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QTc prolongation after ADHD medication.
Snircova, E, Marcincakova Husarova, V, Ondrejka, I, Hrtanek, I, Farsky, I, Nosalova, G
Neuro endocrinology letters. 2018;(8):549-554
Abstract
OBJECTIVE Multicenter studies have shown that cardiovascular risks of ADHD medication are extremely low. However, QTc length has been shown to be increased in smaller samples of patients or case reports after stimulant and atomoxetine medication. Based on recent studies of genetic polymorphisms associated with drug-induced QTc prolongation and polymorphisms linkage to regional populations, we hypothesized that the drug-induced QTc prolongation could be a factor of particular polymorphisms linked to specific regional populations undistinguished in multicenter studies. METHODS We included 69 patients from a region of central Slovakia, 36 patients were taking atomoxetine and 33 patients methylphenidate. QTc, heart rate, potassium levels and BMI were examined before and after 8 weeks of treatment. Therapeutic effect was measured by ADHD-RS-IV. RESULTS We found QTc prolongation after 8 weeks of treatment both with atomoxetine and methylphenidate that was neither followed by the significant changes in BMI and potassium levels nor the significant increase of heart rate. CONCLUSION This is the first study revealing QTc prolongation in the group of ADHD children from the same region after 8-week treatment with atomoxetine and methylphenidate, indicating the potential discrete abnormalities in cardiac functioning associated with polymorphisms in genes of dopaminergic and noradrenergic system.
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How Heart Rate Should Be Controlled in Patients with Atherosclerosis and Heart Failure.
da Silva, RMFL, Borges, ASR, Silva, NP, Resende, ES, Tse, G, Liu, T, Roever, L, Biondi-Zoccai, G
Current atherosclerosis reports. 2018;(11):54
Abstract
PURPOSE OF REVIEW Resting heart rate is an independent risk factor for all-cause and cardiovascular mortality in patients with heart failure. The main objectives are to discuss the prognosis of heart rate, its association with coronary atherosclerosis, and the modalities of control of the heart rate in sinus rhythm and in the rhythm of atrial fibrillation in patients with chronic heart failure. RECENT FINDINGS As a therapeutic option for control heart rate, medications such as beta-blockers, digoxin, and finally ivabradine have been studied. Non-dihydropyridine calcium channel blockers are contraindicated in patients with heart failure and reduced ejection fraction. The influence of the magnitude of heart rate reduction and beta-blocker dose on morbidity and mortality will be discussed. Regarding the patients with heart failure and atrial fibrillation, there are different findings in heart rate control with the use of a beta-blocker. Patients eligible for ivabradine have clinical benefits and increased ejection fraction. Vagal nerve stimulation has low efficacy for the control of heart rate. Complementary therapies such as tai chi and yoga showed no effect on heart rate. In this review, we discuss the main therapeutic options for the control of heart rate in patients with atherosclerosis and heart failure. More research is needed to examine the effects of therapeutic options for heart rate control in different population types, as well as their effects on clinical outcomes and impact on morbidity and mortality.
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QTc prolongation during ciprofloxacin and fluconazole combination therapy: prevalence and associated risk factors.
Berger, FA, Monadian, N, de Groot, NMS, Santbergen, B, van der Sijs, H, Becker, ML, Broers, AEC, van Gelder, T, van den Bemt, PMLA
British journal of clinical pharmacology. 2018;(2):369-378
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AIM(S): Ciprofloxacin and fluconazole combination therapy is frequently used as prophylaxis for, and treatment of, infections in patients with haematological malignancies. However, both drugs are known to prolong the heart rate-corrected QT (QTc) interval, which is a serious risk factor for torsade de pointes (TdP). Therefore, the aim of the current study was to assess the prevalence of QTc prolongation during ciprofloxacin and fluconazole use. The secondary objective was to determine associated risk factors of QTc prolongation in these patients. METHODS A prospective observational study was performed in patients admitted to the Erasmus University Medical Centre and treated with ciprofloxacin and fluconazole. A 12-lead electrocardiogram (ECG) was recorded at the estimated time to peak concentration (Tmax ) for the last added drug. The main outcome was the proportion of patients with QTc prolongation during treatment. Data on the following potential risk factors were collected: patient characteristics, serum electrolyte levels, dosage of ciprofloxacin and fluconazole, renal and liver function and concomitant use of other QTc-prolonging drugs and cytochrome P450 3A4 inhibitors. RESULTS A total of 170 patients were included, of whom 149 (87.6%) were treated for haematological malignancies. The prevalence of QTc prolongation was 4.7%. No risk factors were found to be associated with QTc prolongation. The QTc interval increased by 10.7 ms [95% confidence interval (CI) 7.2, 14.1 ms] during ciprofloxacin and fluconazole combination therapy. CONCLUSION The prevalence of QTc prolongation in patients using ciprofloxacin and fluconazole is low compared with the prevalence in the general population, which varies from 5% to 11%. In addition, no risk factors were found. Given the low prevalence, routine ECG monitoring in patients on this therapy should be reconsidered.
