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Despite the high prevalence of atrial fibrillation (AF), there is a lack of recommendations for physical activity and exercise in individuals with AF, including athletes with AF. With the aim to review studies that have investigated effects and safety of exercise in individuals with AF, we conducted a literature search in Pubmed using the key words atrial fibrillation AND exercise OR physical activity OR exercise/adverse effects OR adverse outcome. Observational data from one registry suggest that regular exercise is associated with reduced mortality in AF patients. Three randomized controlled trials (RCTs) have demonstrated that 12-week exercise interventions might reduce the burden of AF and improve exercise capacity by 10–16% in patients with paroxysmal or persistent AF. Three small RCTs suggest that exercise might improve exercise capacity with 15–41% in patients with permanent AF. Exercise might improve quality of life in patients with AF. Data on safety of exercise are sparse. No studies have evaluated the effect of exercise in athletes with AF. Despite weak evidence, we suggest that individuals with AF should exercise regularly after evaluation of underlying conditions. Recommendations should be individualized. There is a lack of data to support exercise recommendations in athletes with AF.

As cardiac troponins emerge as prognostic markers in atrial fibrillation (AF), it is important to identify mechanisms initiating and perpetuating cardiac troponin release, including its relations to other circulating biomarkers, in AF populations. We studied associations between high-sensitivity troponin I (hs-TnI) and markers representing myocardial wall tension, inflammation and haemostasis in persistent AF.In a double blind, placebo-controlled study, 171 patients referred for electrical cardioversion for persistent AF were randomised to receive candesartan or placebo for 3-6 weeks before and 6 months after cardioversion. Associations between baseline levels of hs-TnI and other biomarkers were investigated by bivariate non-parametric correlations (Spearman's correlation coefficient denoted rBaseline levels of hs-TnI correlated significantly, although weakly, with interleukin-6 (rHs-TnI correlated weakly with biomarkers representing myocardial wall tension, inflammation and haemostasis in persistent AF. The lack of any strong correlation between hs-TnI and the investigated biomarkers is in concert with the idea that hs-TnI release is an independent process parallel to other pathophysiological mechanisms associated with AF.

Objectives: We hypothesised that high-sensitivity troponin I (hs-TnI) might predict long-term rhythm outcome after cardioversion for persistent atrial fibrillation (AF), and that maintenance of sinus rhythm and/or treatment with the angiotensin II type 1 receptor blocker candesartan would reduce hs-TnI levels. Methods: In a double-blind, placebo-controlled study, 171 patients referred for electrical cardioversion for AF were randomised to receive candesartan or placebo for 3-6 weeks before cardioversion and for 6 months after electrical cardioversion. Blood samples for analysis of hs-TnI (Abbott Diagnostics) were available in 129 patients at baseline and in 60 successfully cardioverted patients at study end. Results: Hs-TnI was detectable in all subjects, with a median value of 5.3 ng/l (25th percentile 3.7, 75th percentile 7.2). hs-TnI at baseline was not predictive of rhythm outcome 6 months after electrical cardioversion for persistent AF. Treatment with candesartan did not influence the levels of hs-TnI. hs-TnI was unchanged from baseline to study end in patients who maintained sinus rhythm [4.9 (3.7, 7.0) and 5.0 (4.0, 6.4) ng/l, respectively; p = 0.699). Conclusions: hs-TnI did not predict AF recurrence after cardioversion. hs-TnI levels were unchanged in patients maintaining sinus rhythm for 6 months after electrical cardioversion. hs-TnI levels were not influenced by treatment with candesartan.

The aim of the present study was to evaluate diurnal variations of the variability and irregularity of heart rate (HR) in patients with permanent atrial fibrillation (AF) with and without rate control drugs. Thirty-eight patients with permanent AF were part of an investigator-blind crossover study comparing diltiazem, verapamil, metoprolol, and carvedilol. We analyzed five Holter recordings per patient: at baseline (no rate control drug) and with each of the four drug regimens. HR, variability (SD; percentages of interval differences of successive RR intervals of >20, 50, and 80 ms; and root of the mean squared differences of successive RR intervals), and irregularity (approximate and sample entropy) parameters were computed in 20-min long nonoverlapping segments. Circadian rhythmicity was evaluated using cosinor analysis to each parameter series, which is characterized by the 24-h mean [midline statistic of rhythm (MESOR)] and excursion over the mean (amplitude). Arrhythmia-related symptoms were assessed by a questionnaire measuring symptom severity and frequency. HR and variability parameters showed a significant circadian variation in most patients, whereas only a small minority of the patients had circadian variations of irregularity parameters. Patients with circadian approximate entropy n at baseline had more severe symptoms (symptom severity: 9 ± 4 vs. 6 ± 5, P < 0.05, circadian vs. noncircadian variations). All drugs decreased the MESOR of HR and increased the MESOR of variability parameters. Only carvedilol and metoprolol decreased the normalized amplitude over 24 h of all parameters and HR. In conclusion, HR and RR variability parameters present a circadian variation in patients with permanent AF, whereas few patients demonstrated circadian fluctuations in irregularity parameters, suggesting different physiological mechanisms.

