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Troponin I levels in permanent atrial fibrillation-impact of rate control and exercise testing.
Horjen, AW, Ulimoen, SR, Enger, S, Norseth, J, Seljeflot, I, Arnesen, H, Tveit, A
BMC cardiovascular disorders. 2016;:79
Abstract
BACKGROUND High-sensitivity troponin I (hs-TnI) and troponin T (hs-TnT) are moderately correlated and independently related to outcome in atrial fibrillation (AF). Rate controlling therapy has been shown to reduce hs-TnT, however the potential impact on hs-TnI levels, and whether this differs from the effects on hs-TnT, has not been investigated previously. METHODS Sixty patients with stable, permanent AF without heart failure or known ischemic heart disease were included in a randomised crossover study (mean age 71 ± 9 years, 18 women). Diltiazem 360 mg, verapamil 240 mg, metoprolol 100 mg, and carvedilol 25 mg were administered once daily for three weeks, in a randomised sequence. At baseline and on the last day of each treatment period, hs-TnI was measured at rest and after a maximal exercise test and compared to hs-TnT. RESULTS Hs-TnI and hs-TnT correlated moderately at baseline (rs = 0.582, p < 0.001). All drugs reduced both the resting and the peak exercise levels of hs-TnI compared with baseline (p < 0.001 for all). The decline in resting hs-TnI and hs-TnT values relative to baseline levels was similar for all drugs except for verapamil, which reduced hs-TnI more than hs-TnT (p = 0.017). Levels of hs-TnI increased significantly in response to exercise testing at baseline and at all treatment regimens (p < 0.001 for all). The relative exercise-induced increase in hs-TnI was significantly larger compared to hs-TnT at baseline (p < 0.001), on diltiazem (p < 0.001) and on verapamil (p = 0.001). CONCLUSIONS In our population of stable, permanent AF patients, all four rate control drug regimens reduced hs-TnI significantly, both at rest and during exercise. The decline in hs-TnI and hs-TnT levels associated with beta-blocker and calcium channel blocker treatment was similar, except for a larger relative decrease in hs-TnI levels following verapamil treatment. TRIAL REGISTRATION www.clinicaltrials.gov ( NCT00313157 ).
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Rate-control drugs affect variability and irregularity measures of RR intervals in patients with permanent atrial fibrillation.
Corino, VD, Ulimoen, SR, Enger, S, Mainardi, LT, Tveit, A, Platonov, PG
Journal of cardiovascular electrophysiology. 2015;(2):137-41
Abstract
INTRODUCTION Irregularity measures have been suggested as risk indicators in patients with atrial fibrillation (AF); however, it is not known to what extent they are affected by commonly used rate-control drugs. We aimed at evaluating the effect of metoprolol, carvedilol, diltiazem, and verapamil on the variability and irregularity of the ventricular response in patients with permanent AF. METHODS AND RESULTS Sixty patients with permanent AF were part of an investigator-blind cross-over study, comparing 4 rate-control drugs (diltiazem, verapamil, metoprolol, and carvedilol). We analyzed five 20-minute segments per patient: baseline and the 4 drug regimens. On every segment, heart rate (HR) variability and irregularity of RR series were computed. The variability was assessed as standard deviation, pNN20, pNN50, pNN80, and rMSSD. The irregularity was assessed by regularity index, approximate (ApEn), and sample entropy. A significantly lower HR was obtained with all drugs, the HR was lowest using the calcium channel blockers. All drugs increased the variability of ventricular response in respect to baseline (as an example, rMSSD: baseline 171 ± 47 milliseconds, carvedilol 229 ± 58 milliseconds; P < 0.05 vs. baseline, metoprolol 226 ± 66 milliseconds; P < 0.05 vs. baseline, verapamil 228 ± 84; P < 0.05 vs. baseline, diltiazem 256 ± 87 milliseconds; P < 0.05 vs. baseline and all other drugs). Only β-blockers significantly increased the irregularity of the RR series (as an example, ApEn: baseline 1.86 ± 0.13, carvedilol 1.92 ± 0.09; P < 0.05 vs. baseline, metoprolol 1.93 ± 0.08; P < 0.05 vs. baseline, verapamil 1.86 ± 0.22 ns, diltiazem 1.88 ± 0.16 ns). CONCLUSION Modification of AV node conduction by rate-control drugs increase RR variability, while only β-blockers affect irregularity.
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Comparison of four single-drug regimens on ventricular rate and arrhythmia-related symptoms in patients with permanent atrial fibrillation.
