and 24 months compared with the baseline levels (P=0.002 and P=0.026, respectively). Notably, the WBC count in the febuxostat group at 12 and 24 months was significantly lower than that in the control group (P=0.007 and P=0.023, respectively). The changes in WBC count were associated with those of hs-CRP (P=0.038), but not with CCA-IMT (P=0.727). CONCLUSIONS: Febuxostat therapy for 24 months modestly, but significantly, decreased WBC count in patients with asymptomatic hyperuricemia. This might potentially reflect a modest anti-inflammatory action of febuxostat in clinical settings.

DAPagliflozin for the attenuation of albuminuria in Patients with hEaRt failure and type 2 diabetes (DAPPER study): a multicentre, randomised, open-label, parallel-group, standard treatment-controlled trial.

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the urinary albumin-to-creatinine ratio (UACR) in patients with elevated levels of albuminuria in the presence or absence of heart failure (HF) or type 2 diabetes mellitus (T2D). However, these effects have not yet been reported in the presence of both HF and T2D. This lack of evidence prompted us to conduct a clinical trial on the effects of dapagliflozin on UACR in patients with HF and T2D. Methods: DAPPER is a multicentre, randomised, open-labeled, parallel-group, standard treatment-controlled trial that enrolled patients at 18 medical facilities in Japan. Eligible participants with both HF and T2D and aged between 20 and 85 years were randomly assigned to a dapagliflozin or control (anti-diabetic drugs other than SGLT 2 inhibitors) group with a 1:1 allocation. The primary outcome was changes in UACR from baseline after a two-year observation, and secondary endpoints were cardiovascular (CV) events and parameters related to HF. This trial was registered with the UMIN-CTR registry, UMIN000025102 and the Japan Registry of Clinical Trials, jRCTs051180135. Findings: Between 12 May 2017 and 31 March 2020, 294 patients were randomly assigned to the dapagliflozin group (n = 146) or control group (n = 148). The mean age of patients was 72.1 years and 29% were female. The mean glycated hemoglobin value was 6.9%, mean NT-proBNP was 429.1 pg/mL, mean estimated GFR was 65.7 mL/min/1.73 m2, and median UACR was 25.0 (8.8-74.6) mg/g Cr in the dapagliflozin group and 25.6 (8.2-95.0) mg/g Cr in the control group. Of the 146 patients in the dapagliflozin group, 122 completed the study, and 107 (87.7%) were taking 5 mg of dapagliflozin daily at the end of the observation period. The primary outcome did not significantly differ between the dapagliflozin and control groups. Among the secondary endpoints, the mean decrease in left ventricular end-diastolic dimensions as one of the echocardiographic parameters was larger in the dapagliflozin group than in the control group. The composite endpoint, defined as CV death or hospitalisation for CV events, hospitalisation for HF events, hospitalisation for all causes, and an additional change in prescriptions for heart failure in a two-year observation, was less frequent in the dapagliflozin group than in the control group. Interpretation: Although dapagliflozin at a dose of 5 mg daily did not reduce urinary albumin excretion in patients with HF and T2D from that in the controls, our findings suggest that dapagliflozin decreased CV events and suppressed left ventricular remodeling. Funding: AstraZeneca KK, Ono Pharmaceutical Co., Ltd.