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The effects of two different doses of ultraviolet-A light exposure on nitric oxide metabolites and cardiorespiratory outcomes.
Monaghan, C, McIlvenna, LC, Liddle, L, Burleigh, M, Weller, RB, Fernandez, BO, Feelisch, M, Muggeridge, DJ, Easton, C
European journal of applied physiology. 2018;(5):1043-1052
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PURPOSE The present study investigated different doses of ultraviolet-A (UV-A) light on plasma nitric oxide metabolites and cardiorespiratory variables. METHODS Ten healthy male participants completed three experimental conditions, 7 days apart. Participants were exposed to no light (CON); 10 J cm2 (15 min) of UV-A light (UVA10) and 20 J cm2 (30 min) of UV-A light (UVA20) in a randomized order. Plasma nitrite [NO2-] and nitrate [NO3-] concentrations, blood pressure (BP), and heart rate (HR) were recorded before, immediately after exposure and 30 min post-exposure. Whole body oxygen utilization ([Formula: see text]), resting metabolic rate (RMR) and skin temperature were recorded continuously. RESULTS None of the measured parameters changed significantly during CON (all P > 0.05). [Formula: see text] and RMR were significantly reduced immediately after UVA10 (P < 0.05) despite no change in plasma [NO2-] (P > 0.05). Immediately after exposure to UVA20, plasma [NO2-] was higher (P = 0.014) and [Formula: see text] and RMR tended to be lower compared to baseline (P = 0.06). There were no differences in [NO2-] or [Formula: see text] at the 30 min time point in any condition. UV-A exposure did not alter systolic BP, diastolic BP or MAP (all P > 0.05). UV-A light did not alter plasma [NO3-] at any time point (all P > 0.05). CONCLUSIONS This study demonstrates that a UV-A dose of 20 J cm2 is necessary to increase plasma [NO2-] although a smaller dose is capable of reducing [Formula: see text] and RMR at rest. Exposure to UV-A did not significantly reduce BP in this cohort of healthy adults. These data suggest that exposure to sunlight has a meaningful acute impact on metabolic function.
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The Effect of Head-to-Head Competition on Behavioural Thermoregulation, Thermophysiological Strain and Performance During Exercise in the Heat.
Corbett, J, White, DK, Barwood, MJ, Wagstaff, CRD, Tipton, MJ, McMorris, T, Costello, JT
Sports medicine (Auckland, N.Z.). 2018;(5):1269-1279
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BACKGROUND It has been suggested that pacing is a thermoregulatory behaviour. We investigated the effect of competition on pacing, performance and thermophysiological strain during exercise in the heat and the psychological factors mediating competition effects. METHOD Eighteen males (maximum oxygen uptake [V O 2max] 3.69 [0.44] L min-1) undertook a preliminary 20-km cool (wet-bulb globe temperature [WBGT] 12 °C) cycling time trial (TT) and three experimental 20-km trials (balanced order): (i) cool TT (CoolSolo); (ii) hot (WBGT 26 °C) TT (HotSolo); (iii) hot head-to-head competition (HotH2H). During TTs, an avatar of the participant's performance was visible. During HotH2H, participants believed they were competing against another participant, but the competitor's avatar replicated their own preliminary (cool) TT. RESULTS TTs (min:sec [SD]) slowed with increased ambient temperature [CoolSolo 35:31 (2:11) versus HotSolo 36:10 (2:26); p = 0.011]. This effect was negated by competition; performances were not different between HotH2H [35:17 (1:52)] and CoolSolo (p = 0.160) and were quicker in HotH2H versus HotSolo (p = 0.001). End-exercise rectal temperature, mean body temperature and physiological strain index were (p < 0.05) higher in HotH2H than either solo condition. Despite faster performance and greater thermophysiological strain, rating of perceived exertion (RPE), thermal comfort and sensation, and perceptual strain index were not different between HotH2H and HotSolo. The difference in end-exercise rectal temperature between HotH2H and HotSolo was related to pre-exercise anticipatory heart rate response (r = 0.608, p = 0.010) and participants' propensity for deliberate risk-taking (B = 0.12, p < 0.001), whereas self-reported resilience predicted change in performance times between HotH2H versus HotSolo (B = - 9.40, p = 0.010). CONCLUSION Competition changes the relationship between perceived and actual thermophysiological state, altering behavioural thermoregulation and increasing thermophysiological strain; this could increase heat-illness risk. Psychophysiological and psychological measures may identify susceptible individuals.
