Safety of once- or twice-daily dosing of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with nonvalvular atrial fibrillation: A NOAC-TR study.

Once-daily dosing of non-vitamin K antagonist oral anticoagulants (NOACs) may increase patient adherence to treatment but may also be associated with a higher risk of bleeding. In this study, we investigated the adherence to once- or twice-daily dosing of NOACs and the risk of bleeding in nonvalvular atrial fibrillation (NVAF) patients. This multicenter cross-sectional study, conducted between 1 September 2015 and 28 February 2016, included 2214 patients receiving NOACs for at least 3 months, due to NVAF. Patients receiving once-daily or twice-daily NOAC doses were 1:1 propensity score matched for baseline demographic characteristics and the presence of other diseases. The medication adherence was assessed by the 8-item Morisky Medication Adherence Scale. Risk factors were investigated in relation to minor and major bleeding. The mean age of patients was 71 ± 10 years, and 53% of the patients were women. The medication adherence was lower in patients receiving twice-daily NOAC doses compared to once-daily-dose group (47% versus 53%, p = 0.001), and there was no difference between the groups in terms of minor (15% versus 16%, p = 0.292) and major bleeding (3% versus 3%, p = 0.796). Independent risk factors for bleeding were non-adherence to medication (OR: 1.62, 95% CI: 1.23-2.14, p = 0.001), presence of 3 or more other diseases (OR: 10.3, 95% CI: 5.3-20.3, p < 0.001), and HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile INR, Elderly, Drugs or alcohol) score (OR: 4.84, 95% CI: 4.04-5.8, p < 0.001). In summary, the once-daily dose of NOACs was associated with increased patient adherence to medication, while it was not associated with bleeding complications.

A Novel Index Combining Diastolic and Systolic Tissue Doppler Parameters for Prediction of Atrial Fibrillation Recurrence.

OBJECTIVE: Identification of patients at risk for atrial fibrillation (AF) recurrence with using simple and objective parameters may be helpful in tailoring the treatment. In this study, we investigated whether E/(Ea×Sa) and Ea/(Aa×Sa) could be a predictor of AF recurrence after cardioversion. (E = early diastolic transmitral velocity, Ea = early diastolic mitral annular velocity, Aa = late diastolic mitral annular velocity, Sa = systolic mitral annular velocity). METHODS: In total, 127 patients with persistent AF were evaluated for this study and 73 patients were included according to the study criteria. Sinus rhythm (SR) was achieved for 70 patients after electrical direct-current cardioversion. E, Sa, Ea, and Aa were determined at mitral medial and lateral site and average values obtained. E/(Ea×Sa) and Ea/(Aa×Sa) were calculated (medial, lateral, average). Heart rate and rhythm were followed with an electrocardiography (ECG) monitor and 12-lead ECG at first week and first month. RESULTS: At one month, 53 patients (75.7%) were in SR, whereas 17 patients (24.3%) reverted to AF. According to precardioversion E/(Ea×Sa) lateral, E/(Ea×Sa) medial, E/(Ea×Sa) average (P ≤ 0.01 for all the indices), 24-hour echocardiographic evaluation E/(Ea×Sa) lateral, E/(Ea×Sa) medial, E/(Ea×Sa) average, Ea/(Aa×Sa) lateral, Ea/(Aa×Sa) medial, and Ea/(Aa×Sa) average (P ≤ 0.01 for all the indices), indices were significantly higher in the AF recurrence group than in the SR group. Furthermore, the ROC analysis showed that all the E/(Ea×Sa) and Ea/(Aa×Sa) parameters predict the AF recurrence. The AUC values range from 70% to 81% (P ≤ 0.01 for all the parameters). In subgroup analysis of the patients, precardioversion mitral medial E/Ea ratio was between 8 and 15, and the ROC analysis showed that the novel indices predict the AF recurrence. The AUC values range from 72% to 86% (P ≤ 0.02 for all the parameters). CONCLUSIONS: We found that E/(Ea×Sa) and Ea/(Aa×Sa) indices are novel predictors of AF recurrence.

The effect of varenicline on Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio in healthy smokers and nonsmokers.

BACKGROUND: Varenicline could affect the T wave and QT interval. The interval from the peak to the end of the electrocardiographic (ECG) T wave (Tp-e) may correspond to the transmural dispersion of repolarization, and increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. In this study, we assessed the effects of varenicline on Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio. METHODS: Thirty healthy volunteers (15 healthy non-smokers [NS] and 15 healthy smokers [S]) were included in the randomized, double-blind, placebo-controlled, crossover study. Varenicline (2 mg single dose) or placebo was administered in two different testing sessions (5 days after the first period, performed the second period). Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio were assessed in the supine position and during handgrip exercise before and after the participants were given placebo or varenicline. Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio were calculated from continuous ECG recordings and averages were used in the final analysis. RESULT: There were no statistically significant differences among any of the Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio before and after placebo administration in both groups (S and NS). In the S group, Tp-e and QTc interval, and Tp-e/QT and Tp-e/QTc ratio were significantly increased after varenicline administration (Tp-e: 64.28 ± 8.78 vs. 70.42 ± ± 13.12; p = 0.02, QTc: 409.57 ± 28.17 vs. 425.28 ± 32.79; p = 0.02, Tp-e/QT: 0.18 ± 0.02 vs. 0.19 ± 0.03; p = 0.04, Tp-e/QTc: 0.17 ± 0.02 vs. 0.19 ± 0.02; p = 001) but these parameters were not changed in the NS group. CONCLUSIONS: Tp-e and QTc interval, and Tpe/QT and Tpe/QTc ratio were increased after varenicline administration in smokers.

