Kadir Uğur Mert

PRescriptiOn PattERns of Oral Anticoagulants in Nonvalvular Atrial Fibrillation (PROPER study)

Introduction: Inappropriate use of oral anticoagulants (OACs) have not been well investigatedand, however, may be frequent in real-world practice in patients with nonvalvular atrial fibrillation (NVAF). This study was designed to evaluate the prescription patterns and appropriateness of OACs in patients with NVAF in real-world clinical settings. Methods: We performed a prospective, observational study (NCT02366338). A total of 148 patients with NVAF were screened for OAC prescription. Appropriateness of prescribing was evaluated using 9 criteria of the Medication Appropriateness Index (MAI): indication, choice, dosage, modalities and practicability of administration, drug–drug interactions, drug–disease interactions, duplication, and duration. For each criterion, the evaluator has to rate whether the medication is (A) appropriate, (B) inappropriate but with limited clinical importance, and (C) inappropriate. Results: Of 148 patients, 73 (50%) were on warfarin (group 1), 39 (26%) were on rivaroxaban (group 2), and 36 (24%) were on dabigatran therapy (group 3). The MAI showed that 83% of group 1, 28% of group 2, and 47% of group 3 patients had at least 1 inappropriate criterion. Moreover, according to the choice criterion, 37% of group 1, 8% of group 2 and 5% of group 3 were rated as inappropriate, and dosage was not appropriate in 77% of group 1, 23% of group 2, and 42% of group 3. Conclusion: Inappropriate drug use is frequent among patients with NVAF not only for warfarin but also for NOACs. Although there is an apparent improvement in thromboprophylaxis of NVAF, much more effort is needed for appropriate use of OACs.

Effects of ivabradine and beta-blocker therapy on dobutamine-induced ventricular arrhythmias

BACKGROUND Indirect evidences suggest that the If blocker ivabradine may exert an antiarrhythmic effect in ventricular myocardium in heart failure (HF) patients by inhibiting spontaneous depolarisations, but the clinical relevance of this mechanism is not known. Dobutamine (DOB) has been known to increase heart rate and the incidence of cardiac arrhythmias. AIM In this study, we evaluated the effects of ivabradine on DOB-induced ventricular arrhythmias and compared them with those of beta-blocker (BB) therapy. METHODS Patients with decompensated HF requiring inotropic support, left ventricular ejection fraction < 35%, and in sinus rhythm were included in the study (ivabradine group - 29 patients, control group - 29 patients, BB group - 15 patients). All patients underwent Holter recording for 6 h before the initiation of DOB infusion. Following baseline recording, DOB was administered at incremental doses of 5, 10, and 15 μg/kg/min, with 6-h steps. Holter monitoring was continued during 18 h of DOB infusion and analysed for the median number of ventricular premature contractions (VPC), ventricular couplets, episodes of non-sustained ventricular tachycardia, and total ventricular arrhythmias in each step of the study protocol. RESULTS The positive chronotropic effect of incremental DOB doses was blunted by beta-blockade and was totally abolished by ivabradine. The median number of VPCs, ventricular couplets, and total ventricular arrhythmias significantly increased with incremental doses of DOB in the control group (p = 0.018) and, to a lesser extent, in the ivabradine group (p = 0.015). In the BB group the absolute VPCs numbers were smaller than in the control or the ivabradine group, with the on-ivabradine VPCs numbers falling between those seen in control and BB groups. A numeric increase in VPCs with incremental DOB doses occurred in the BB group but did not reach statistical significance (p > 0.05), consistent with a protective effect of beta-blockade. Ivabradine reduced VPCs by 43% at 5 μg/kg/min DOB and by 38% at 10 μg/kg/min DOB against the control group (VPCs median 256 vs. 147 and 251 vs. 158) in the absence of significant differences at 15 μg/kg/min DOB between the control and ivabradine groups (overall p > 0.05). Thus, ivabradine administered without background beta-blockade attenuated the arrhythmogenic effect of increasing doses of DOB in the low and moderate DOB dose but not in the high DOB dose. CONCLUSIONS In patients with decompensated HF, ivabradine appears to reduce the incidence of VPCs in response to low and medium DOB dose. Whether the anti-arrhythmic effect of ivabradine is additive to the anti-arrhythmic effect of beta-blockade requires further investigation; this should also determine the clinical significance of ventricular arrhythmia attenuation with ivabradine.

Effects of creatine supplementation on cardiac autonomic functions in bodybuilders: MERT et al .

