Recent trials reported that risk of atrial fibrillation (AF) is increased in patients using ivabradine compared with controls. We performed this meta-analysis to investigate the risk of AF association with ivabradine treatment on the basis of data obtained from randomized controlled trials (RCTs). We searched PubMed, EMBASE, Scopus, and the Cochrane Library for RCTs that comprised >100 patients. The incidence of AF was assessed. We obtained data from European Medicines Agency (EMA) scientific reports for the RCTs in which the incidence of AF was not reported. We used trial sequential analysis (TSA) to provide information on when we had reached firm evidence of new AF based on a 15% relative risk increase (RRI) in ivabradine treatment. Three RCTs and 1 EMA overall oral safety set (OOSS) pooled analysis (included 5 RCTs) were included in the meta-analysis (N = 40 437). The incidence of AF was 5.34% in patients using ivabradine and 4.56% in placebo. There was significantly higher incidence of AF (24% RRI) in the ivabradine group when compared with placebo before (RR: 1.24, 95% confidence interval: 1.08-1.42, P = 0.003, I 1980 = 53%) and after excluding OOSS (RR: 1.24, 95% confidence interval: 1.06-1.44, P = 0.008). In the TSA, the cumulative z-curve crossed both the traditional boundary (P = 0.05) and the trial sequential monitoring boundary, indicating firm evidence for ≥15% increase in ivabradine treatment when compared with placebo. Study results indicate that AF is more common in the ivabradine group (24% RRI) than in controls.

IntroductionCoronary fractional flow reserve (FFR) is recommended as the gold standard method in evaluating intermediate coronary stenoses. However, there are significant debates concerning the agents and the timing of the measurement.AimTo compare the contrast medium induced Pd/Pa ratio (CMR) with the FFR.Material and methodsWe enrolled 28 consecutive patients with 34 intermediate lesions who underwent coronary FFR measurement by intracoronary (i.c.) adenosine. After baseline Pd/Pa was calculated, a single contrast medium (Iomeron) injection of 6 ml (3 ml/s) was performed manually. Within 10 s after the contrast medium injection, the CMR was calculated. Bolus injection of i.c. adenosine was performed to induce maximal hyperemia (from 60 µg to 600 µg), and when it was ≤ 0.80, the intermediate lesion was considered as significant.ResultsAfter bolus i.c. adenosine, 12 lesions of 34 (35.3%) were identified as significant. The CMR value was 0.86 ±0.06 (range: 0.71–0.97). There were no significant differences between FFR and CMR values (p = 0.108). A substantial positive correlation between adenosine and contrast values was detected (0.886 and p < 0.001). Good agreement in Bland-Altman analysis was revealed (mean bias was 0.027, 95% confidence interval 0.038–0.092). Receiver operating characteristics curve analysis showed 90.9% sensitivity and 91.7% specificity for a cut-off value of 0.85 for the CMR compared to FFR (≤ 0.80).ConclusionsOur study showed that measuring the CMR is a feasible method compared to FFR. The CMR may be used in situations where adenosine cannot be administered.

SummaryBackroundCoronary artery ectasia (CAE) without specific symptoms is the localised or diffuse swelling of the epicardial coronary arteries. Magnessium (Mg) plays an important role in cardiac excitability, vascular tonus, contractibility, reactivity and vasodilatation. In our research, we aimed to study the vasodilatory effect of Mg in the aetiopathogenesis of ectasia.MethodsPatients identified during routine coronary angiograms in our clinic between January 2010 and 2013 were included in the study. Sixty-two patients with isolated CAE, 57 with normal coronary angiograms (NCA), 73 with severe coronary artery disease (CAD), and 95 with stenosis of at least one coronary artery and CAE (CAD + CAE) were included in the study. Serum Mg levels were measured in mg/ dl after 12 hours of fasting.ResultsThere were no statistically significant differences between the groups in terms of age, hypertension, smoking, hyperlipidaemia, diabetes mellitus, family history of coronary artery disease and medications used. Serum glucose, thyroid stimulating hormone (TSH), urea, total cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol, sodium and potassium levels were similar in all groups. Serum Mg levels were 1.90 ± 0.19 mg/dl in patients with isolated CAE, 1.75 ± 0.19 mg/dl in those with CAD, 1.83 ± 0.20 mg/dl in those with CAD + CAE, and 1.80 ± 0.16 mg/dl in the NCA group. These results show that Mg levels were higher in ectasia patients with or without CAD.ConclusionsThe histopathological characteristics of patients with CAE were similar to those with CAD. The specific mechanism of abnormal luminal dilatation seen in CAE however remains to be elucidated. Mg is a divalent cation with powerful vasodilatory effects. In our study, serum Mg levels were found to be statistically higher in ectasia patients with or without CAD.

Objective:Urocortin 1 (UCN1) has vasodilator, diuretic, and natriuretic effects, and its expression increases in heart failure (HF). Adrenomedullin (ADM) increases cardiac output and lowers blood pressure in healthy men and in patients with heart failure. The aim of the study was to determine UCN1 and ADM levels in patients with HF, to evaluate the relationship of UCN1 and ADM with various clinical parameters, and to assess UCN1 and ADM as diagnostic markers in HF, in comparison with pro-brain natriuretic peptide (pro-BNP).Methods:We investigated serum levels of UCN1, ADM, and pro-BNP in 86 consecutive patients with systolic HF [ejection fraction (EF) ≤45%] and 85 healthy controls. Serum UCN1, ADM, and pro-BNP levels were measured with the ELISA method. Transthoracic echocardiography was performed to determine left ventricular EF and pulmonary artery systolic pressure.Results:UCN1 and ADM levels were higher in HF patients (446.2±145.7 pg/mL, p<0.001; 87.9±4.2 pg/mL, p<0.001 respectively). UCN1 was positively correlated with pro-BNP (r=0.963, p<0.001), ADM (r=0.915, p<0.001), and NYHA (r=0.879, p<0.001); ADM was positively correlated with pro-BNP (r=0.956, p<0.001) and NYHA (r=0.944, p<0.001). Receiver operating characteristic curves yielded an area under the curve of 1.00 (p<0.001) for UCN1, 1.00 (p<0.001) for ADM, and 0.99 (p<0.001) for pro-BNP in the diagnosis of HF.Conclusion:UCN1 and ADM increase with worsening HF and left ventricular dysfunction. They may be used as diagnostic biomarkers in systolic HF, but the incremental value of measuring UCN1 and ADM in patients tested for pro-BNP is questionable.

In this study, the aim is to investigate the prevalence of various coronary artery anomalies (CAAs), evaluated by 256-detector row coronary computed tomography (CCT), within the Turkish population. Materials and methods:We included 2973 patients who had received CCT. The high take-off right coronary artery (RCA) and left coronary artery (LCA), the RCA arising from the left sinus (LS), the LCA arising from the right sinus (RS), the circumflex artery (CX) arising from the RS, the single coronary ostium originating from the RS, the CX arising from the RCA, and the RCA arising from the pulmonary artery were evaluated.Results: Seventy-nine patients (2.65%) were diagnosed with CAAs. The frequency of high take-off of the RCA, LCA, and both was 0.1%, 0.67%, and 0.06%, respectively. Frequency of separate ostium of the left anterior descending artery and CX was 0.67%. The frequency of RCA originating from the LS, CX originating from the RS, LCA originating from the RS, LCA and RCA originating from the pulmonary artery, and CX originating from the RCA was 0.50%, 0.10%, 0.23%, 0.03%, and 0.20%, respectively. Conclusion:In this study, CCT was demonstrated to be a high-quality imaging modality for the detection of CAAs.