Evaluation of plasma eosinophil count and mean platelet volume in patients with coronary slow flow.

OBJECTIVE: The pathophysiology of coronary slow flow has not been clearly defined, although multiple abnormalities including arteritis, endothelial dysfunction, and atherothrombosis, have been reported. It is known that eosinophils play an important role in inflammation, endothelial dysfunction, and thrombosis. We aimed to compare the eosinophil counts of coronary slow flow patients versus healthy controls. METHODS: This study included 50 coronary slow flow patients (19 males, mean age 65.6 ± 13.7 years) and 30 healthy controls (10 males, mean age 57.86 ± 11.6 years). These participants were evaluated using concurrent routine biochemical tests as well as neutrophil, lymphocyte, and eosinophil counts and mean platelet volume (MPV), which were obtained from the whole blood count. These parameters were compared between groups. RESULTS: The baseline characteristics of the study groups were comparable. The coronary slow flow patients had a higher mean platelet volume and eosinophil count than the control group (8.38 ± 0.86 vs 6.28 ± 1.6 fL and 0.31 ± 0.42 vs 0.09 ± 0.05; p<0.001 and 0.008, respectively). CONCLUSION: Our study demonstrated a relationship between eosinophil count and MPV in patients with coronary slow flow.

The relationship between serum bilirubin concentration and coronary slow flow.

BACKGROUND: The pathophysiology of coronary slow flow (CSF) has not been clearly identified, although multiple abnormalities including arteritis, endothelial dysfunction, and atherothrombosis have been reported. Several studies have demonstrated that higher serum bilirubin inhibits the inflammation and proliferation of vascular smooth muscle cells; in addition, there is a relationship between serum bilirubin and cardiovascular disease. However, the relationship between bilirubin and CSF is still unknown. In our study, we compared serum bilirubin concentrations between CSF patients and controls. METHODS: The study included 50 CSF patients (19 male, mean age 65.6 ± 13.7 years) and 30 controls (10 male, mean age 57.86 ± 11.6 years). Concurrent routine biochemical tests and leukocyte count, hemoglobin, hematocrit, and platelet count on whole blood count were performed in patients that underwent a coronary angiogram. These parameters were compared between groups. RESULTS: No statistically significant difference was found between the two groups in terms of basic characteristics. Total, direct, and indirect serum bilirubin levels were significantly lower among CSF patients than controls (14.0 ± 12.0 versus 6.15 ± 6.8, 5.6 ± 3.4 versus 2.6 ± 1.7, and 8.4 ± 8.5 versus 3.6 ± 3.4 µmol/l; all p < 0.001, respectively). CONCLUSIONS: The study revealed a relationship between serum bilirubin and CSF.

The effect of varenicline on heart rate variability in healthy smokers and nonsmokers.

Varenicline is an α4ß2 nicotinic acetylcholine receptor partial agonist. In this study, we assessed the effects of varenicline on heart rate variability (HRV). Thirty subjects were included in the randomized, double-blind, placebo-controlled, crossover study. Varenicline or placebo was administered in two different testing sessions. Time domain parameters and power spectral analysis of HRV were assessed in the supine position and during handgrip exercise before and after the participants were given placebo or varenicline. Fifteen healthy non-smokers (NS) and fifteen healthy smokers (S) were included in the study. There were no statistically significant differences among any of the time domain parameters obtained before and after placebo administration or between the S and NS groups with respect to varenicline administration. In frequency domain analyses, normalized HF (high-frequency) powers were significantly higher in the S group than in the NS group (before placebo, NS:6.57±3.58 vs. S:13.85±7.50, p=0.002, after placebo, NS:6.33±3.89 vs. S:10.82±4.88, p=0.007). After varenicline administration, the normalized HF power was significantly higher (NS:6.65±4.34 vs. S:11.06±4.52, p=0.01), and the ratio of LF (low-frequency) to HF was significantly lower (NS:8.44±5.89 vs. S:4.97±4.60, p=0.02) in the S group than in the NS group. Administration of a single dose of varenicline significantly increased the LF/HF ratio (5.83±2.69 vs. 8.44±5.89) in the NS group, but in the S group, there were no significant differences related to any of the time or frequency domain parameters. We concluded that a single dose of varenicline does not affect HRV in healthy smokers but that it may alter HRV when administered at a therapeutic dose to healthy non-smokers during mild sympathetic stimulation.