Bodybuilder‐type workouts may affect heart rate variability (HRV), which has considerable potential to assess the role of autonomic nervous system (ANS). A scientifically designed approach is necessary for bodybuilders to achieve better results while protecting their health. In this study, we aimed to investigate HRV parameters in bodybuilders compared to healthy control subjects and effects of creatine supplementation. A total of 48 male participants (16 controls, 16 supplement (–), 16 supplement (+)) were evaluated in our study. Bodybuilders who were taking creatine supplementation were enrolled in supplement (+) group. HRV parameters were measured from 24‐hour Holter recordings of all participants.

Guideline-adherent therapy for stroke prevention in atrial fibrillation in different health care settings: Results from RAMSES study

OBJECTIVE No studies have been conducted in Turkey to compare the quality of stroke prevention therapies provided in different healthcare settings in patients with atrial fibrillation (AF). Therefore, we aimed to evaluate possible differences between secondary (SH) and tertiary hospital (TH) settings in the effectiveness of implementing AF treatment strategies. METHODS Baseline characteristics of 6273 patients with non-valvular AF enrolled in the RAMSES (ReAl-life Multicentre Survey Evaluating Stroke Prevention Strategies in Turkey) study were compared. RESULTS Of the study population, 3312 (52.8%) patients were treated in THs and 2961 (47.2%) patients were treated in SHs. Patients treated in the SH setting were older (70.8±9.8 vs. 68.7±11.4years, p<0.001), had a lower socioeconomic status, had a higher CHA2DS2VASc and HASBLED scores (3.4±1.4 vs. 3.1±1.7, p<0.001 and 1.7±1.0 vs. 1.6±1.1, p<0.001 respectively), and had more comorbidities than patients treated in THs. Inappropriate oral anticoagulant use was more prevalent in SHs than THs (31.4% vs. 25.6%, p<0.001). When over- and undertreatment rates were compared among hospital types, overtreatment was more prevalent in THs (7.6% vs. 0.9%, p<0.001) while undertreatment was more common in SHs (30.5% vs. 17.9%, p<0.001). CONCLUSION This study demonstrates the marked disparity between patient groups with AF presenting at SHs and THs. The use of guideline-recommended therapy is not adequate in either type of centre, overtreatment was more prevalent in THs and undertreatment was more prevalent in SHs.

Cutaneous microvascular reactivity and aortic elasticity in coronary artery disease: Comparison of the laser Doppler flowmetry and echocardiography

BACKGROUND AND AIM Decreased vascular reactivity in atherosclerosis was previously shown. In our study, it was aimed to demonstrate the decreased vascular functions in both microvascular and macrovascular tissues and to estimate any correlation between them. METHODS Twenty-five control outpatients with no coronary artery disease (CAD) history and 26 outpatients with CAD history were enrolled in the study. Local cutaneous post-occlusive reactive hyperemia (PORH) responses after three minutes of brachial occlusion with a pneumatic cuff were recorded noninvasively by a Perimed Periflux 5010 laser Doppler flow system. Aortic distensibility and stiffness indexes were recorded noninvasively by a two-dimensional Doppler echocardiography machine (Vivid S6 GE Medical System, Horten, Norway). RESULTS Except for the medication history of subjects, there were no significant demographic differences between the CAD and control groups. Peak flow (PF), resting flow (RF) and biological zero(BZ) laser Doppler measurements were not decreased, but PF-RF/RF (%), PF-BZ/BF (%), hyperemia repayment and PORH indexes were significantly decreased in the CAD group (P=0.005, P=0.024, P=0.017, P=0.006, respectively) with laser Doppler measurements. Aortic strain (%) and aortic distensibility (cm3/dyn-1) measurements were significantly decreased in the CAD group (P=0.005, P=0.013). However, there was no correlation between microvascular indexes (hyperemia repayment index, PORH index) and macrovascular indexes (aortic strain and aortic distensibility). DISCUSSION Different corrupted vascular tonus regulator systems in arteries of varying diameter, different major reactive responses to the stimuli or, finally, the lack of a number of subjects to obtain a significant level may be responsible for the irrelevant correlation analysis. CONCLUSION The differences in arterial beds (both aorta and microcirculation) may be examined to assess the cardiovascular risk in patients with history of CAD.

Ivabradine in cardiogenic shock: Fact or fiction?