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Blood pressure, heart rate, and mortality in chronic obstructive pulmonary disease: the SUMMIT trial.
Byrd, JB, Newby, DE, Anderson, JA, Calverley, PMA, Celli, BR, Cowans, NJ, Crim, C, Martinez, FJ, Vestbo, J, Yates, J, et al
European heart journal. 2018;(33):3128-3134
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AIMS: To characterize the relationship between blood pressure (BP) or heart rate and mortality and morbidity in chronic obstructive pulmonary disease (COPD). METHODS AND RESULTS We performed post hoc analysis of baseline BP or heart rate and all-cause mortality and cardiovascular events in the SUMMIT trial. SUMMIT was a randomized double-blind outcome trial of 16 485 participants (65 ± 8 years, 75% male, and 47% active smokers) enrolled at 1368 sites in 43 countries. Participants with moderate COPD with or at risk for cardiovascular disease (CVD) were randomized to placebo, long-acting beta agonist, inhaled corticosteroid, or their combination. All-cause mortality increased in relation to high systolic [≥140 mmHg; hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.12-1.45] or diastolic (≥90 mmHg; HR 1.35, 95% CI 1.14-1.59) BP and low systolic (<120 mmHg; HR 1.36, 95% CI 1.13-1.63) or diastolic (<80 mmHg; HR 1.15, 95% CI 1.00-1.32) BP. Higher heart rates (≥80 per minute; HR 1.39, 95% CI 1.21-1.60) and pulse pressures (≥80 mmHg; HR 1.39, 95% CI 1.07-1.80) were more linearly related to increases in all-cause mortality. The risks of cardiovascular events followed similar patterns to all-cause mortality. Similar findings were observed in subgroups of patients without established CVD. CONCLUSION A 'U-shaped' relationship between BP and all-cause mortality and cardiovascular events exists in patients with COPD and heightened cardiovascular risk. A linear relationship exists between heart rate and all-cause mortality and cardiovascular events in this population. These findings extend the prognostic importance of BP to this growing group of patients and raise concerns that both high and low BP may pose health risks.
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Heart Rate Variability Responses of Individuals With and Without Saline-Induced Obstructive Sleep Apnea.
Vena, D, Bradley, TD, Millar, PJ, Floras, JS, Rubianto, J, Gavrilovic, B, Perger, E, Yadollahi, A
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2018;(4):503-510
Abstract
STUDY OBJECTIVES Postoperative development of obstructive sleep apnea (OSA) has been attributed to the fluid overloaded state of patients during the postoperative period. In this context, alterations in cardiac autonomic regulation caused by OSA may explain the increased postoperative risk for adverse cardiovascular events. This study tests the hypothesis that individuals with fluid overload-induced OSA will experience autonomic dysregulation, compared to those without fluid overload-induced OSA. METHODS Twenty-one normotensive, nonobese (mean body mass index 24.5 kg/m2) males (mean age 37 years) underwent a sleep study. Participants were randomly assigned to infusion with saline during sleep either at the minimum rate (control) or as a bolus of 22 mL/kg body weight (intervention). Participants were blinded to the intervention and crossed over to the other study arm after 1 week. Measures of heart rate variability were calculated from electrocardiography recordings presaline and postsaline infusion in the intervention arm. Heart rate variability measures computed were: standard deviation of the RR interval; root mean square of successive differences; low-frequency, high-frequency, and total power; and the ratio of low-frequency to high-frequency power. RESULTS Although presaline infusion values were similar, postsaline infusion values of the standard deviation of the RR interval and high-frequency power were lower in the group whose apnea-hypopnea index increased in response to saline infusion, compared to the group whose apnea-hypopnea index did not increase in response to saline infusion (P < .05 for both). CONCLUSIONS Fluid overload-induced OSA is accompanied by a reduction in heart rate variability, consistent with vagal withdrawal. Future work should explore autonomic dysregulation in the postoperative period and its association with adverse events.
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Heart rate variability and occupational stress-systematic review.