Ulimoen, SR, Enger, S, Carlson, J, Platonov, PG, Pripp, AH, Abdelnoor, M, Arnesen, H, Gjesdal, K, Tveit, A
The American journal of cardiology. 2013;(2):225-30
Abstract
Rate control of atrial fibrillation (AF) is a main treatment modality. However, data are scarce on the relative efficacy of calcium channel blockers and β blockers or between drugs within each class. The purpose of the present study was to compare the effect of 4 rate-reducing, once-daily drug regimens on the ventricular heart rate and arrhythmia-related symptoms in patients with permanent AF. We included 60 patients (mean age 71 ± 9 years, 18 women) with permanent AF in an investigator-blind cross-over study. Diltiazem 360 mg/day, verapamil 240 mg/day, metoprolol 100 mg/day, and carvedilol 25 mg/day were administered for 3 weeks in a randomized sequence. The 24-hour heart rate was measured using Holter monitoring, and arrhythmia-related symptoms were assessed using the Symptom Checklist questionnaire before randomization and on the last day of each treatment period. The 24-hour mean heart rate was 96 ± 12 beats/min at baseline (no treatment), 75 ± 10 beats/min with diltiazem, 81 ± 11 beats/min with verapamil, 82 ± 11 beats/min with metoprolol, and 84 ± 11 beats/min with carvedilol. All drugs reduced the heart rate compared to baseline (p <0.001 for all). The 24-hour heart rate was significantly lower with diltiazem than with any other drug tested (p <0.001 for all). Compared to baseline, diltiazem significantly reduced both the frequency (p <0.001) and the severity (p = 0.005) of symptoms. In contrast, verapamil reduced symptom frequency only (p = 0.012). In conclusion, diltiazem 360 mg/day was the most effective drug regimen for reducing the heart rate in patients with permanent AF. Arrhythmia-related symptoms were reduced by treatment with the calcium channel blockers diltiazem and verapamil, but not by the β blockers.
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Metoprolol vs. carvedilol or carvedilol plus N-acetyl cysteine on post-operative atrial fibrillation: a randomized, double-blind, placebo-controlled study.
Ozaydin, M, Icli, A, Yucel, H, Akcay, S, Peker, O, Erdogan, D, Varol, E, Dogan, A, Okutan, H
European heart journal. 2013;(8):597-604
Abstract
AIMS: Carvedilol and N-acetyl cysteine (NAC) have antioxidant and anti-inflammatory properties. Aim was to evaluate the efficacy of metoprolol, carvedilol, and carvedilol plus NAC on the prevention of post-operative atrial fibrillation (POAF). METHODS AND RESULTS Patients undergoing cardiac surgery (n = 311) were randomized to metoprolol, carvedilol, or carvedilol plus NAC. Baseline characteristics were similar. The incidence of POAF was lower in the carvedilol plus NAC group compared with the metoprolol group (P < 0.0001) or the carvedilol group (P = 0.03). There was a borderline significance for lower POAF rates in the carvedilol group compared with the metoprolol group (P = 0.06). Duration of hospitalization was lower in the carvedilol plus NAC group compared to the metoprolol group (P = 0.004). Multivariate independent predictors of POAF included left-atrial diameter, hypertension, bypass duration, pre-randomization and pre-operative heart rates, carvedilol plus NAC group vs. metoprolol group, and carvedilol plus NAC group vs. carvedilol group. CONCLUSION Carvedilol plus NAC decreased POAF incidence and duration of hospitalization compared with metoprolol and decreased POAF incidence compared with carvedilol.
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Comparison of rate versus rhythm control in patients with atrial fibrillation and a pacemaker.