We read with great interest the recent article by Bonadei et al. documenting the role ivabradine in a patient with cardiogenic shock.1 Although management of the patient was successful, we want to address some points that merit more attention. Cardiogenic shock usually presents with low systolic blood pressure and clinical signs of hypoperfusion. Hypoperfusion causes release of catecholamines, which increase contractility and peripheral blood flow, but also increase myocardial oxygen demand and have proarrhythmic and myocardiotoxic effects.2 Next to an early revascularization strategy and optimal drug therapy including vasopressors and positive inotropic agents, intraaortic baloon pump (IABP) is considered as an additional option to achieve initial hemodynamic stabilization and improve clinical outcome. Inotropic agents and vasoconstrictors temporarily improve cardiac output and peripheral perfusion but do not interrupt vicious circle.2,3 Rapid IABP support may temporarily relieve ischemia and support the circulation. Relief of coronary occlusion interrupts the vicious circle and results better hemodynamic response like increase in blood pressure and decrease in heart rate.3 In the current case report the heart rate of the patient decreased from 130 bpm to 105 bpm after successful intervention (left main coronary artery stenting and IABP) and administration of furosemide. However, heart rate reduction after 48 h of ivabradine therapy was higher than the clinical trials’ results (105 bpm to 80 bpm). For instance, after 1 month of ivabradine therapy, an uncorrected heart rate reduction was 15 bpm in the SHIfT trial, and 13 bpm in the INTENSIfY trial.4,5 Therefore, we think that, the reduction of the heart rate is an expected result of clinical stabilization, IABP support, and decompensation after diuretic therapy rather than an ivabradine effect. Cavusoglu et al have recently shown in a randomized, placebo-controlled trial that the dobutamine induced increase in heart rate was blunted by ivabradine treatment in patients hospitalized with acute decompensated heart failure.6 After dobutamine administration at incremental doses of 5, 10 and 15 mg/kg/min, dose dependent increase in heart rate was 5 bpm, 13 bpm, 18 bpm, respectively in the control group of their study population. However, in this study there is no data on the dosage of inotropics and early effects of ivabradine in heart rate reduction.

Questioning reliability of observational study: MERT et al .

The authors greatly appreciate Cekic et al. for their insightful comments with regard to our manuscript titled “Effects of creatine supplementation on cardiac autonomic functions in bodybuilders.”1 In this study, we aimed to investigate heart rate variability (HRV) parameters of cardiac autonomic functions in bodybuilders compared to healthy control subjects and evaluate effects of creatine supplementation on HRV parameters. The study was designed as a cross-sectional study which is a type of observational study usually usedwhen a randomized controlled trials or cohort study is going to be difficult. Furthermore, evaluation of HRV in the Holter recordings yields a useful index of cardiac autonomic functions.2 We take a “snapshot” of autonomic functions by using Holter recordings in this reliable methodology. Unlike the experimental design, cross-sectional designs focus on studying and drawing inferences from existing differences between cases. Undoubtedly, there is no methodological mistake in our observational study. However, it is difficult to determine whether the outcome followed exposure in time or exposure resulted from the outcome with cross-sectional design.3 Hence, it was clearly demonstrated as an attenuation of vagal dominance in HRV as a result of supplementation but this cannot be distinguished from the effects of overtraining syndrome. As it was mentioned in the limitation part of the article,1 the study can be more durable with the prospective evaluation of supplementation quantity, overtraining parameters, athletic conditioning levels, and exercise intensity of each individual. Majority of bodybuilders take supplements based on the belief that their performance will improve, without proven scientific evidence or anymedical support. Further studies with prospectively well-designed protocol are needed to settle a scientifically designed approach for bodybuilders to achieve better results while protecting their health.

Evaluation of Increase in Intraventricular Gradient and Dynamic Obstruction During Exercise-Stress Test in Competetive Runners

OBJECTIVE Sudden cardiac death in athletes is one of the most tragic health events seen both in our country and all over the world. In some of those athletes, there is no obvious structural abnormality. Dynamic changes in intracardiac hemodynamics during exercise may be a cause for sudden death in these athletes, the impact of exercise on intracardiac gradient and cardiac hemodynamic parameters in athletes was compared with healthy controls. METHODS A total of 21 professional male athletes and 21 healthy male controls were included in the study. Transthoracic echocardiography was performed in all participants both at rest and maximal exercise level to assess the intraventricular gradient (IVG) and cardiac systolic and diastolic functions. Abnormal IVG was defined as gradient of >30 mm Hg at peak exercise level. RESULTS Both groups reached the level of predicted maximum exercise. There was no exercise limiting symptom among participants during exercise test. The athletes revealed a higher maximum peak systolic IVG at baseline and after exercise in comparison with the control group. None of the participants showed an abnormal IVG level. CONCLUSION Our results showed that there was no dynamic intraventricular obstruction with aerobic exercise in subjects with a structurally normal heart.