Järvelin-Pasanen, S, Sinikallio, S, Tarvainen, MP
Industrial health. 2018;(6):500-511
Abstract
The aim of this systematic review was to explore studies regarding association between occupational stress and heart rate variability (HRV) during work. We searched PubMed, Web of Science, Scopus, Cinahl and PsycINFO for peer-reviewed articles published in English between January 2005 and September 2017. A total of 10 articles met the inclusion criteria. The included articles were analyzed in terms of study design, study population, assessment of occupational stress and HRV, and the study limitations. Among the studies there were cross-sectional (n=9) studies and one longitudinal study design. Sample size varied from 19 to 653 participants and both females and males were included. The most common assessment methods of occupational stress were the Job Content Questionnaire (JCQ) and the Effort-Reward Imbalance (ERI) questionnaire. HRV was assessed using 24 h or longer Holter ECG or HR monitoring and analyzed mostly using standard time-domain and frequency-domain parameters. The main finding was that heightened occupational stress was found associated with lowered HRV, specifically with reduced parasympathetic activation. Reduced parasympathetic activation was seen as decreases in RMSSD and HF power, and increase in LF/HF ratio. The assessment and analysis methods of occupational stress and HRV were diverse.
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Effect of Na+-channel blockade on the three-dimensional substrate of atrial fibrillation in a model of endo-epicardial dissociation and transmural conduction.
Gharaviri, A, Verheule, S, Eckstein, J, Potse, M, Krause, R, Auricchio, A, Kuijpers, NHL, Schotten, U
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. 2018;(suppl_3):iii69-iii76
Abstract
AIMS: Atrial fibrillation (AF) is a progressive arrhythmia characterized by structural alterations that increase its stability. Both clinical and experimental studies showed a concomitant loss of antiarrhythmic drug efficacy in later stages of AF. The mechanisms underlying this loss of efficacy are not well understood. We hypothesized that structural remodelling may explain this reduced efficacy by making the substrate more three-dimensional. To investigate this, we simulated the effect of sodium (Na+)-channel block on AF in a model of progressive transmural uncoupling. METHODS AND RESULTS In a computer model consisting of two cross-connected atrial layers, with realistic atrial membrane behaviour, structural remodelling was simulated by reducing the number of connections between the layers. 100% of endo-epicardial connectivity represented a healthy atrium. At various degrees of structural remodelling, we assessed the effect of 60% sodium channel block on AF stability, endo-epicardial electrical activity dissociation (EED), and fibrillatory conduction pattern complexity quantified by number of waves, phase singularities (PSs), and transmural conduction ('breakthrough', BT). Sodium channel block terminated AF in non-remodelled but not in remodelled atria. The temporal excitable gap (EG) and AF cycle length increased at all degrees of remodelling when compared with control. Despite an increase of EED and EG, sodium channel block decreased the incidence of BT because of transmural conduction block. Sodium channel block decreased the number of waves and PSs in normal atrium but not in structurally remodelled atrium. CONCLUSION This simple atrial model explains the loss of efficacy of sodium channel blockers in terminating AF in the presence of severe structural remodelling as has been observed experimentally and clinically. Atrial fibrillation termination in atria with moderate structural remodelling in the presence of sodium channel block is caused by reduction of AF complexity. With more severe structural remodelling, sodium channel block fails to promote synchronization of the two layers of the model.
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Effects of a Short-Term Recreational Team Handball-Based Programme on Physical Fitness and Cardiovascular and Metabolic Health of 33-55-Year-Old Men: A Pilot Study.
Póvoas, SCA, Castagna, C, Resende, C, Coelho, EF, Silva, P, Santos, R, Pereira, R, Krustrup, P
BioMed research international. 2018;:4109796
Abstract
Recreational team handball is an intermittent high-intensity exercise mode with physiological demands in the range of those found to enhance health and physical fitness of sedentary adults. We examined the effects of a short-term team handball-based training programme on physical fitness and metabolic and cardiovascular health of sedentary 33-55-year-old former male team handball players. Twenty-four participants were divided into team handball (THG; n=15) and control groups (CG; n=9) and evaluated at baseline and postintervention. During 12 weeks, THG performed 2-3 60-min recreational team handball matches weekly (average: 2.2 ± 0.7), and CG maintained an inactive lifestyle. Average heart rate (HR) during matches was 80 ± 7%HRmax, with peak values of 91 ± 6%HRmax. A time-by-group interaction was shown in aerobic performance (p=0.016), postural balance (p=0.019), maximum oxygen uptake (VO2max) (p=0.023), resting HR (p<0.001), high-density lipoprotein (HDL) cholesterol (p=0.048), and fasting blood glucose (p=0.052) in favor of THG. THG improved aerobic performance (80%, p<0.001), VO2max (14%, p<0.001), and postural balance (27%, p=0.018). Decreases in resting HR (16%, p<0.001) and fasting blood glucose (7%, p=0.015) and increases in HDL cholesterol (11%, p=0.002) were found in THG. Recreational team handball practice shows positive physical fitness and health-related adaptations, with high attendance, which may contribute to the reduction of the risk of developing lifestyle diseases.