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1.
Grapefruit juice prolongs the QT interval of healthy volunteers and patients with long QT syndrome.
Chorin, E, Hochstadt, A, Granot, Y, Khoury, S, Schwartz, AL, Margolis, G, Barashi, R, Viskin, D, Ghantous, E, Schnapper, M, et al
Heart rhythm. 2019;(8):1141-1148
Abstract
BACKGROUND The list of medications linked to drug-induced long QT syndrome (LQTS) is diverse. It is possible that food products too have QT-prolonging potential. OBJECTIVE We tested the effects of grapefruit juice on the QT interval with the methodology used by the pharmaceutical industry to test new drugs. METHODS This was an open-label, randomized, crossover study with blinded outcome evaluation, a thorough QT study of grapefruit juice performed according to the Guidelines for the Clinical Evaluation of QT/QTc for Non-antiarrhythmic Drugs. Thirty healthy volunteers and 10 patients with congenital LQTS were studied. Healthy volunteers drank 2 L of grapefruit juice (in divided doses), or received 400 mg oral moxifloxacin, in a randomized crossover study. Patients with LQTS were tested with only grapefruit. Repeated baseline, off-drug, and on-drug (grapefruit or moxifloxacin) electrocardiograms were scanned and coded. QT measurements were done with electronic calipers. RESULTS In comparison to off-drug electrocardiograms, grapefruit juice led to significant rate-corrected QT (QTc) prolongation. The absolute net QTc prolongation from grapefruit was 14.0 ms (95% confidence interval 6.2-21.7 ms; P < .001). The QT-prolonging effects of grapefruit in healthy volunteers were comparable with those of moxifloxacin. The QT-prolonging effects of grapefruit juice were greater in female patients and particularly marked in patients with LQTS (net QTc prolongation 21.8 ms; 95% confidence interval 3.4-35.3 ms; P = .034). CONCLUSION Grapefruit juice, at doses tested, prolongs the QT interval. The effect is significant in healthy volunteers, greater in female patients, and more so in patients with LQTS.
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A Quarter of a Century Later: What is Dofetilide's Clinical Role Today?
Wolbrette, DL, Hussain, S, Maraj, I, Naccarelli, GV
Journal of cardiovascular pharmacology and therapeutics. 2019;(1):3-10
Abstract
Dofetilide is a class III antiarrhythmic agent approved by the Food and Drug Administration for the conversion of atrial fibrillation and atrial flutter and maintenance of sinus rhythm in symptomatic patients with persistent arrhythmia. Drug trials showed neutral mortality in post-myocardial infarction patients and those with heart failure. This is a review of postmarket data, including real-world efficacy and safety in a variety of populations. Dofetilide has been used off-label with success in patients with paroxysmal atrial fibrillation and atrial flutter, as well as atrial tachycardia and ventricular tachycardia. The real-world acute conversion rate of atrial fibrillation and atrial flutter is higher than that reported in clinical trials. Dofetilide has an acceptable safety profile when initiated (or reloaded) under hospital monitoring and dosed according to creatinine clearance. Dofetilide is well tolerated and a good choice for patients with acceptable renal function and a normal QT interval, especially if atrioventricular nodal blockade needs to be avoided.
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Effect of different doses of supervised aerobic exercise on heart rate recovery in inactive adults who are overweight or obese: results from E-MECHANIC.
Höchsmann, C, Dorling, JL, Apolzan, JW, Johannsen, NM, Hsia, DS, Church, TS, Martin, CK
European journal of applied physiology. 2019;(9):2095-2103
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Abstract
PURPOSE Heart rate recovery (HRR) after exercise is an independent risk factor for cardiovascular disease and mortality. Regular aerobic exercise can improve HRR, yet little is known regarding the dose necessary to promote increases. The aim was to assess the impact of different doses of vigorous-intensity aerobic exercise on HRR in individuals with overweight/obesity. METHODS Data from 137 sedentary adults with overweight/obesity from E-MECHANIC were analyzed. Participants were randomized to either a moderate-dose exercise group (8 kcal/kg body weight/week; KKW), a high-dose exercise group (20 KKW), or a non-exercise control group. HRR was defined as the difference between peak heart rate (HR) during a graded exercise test and the HR after exactly 1 min of active recovery at 1.5 mph and level grade. RESULTS Change in HRR did not differ significantly by exercise group; therefore, the data from both exercise groups were combined. The combined exercise group showed an improvement in HRR of 2.7 bpm (95% CI 0.1, 5.4; p = 0.04) compared to the control group. Those participants who lost more weight during the intervention (non-compensators) increased HRR by 6.2 bpm (95% CI 2.8, 9.5; p < 0.01) compared to those who lost less weight (compensators). Multiple linear regression models indicated that improvements in HRR are independently associated with increases in VO2peak (β = 0.4; 95% CI 0.1, 0.7; p = 0.04) but also influenced by concomitant weight loss (β = 0.6; 95% CI 0.2, 1.1; p = 0.01). CONCLUSION Exercise-induced improvements in 1-min HRR are likely due to increases in cardiorespiratory fitness as well as concomitant weight loss.