Rationale, design, and methodology of the Evaluation of Perceptions, Knowledge, and Compliance with the Guidelines in Real Life Practice: A Survey on the Under-treatment of Hypercholesterolemia

OBJECTIVE A wide gap exists between dyslipidemia guidelines and their implementation in the real world, which is primarily attributed to physician and patient compliance. The aim of this study is to determine physician and patient adherence to dyslipidemia guidelines and various influential factors. METHODS The Evaluation of Perceptions, Knowledge, and Compliance with the Guidelines in Real Life Practice: A Survey on the Under-treatment of Hypercholesterolemia (EPHESUS) trial (ClinicalTrials.gov number NCT02608645) will be an observational, multicenter, non-interventional study. The study targets enrollment of 2000 patients from 50 locations across Turkey. All of the data will be collected in a single visit and current clinical practice will be evaluated. A cross-sectional survey of public perception and knowledge of cholesterol treatment among Turkish adults will be performed. All consecutive patients admitted to cardiology clinics who are in the secondary prevention group (coronary heart disease, peripheral artery disease, atherosclerotic cerebrovascular disease) and who are in the high-risk primary prevention group (type 2 diabetes mellitus with no prior known coronary heart disease; patients who had markedly elevated single risk factors, in particular, cholesterol >8 mmol/L [>310 mg/dL], blood pressure ≥180/110 mmHg, a calculated Systematic Coronary Risk Evaluation [SCORE] ≥5%, or <10% 10-year risk of fatal cardiovascular disease) will be included. Demographic, lifestyle, medical, and therapeutic data will be collected with a survey designed for the study. CONCLUSION The EPHESUS registry will be the largest study conducted in Turkey evaluating the adherence to dyslipidemia guidelines both in secondary and high-risk primary prevention patients.

Electromagnetic interference of mobile phones: insight into heart rate variability

We read with great interest the recent article by Ekici et al. (1) entitled “The effects of the duration of mobile phone use on heart rate variability parameters in healthy subjects” published in Anatol J Cardiol 2016; 16: 833-8, documenting the role of mobile phone (MP) use in healthy subjects. Although it is an original concept, we want to address some points that merit more attention. The rate at which energy is absorbed by the human body is measured by the specific absorption rate (SAR). As authors mentioned in the limitations section, the SAR values were not analyzed. Therefore, the statistical analyses could be affected by different MP models used in this study. Moreover, MP is a potential source of electromagnetic field (EMF) that can affect the reliability of medical devices. The electromagnetic interference (EMI) on medical devices by MP depends on various factors, including power emitted by MP, the frequency of operation, the distance between MP and the medical device, mode of operation of MP, and the immunity of the medical device concerned (2). Furthermore, there is compelling evidence that MPs may produce EMI that adversely affects the operation of ECG systems and may lead to the inability to properly interpret ECG results (3). Ekici et al. (1) used 24-h Holter ECG records to evaluate the heart rate variability (HRV). HRV is commonly defined by the standard deviation of intervals between successive R waves of the cardiac cycle. The distance between the medical device and MP during ECG recording of the patient alters the QRS complexes (4). The data are presumably uncorrected for type and proximity of MP. Thus, it is extremely difficult to evaluate the results without any interference on Holter monitoring due to MPs. On the other hand, some users of mobile handsets have reported feeling several unspecific symptoms during and after its use, such as fatigue, headaches, tachycardia, etc. All these symptoms can also be attributed to stress and that current knowledge cannot separate the symptoms from nocebo effects. Moreover, cardiac-vagal spectral component of HRV may be sensitive to the recent experience of emotional stress (5). Increased environmental stress can make people use their MPs more often than usual and increased number of telephone calls can also cause stress. Therefore, it is difficult to isolate the leading cause of HRV differentiation in the study. Nowadays, MPs are being used not only for calling but also for other services, such as text messaging, email, internet access, video communication, gaming, listening to music, photography, and watching movies, etc. At the same time, MP emits a peak amount of power not only during the ringing phase but also during its standby mode (4). Calculation formula for daily durations of MP use only exists duration/number of telephone calls in the manuscript (1). Therefore, this calculation cannot reflect the EMF exposure in this study population. Overall, it is an uneasy piece of work that performing this type original clinical research is extremely challenging. Data could be interrupted by several interfering environmental electromagnetic pollution these days. Further randomized studies are recommended with more clear protocols.