Badheka, AO, Marzouka, GR, Rathod, AD, Patel, NJ, Myerburg, RJ, Mitrani, RD
The American journal of cardiology. 2013;(12):1759-63
Abstract
The effect of rate versus rhythm control in patients with atrial fibrillation who have undergone previous pacemaker (PM) implantation is unknown. We evaluated the mortality in patients with atrial fibrillation and a PM randomized to rate or rhythm control treatment strategies. The Atrial Fibrillation Follow-up Investigation of Rhythm Management data set was stratified by the presence (n = 250) or absence (n = 3,810) of a PM at randomization into the rate or rhythm control arm. Kaplan-Meier curves were used for univariate analysis, and proportional hazards were used for multivariate analysis. The subjects with a PM (n = 250) were older (73 vs 69 years, p <0.01) and had a greater prevalence of coronary artery disease (53% vs 37%, p <0.01) and congestive heart failure (33% vs 23%, p <0.01). All-cause mortality was significantly greater in the PM patients who were randomized to the rhythm control arm (n = 128) than in the patients enrolled in the rate control arm with or without a PM (n = 2,027, p <0.01) and those in the rhythm control arm without a PM (n = 1,905, p <0.01). Multivariate analysis revealed that predictors of all-cause mortality included PM patients randomized to the rhythm control arm (hazard ratio 2.59, 95% confidence interval 1.46 to 4.58, p <0.01) and the presence of congestive heart failure (hazard ratio 2.42, 95% confidence interval 1.40 to 4.16, p <0.01). In conclusion, all-cause mortality was greater among patients with atrial fibrillation with a PM, who were randomized to the rhythm control arm of the Atrial Fibrillation Follow-up Investigation of Rhythm Management study compared with all other patients enrolled in the Atrial Fibrillation Follow-up Investigation of Rhythm Management study. The rhythm control strategy in patients with a PM was an independent predictor of mortality.
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Antiarrhythmic use from 1991 to 2007: insights from the Canadian Registry of Atrial Fibrillation (CARAF I and II).
Andrade, JG, Connolly, SJ, Dorian, P, Green, M, Humphries, KH, Klein, GJ, Sheldon, R, Talajic, M, Kerr, CR
Heart rhythm. 2010;(9):1171-7
Abstract
BACKGROUND The pharmacologic management of atrial fibrillation (AF), the most common sustained cardiac arrhythmia, has been traditionally dichotomized into control of ventricular rate or re-establishment and maintenance of sinus rhythm. OBJECTIVE The purpose of this study was to evaluate the use of rate-controlling drugs and antiarrhythmic drugs (AAD) in the Canadian Registry of Atrial Fibrillation (CARAF) over a 16-year period from 1991 through 2007. METHODS 1,400 patients with new-onset paroxysmal AF who were enrolled in CARAF were included in this analysis. We assessed trends in ventricular rate-controlling medication use (digoxin, beta-blockers, and calcium channel blockers) and AAD (class IA, IC, and III antiarrhythmic agents) at baseline and follow-up visits as well as by calendar year. RESULTS AAD use increased initially from 1991 to 1994 (peak use 42.5%) before steadily declining. Sotalol use decreased (27% to 6%), whereas amiodarone use increased (1.6% to 17.9%). Rate-controlling medication use decreased from 1991 to 1995 (54.1% to 34.1%) due to declining digoxin use (62.9% to 16.3%). After 1999, there was a continued increase in rate-controlling medication use (peak use 52.5% in 2007) due to increased beta-blocker use (17% to 45.7%). Calcium channel blockers use changed little over the duration of the study. CONCLUSION The management of AF has undergone significant shifts since 1990, reflecting the influence of drug development, prevailing belief systems, the impact of large clinical trials, and evidence-based recommendations. Monitoring of pharmacotherapy trends will provide insight into the real-world application of evidence-based guidelines as well as allow the opportunity to identify deficiencies and improve patient care.
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Lenient versus strict rate control in patients with atrial fibrillation.
Van Gelder, IC, Groenveld, HF, Crijns, HJ, Tuininga, YS, Tijssen, JG, Alings, AM, Hillege, HL, Bergsma-Kadijk, JA, Cornel, JH, Kamp, O, et al
The New England journal of medicine. 2010;(15):1363-73
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Abstract
BACKGROUND Rate control is often the therapy of choice for atrial fibrillation. Guidelines recommend strict rate control, but this is not based on clinical evidence. We hypothesized that lenient rate control is not inferior to strict rate control for preventing cardiovascular morbidity and mortality in patients with permanent atrial fibrillation. METHODS We randomly assigned 614 patients with permanent atrial fibrillation to undergo a lenient rate-control strategy (resting heart rate <110 beats per minute) or a strict rate-control strategy (resting heart rate <80 beats per minute and heart rate during moderate exercise <110 beats per minute). The primary outcome was a composite of death from cardiovascular causes, hospitalization for heart failure, and stroke, systemic embolism, bleeding, and life-threatening arrhythmic events. The duration of follow-up was at least 2 years, with a maximum of 3 years. RESULTS The estimated cumulative incidence of the primary outcome at 3 years was 12.9% in the lenient-control group and 14.9% in the strict-control group, with an absolute difference with respect to the lenient-control group of -2.0 percentage points (90% confidence interval, -7.6 to 3.5; P<0.001 for the prespecified noninferiority margin). The frequencies of the components of the primary outcome were similar in the two groups. More patients in the lenient-control group met the heart-rate target or targets (304 [97.7%], vs. 203 [67.0%] in the strict-control group; P<0.001) with fewer total visits (75 [median, 0], vs. 684 [median, 2]; P<0.001). The frequencies of symptoms and adverse events were similar in the two groups. CONCLUSIONS In patients with permanent atrial fibrillation, lenient rate control is as effective as strict rate control and is easier to achieve. (ClinicalTrials.gov number, NCT00392613.)