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Cardiovascular Effects of Treatment With the Ketone Body 3-Hydroxybutyrate in Chronic Heart Failure Patients.
Nielsen, R, Møller, N, Gormsen, LC, Tolbod, LP, Hansson, NH, Sorensen, J, Harms, HJ, Frøkiær, J, Eiskjaer, H, Jespersen, NR, et al
Circulation. 2019;(18):2129-2141
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Abstract
BACKGROUND Myocardial utilization of 3-hydroxybutyrate (3-OHB) is increased in patients with heart failure and reduced ejection fraction (HFrEF). However, the cardiovascular effects of increased circulating plasma-3-OHB levels in these patients are unknown. Consequently, the authors' aim was to modulate circulating 3-OHB levels in HFrEF patients and evaluate: (1) changes in cardiac output (CO); (2) a potential dose-response relationship between 3-OHB levels and CO; (3) the impact on myocardial external energy efficiency (MEE) and oxygen consumption (MVO2); and (4) whether the cardiovascular response differed between HFrEF patients and age-matched volunteers. METHODS Study 1: 16 chronic HFrEF patients (left ventricular ejection fraction: 37±3%) were randomized in a crossover design to 3-hour of 3-OHB or placebo infusion. Patients were monitored invasively with a Swan-Ganz catheter and with echocardiography. Study 2: In a dose-response study, 8 HFrEF patients were examined at increasing 3-OHB infusion rates. Study 3 to 4: 10 HFrEF patients and 10 age-matched volunteers were randomized in a crossover design to 3-hour 3-OHB or placebo infusion. MEE and MVO2 were evaluated using 11C-acetate positron emission tomography. RESULTS 3-OHB infusion increased circulating levels of plasma 3-OHB from 0.4±0.3 to 3.3±0.4 mM ( P<0.001). CO rose by 2.0±0.2 L/min ( P<0.001) because of an increase in stroke volume of 20±2 mL ( P<0.001) and heart rate of 7±2 beats per minute (bpm) ( P<0.001). Left ventricular ejection fraction increased 8±1% ( P<0.001) numerically. There was a dose-response relationship with a significant CO increase of 0.3 L/min already at plasma-3-OHB levels of 0.7 mM ( P<0.001). 3-OHB increased MVO2 without altering MEE. The response to 3-OHB infusion in terms of MEE and CO did not differ between HFrEF patents and age-matched volunteers. CONCLUSIONS 3-OHB has beneficial hemodynamic effects in HFrEF patients without impairing MEE. These beneficial effects are detectable in the physiological concentration range of circulating 3-OHB levels. The hemodynamic effects of 3-OHB were observed in both HFrEF patients and age-matched volunteers. 3-OHB may potentially constitute a novel treatment principle in HFrEF patients.
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Cardiac Alternans: Mechanisms and Clinical Utility in Arrhythmia Prevention.
Kulkarni, K, Merchant, FM, Kassab, MB, Sana, F, Moazzami, K, Sayadi, O, Singh, JP, Heist, EK, Armoundas, AA
Journal of the American Heart Association. 2019;(21):e013750
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Effects of Heart Rate Reduction With Either Pyridostigmine or Ivabradine in Patients With Heart Failure: A Randomized, Double-Blind Study.
Villacorta, AS, Villacorta, H, Caldas, JA, Precht, BC, Porto, PB, Rodrigues, LU, Neves, M, Xavier, AR, Kanaan, S, Mesquita, CT, et al
Journal of cardiovascular pharmacology and therapeutics. 2019;(2):139-145
Abstract
BACKGROUND Heart rate (HR) reduction with ivabradine has been proved to reduce hospitalization and death from heart failure (HF). We sought to investigate whether pyridostigmine would effectively reduce HR in patients with chronic HF as compared with ivabradine. METHODS Twenty-one patients with HF who were in sinus rhythm with a resting HR over 70 bpm, despite optimal medical treatment, were included in a randomized, double-blind study comparing pyridostigmine versus ivabradine. The initial dose of ivabradine was 5 mg twice daily to reach a target HR between 50 and 60 bpm and could be titrated to a maximum of 7.5 mg twice daily. Pyridostigmine was used in a fixed dose of 30 mg 3 times daily. RESULTS The baseline HR for ivabradine and pyridostigmine groups was 89.1 (13.5) and 80.1 (7.2) bpm, respectively (P = .083). After 6 months of treatment, HR was significantly reduced to 64.8 (8.3) bpm in the ivabradine group (P = .0014) and 63.6 (5.9) bpm in the pyridostigmine group (P = .0001). The N-terminal pro-B-type natriuretic peptide was reduced in the ivabradine group (median: 1308.4 [interquartile range: 731-1896] vs 755.8 [134.5-1014] pg/mL; P = .027) and in the pyridostigmine group (132.8 [89.9-829] vs 100.7 [38-360] pg/mL; P = .002). Inflammatory markers interleukin-1, interleukin-6, and tumor necrosis factor were reduced in both groups. Exercise capacity was improved in both groups, with increments in volume of oxygen utilization (V˙O2; ivabradine: 13.1 vs 15.6, P = .048; pyridostigmine: 13.3 vs 16.7, P = .032). Heart rate recovery in the first minute postexercise was improved with pyridostigmine (11.8 [3.9] vs 18 [6.5]; P = .046), but not with ivabradine (13.3 [6.9] vs 14.1 [8.2]; P = .70). No differences in either group were observed in the myocardial scintigraphy with 123-iodine-metaiodobenzylguanidine. CONCLUSION Both drugs significantly reduced HR, with improvements in exercise capacity and in neurohormonal and inflammatory profiles.
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Unexpectedly prolonged fasting and its consequences on elderly patients undergoing spinal anesthetics. A prospective observational study1.
Yeniay, O, Tekgul, ZT, Okur, O, Koroglu, N
Acta cirurgica brasileira. 2019;(3):e201900309
Abstract
PURPOSE To measure the preoperative fasting durations with respect to time of the day and its effect on vital parameters and electrocardiogram in elderly patients undergoing surgery under spinal anesthesia. METHODS This study investigated 211 patients older than 60 years undergoing elective surgery under spinal anesthesia. Patients scheduled for surgery in morning hours (AM) and afternoon hours (PM) were compared. Patients fasting hours and repeated measurements of mean arterial pressure (MAP), heart rate (HR), peripheral oxygen saturation (Sp02) and the type and number of ischemic electrocardiogram (ECG) signs were recorded and compared [preoperative, zeroth, 2nd,5th,15th,30th minutes following spinal anesthesia(SA)]. RESULTS Mean fasting durations were 12±2.8 and 9.5±2.1 hours in AM group and 15.5±3.4 12.7±4.4 hours in PM group for foods and liquids respectively. ECG changes were significantly more frequent in PM group and body temperatures were significantly higher in AM group patients. CONCLUSION Our study has shown that fasting times in our population is far longer than recommended and fasting prolonged>15 hours is related to a transiently increased cardiac stress and mild hypothermia.
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Caffeine increases parasympathetic reactivation without altering resting and exercise cardiac parasympathetic modulation: A balanced placebo design.