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Slow infusion of calcium channel blockers compared with intravenous adenosine in the emergency treatment of supraventricular tachycardia.
Lim, SH, Anantharaman, V, Teo, WS, Chan, YH
Resuscitation. 2009;(5):523-8
Abstract
INTRODUCTION The emergency treatment of supraventricular tachycardia (SVT) has, over the last two decades, changed from verapamil to adenosine primarily owing to documented hypotensive episodes occurring with rapid bolus infusions of the calcium channel blocker. Slow infusions of calcium channel blockers have not previously demonstrated hypotension to any significant degree. The aim of this study was to compare the efficacy and safety of bolus intravenous adenosine and slow infusion of the calcium channel blockers verapamil and diltiazem in the emergency treatment of spontaneous SVT. METHODS A prospective randomized controlled trial with one group receiving bolus intravenous adenosine 6 mg followed, if conversion was not achieved, by adenosine 12 mg; and the other group receiving a slow infusion of either verapamil at a rate of 1mg per minute up to a maximum dose of 20mg, or diltiazem at a rate of 2.5mg per minute up to a maximum dose of 50mg. These infusions would be stopped at time of conversion of the SVT or when the whole dose was administered. Heart rate and blood pressure was continuously monitored during drug infusion and for up to 2h post-conversion. RESULTS A total of 206 patients with spontaneous SVT were analysed. Of these, 102 were administered calcium channel blockers (verapamil=48, diltiazem=54) and 104 were given adenosine. The conversion rates for the calcium channel blockers (98%) were statistically higher than the adenosine group (86.5%), p=0.002, RR 1.13, 95% CI 1.04-1.23. The initial mean change in blood pressure post-conversion in the calcium channel blocker group was -13.0/-8.1 mmHg (verapamil) and -7.0/-9.4 mmHg (diltiazem) and 2.6/-1.7 mmHg for adenosine. Only one patient in the calcium channel group (0.98%) (95% CI 0.025-5.3) developed hypotension, and none in the adenosine group. CONCLUSION Slow infusion of calcium channel blockers is an alternative to adenosine in the emergency treatment of stable patients with SVT. Calcium channel blockers are safe and affordable for healthcare systems where the availability of adenosine is limited.
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Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 2: are calcium channel blockers superior to digoxin for controlling the ventricular rate in patients with acute atrial fibrillation?
Parris, RJ, Clarke, SF
Emergency medicine journal : EMJ. 2009;(12):881-3
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Effect of intra-coronary nicorandil administration prior to reperfusion in acute ST segment elevation myocardial infarction.
Lee, HC, An, SG, Choi, JH, Lee, TK, Kim, J, Kim, JH, Chun, KJ, Hong, TJ, Shin, YW, Lee, SK
Circulation journal : official journal of the Japanese Circulation Society. 2008;(9):1425-9
Abstract
BACKGROUND Intravenous nicorandil infusion with percutaneous coronary intervention (PCI) has been reported to reduce reperfusion injury events and improve cardiac function in patients with acute myocardial infarction (MI). However, there is limited information on the use of intracoronary nicorandil. METHODS AND RESULTS In the present study, 73 patients with acute ST segment elevation MI undergoing PCI were randomly assigned to the Nicorandil Group (n=37) or the Control Group (n=36). The composite endpoints were the incidences of ventricular arrhythmia, no-reflow and slow flow. A significant difference in the composite endpoint was observed in the Nicorandil Group when compared with the Control Group (p=0.037). The occurrence of post Thrombolysis In Myocardial Infarction (TIMI) grade 3 was significantly higher in the Nicorandil Group (p=0.019). Major adverse cardiac events during hospitalization and within 30 days of treatment were similar between the 2 groups. CONCLUSION Administration of intracoronary nicorandil reduced the occurrence of no-reflow, slow reflow, and reperfusion arrhythmia, and improved the myocardial perfusion grade, TIMI flow during PCI and improved clinical outcomes in patients with acute MI.