da Silva Rolim, P, da Costa Matos, RA, Von Koenig Soares, EMK, Molina, GE, da Cruz, CJG
European journal of sport science. 2019;(4):490-498
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Abstract
The sympathicotonic effect of caffeine is strongly evidenced in the literature. However, the effects of caffeine or caffeine expectancy on the cardiac parasympathetic modulation remain obscure. Thus, the aim of this study was to investigate the effects of caffeine consumption and expectancy of caffeine consumption on the cardiac parasympathetic modulation under different stress conditions. Twenty-one physically active men (22.3 ± 2.9 years, 25.2 ± 2.7 kg/m2) consumed ∼3 mg/kg of caffeine received as caffeine, caffeine as placebo, placebo as placebo and placebo as caffeine. Parasympathetic modulation was assessed by heart rate variability (HRV-Poincaré SD1 index) at supine and orthostatic positions, during a submaximal exercise (HRV threshold-HRVT) and during each 60 seconds (s) within 300 s of post-exercise active recovery. A factorial ANOVA for repeated measures (p < 0.05) was used to assess the effect of caffeine, expectancy and resting time after caffeine intake on the HRV. No significant effect of caffeine or expectancy was observed on the SD1 value at supine or standing positions (p = 0.47-0.53; p = 0.57-0.31, respectively), despite an increase in this variable after resting periods in both positions (p < 0.001). During exercise, caffeine and expectancy do not alter the HRVT (p = 0.51-0.39). However, higher SD1 values were observed after caffeine administration from 60 to 300 s post-exercise recovery (p = 0.01-0.05) but not for the effects of expectancy (p = 0.19-0.94). We concluded that low doses of caffeine or expectancy do not alter the resting cardiac parasympathetic modulation or HRVT. However, caffeine, but not expectancy, increases parasympathetic reactivation after a submaximal exercise test in young men.
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Oxygen saturation and heart rate in premature: comparison between cup and finger feeding techniques.
Nunes, JA, Bianchini, EMG, Cunha, MC
CoDAS. 2019;(6):e20180221
Abstract
PURPOSE To evaluate the oxygen saturation, heart rate, length of hospital stay and weight preterm infants or preterm newborns (PTNBs) (in the Neonatal Intensive Care Unit in the diet supply by cup and finger feeding techniques, simultaneously with breastfeeding. METHODS Simultaneous randomized clinical trial. Twenty-five preterm infants admitted to the Neonatal Intensive Care Unit of the Public Hospital from October 2011 to February 2012 were selected. The sample was divided into two groups: Eight preterm infants who received the diet in the cup probe group (CPG) who were born on the same day, and 17 by finger probe group (FPG) who were born on the odd day. In the diet offer, the minimum and maximum values of oxygen saturation (O2 Sat) and heart rate (HR) were recorded: before offering the diet, during and after the offer. RESULTS Regarding the variables O2 Sat and HR, no statistically significant differences were observed between the groups, but in the group vs time factor, the groups showed differences, not continuous in the O2 Sat variable. Regarding weight, a statistically significant gain was observed for both groups, and in CPG the highest weight gain was due to the longer hospitalization time. It was verified that FPG presented shorter hospitalization time. CONCLUSION There were no differences regarding O2 Sat and HR. However, when analyzing the time factor, the groups presented some differences, not continuous, indicating the need for other studies for a better understanding of the effect. The FPG presented shorter hospitalization time and the CPG infants had greater weight gain due to longer hospitalization time.
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Effect of ticagrelor on brain natriuretic peptide, heart rate and myocardial enzymes in patients with coronary atherosclerotic heart disease after stenting.
Jia, D, Qin, B, Wei, X
Pakistan journal of pharmaceutical sciences. 2019;(3 Special):1371-1373
Abstract
The main aim of the current work was to investigate the application of ticagrelor in patients with coronary atherosclerotic heart disease (CAHD) and its effects on brain natriuretic peptide (BNP), heart rate (HR) and myocardial enzymes. Seventy-four postoperative patients who underwent stenting for CAHD were selected as subjects, randomly divided into control group (n=37) and observation group (n=37). The control group was treated with clopidogrel after operation, while the observation group was given ticagrelor treatment. The plasma BNP, HR, myocardial zymogram and adverse cardiac events were compared between the two groups. SPSS18.0 software was used for statistical analysis and the count data was analyzed by χ2 test and the measurement data was detected by t-test The levels of BNP, HR, creatine kinase isoenzyme (CK-MB) and troponin (cTnI) in the observation group were all lower than those in the control group at 3 months after treatment (P<0.05). There was no significant difference in the incidence of myocardial infarction, angina pectoris and arrhythmia between the two groups at 3 months after treatment (P>0.05). The utilization of ticagrelor in patients with postoperative stenting for CAHD improved the BNP, HR and myocardial enzyme level in patients, and also reduced the incidence of adverse cardiac events.