Aim We aimed at assessing changes in AV nodal properties during administration of the beta blockers metoprolol and carvedilol, and the calcium channel blockers diltiazem and verapamil from electrocardiographic data. Methods Parameters accounting for the functional refractory periods of the slow and fast pathways (aRPs and aRPf) were estimated using atrial fibrillatory rate (AFR) and ventricular response assessed from 15-min ECG segments recorded at baseline and on drug treatment from sixty patients with permanent AF. Results The results showed that AFR and HR were significantly reduced for all drugs, and that aRPs and aRPf were significantly prolonged in both pathways. The prolongation in aRP was significantly larger for the calcium channel blockers than for the beta blockers. Conclusions The changes observed in the AV node parameters are in line with the results of previous electrophysiological studies performed in patients during sinus rhythm, therefore supporting the clinical value of the method.

Atrial fibrillation (AF) has been associated with elevated levels of cardiac troponins; however, it is not clear if this association is independent of underlying cardiovascular disease. The aim of this study was to investigate the impact of AF on cardiac troponin I levels in a 75-year-old cohort from the general population, using a recently introduced, highly sensitive assay.All 75-year-old citizens in Asker and Baerum counties were invited to participate in a prevalence study of AF. High-sensitive troponin I (hs-TnI) levels were measured (Abbott Diagnostics) in serum samples collected from 62 subjects with AF and a gender-matched control group of 126 subjects in sinus rhythm.Hs-TnI was detectable in all subjects (median 7.3 ng/L [range 3.0-88.7]). Patients with AF had higher levels than subjects in sinus rhythm (8.3 ng/L [3.7-88.7] vs. 6.8 ng/L [3.0-77.5]; p = 0.011). Male gender (p = 0.002), hypertension (p = 0.001), coronary heart disease (p0.001), heart failure (p0.001), prior stroke or transient ischemic attack (p = 0.013) and serum creatinine (p0.001) were all associated with higher levels of hs-TnI in univariate analysis. Heart failure and coronary heart disease remained significantly associated with hs-TnI in multivariate analysis, whereas the relation between AF and hs-TnI was no longer statistically significant.All subjects had detectable levels of hs-TnI. AF patients had higher hs-TnI levels than subjects in sinus rhythm; however, this difference was not statistically significant after adjustment for heart failure and coronary heart disease.

Heart Rate Variability and Irregularity During AF IntroductionIrregularity 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 ResultsSixty 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 -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). ConclusionModification of AV node conduction by rate-control drugs increase RR variability, while only -blockers affect irregularity. (Less)

Aims Rate control of atrial fibrillation (AF) has become a main treatment modality, but we need more knowledge regarding the different drugs used for this purpose. In this study, we aimed to compare the effect of four common rate-reducing drugs on exercise capacity and levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with permanent AF. Methods and results We included 60 patients (mean age 71 ± 9 years, 18 women) with permanent AF and normal left ventricular function in a randomized, cross-over, investigator-blind study. Diltiazem 360 mg, verapamil 240 mg, metoprolol 100 mg, and carvedilol 25 mg were administered o.d. for 3 weeks. At baseline and on the last day of each treatment period, the patients underwent a maximal cardiopulmonary exercise test and blood samples were obtained at rest and at peak exercise. The exercise capacity (peak VO2) was significantly lower during treatment with metoprolol and carvedilol compared with baseline (no treatment) or treatment with diltiazem and verapamil ( P < 0.001 for all). Compared with baseline, treatment with diltiazem and verapamil significantly reduced the NT-proBNP levels both at rest and at peak exercise, whereas treatment with metoprolol and carvedilol increased the levels ( P < 0.05 for all). Conclusion Rate-reducing treatment with diltiazem or verapamil preserved exercise capacity and reduced levels of NT-proBNP compared with baseline, whereas treatment with metoprolol or carvedilol reduced the exercise capacity and increased levels of NT-proBNP.

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. 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. Hs-TnI and hs-TnT correlated moderately at baseline (rs = 0.582, p

The objective of this study was to investigate the impact of atrial fibrillation (AF) on serum levels of N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) in a 75-year-old population.All 75-year-old citizens in Asker and Baerum counties in Norway were invited to participate in a prevalence study of AF. Blood samples for measurement of NT-proBNP were collected at rest from 61 subjects with AF and a gender-matched control group of 126 subjects in sinus rhythm. NT-proBNP was measured in serum using the Elecsys proBNP sandwich immunoassay (Roche Diagnostics, Basel, Switzerland).Subjects with permanent AF had higher levels of NT-proBNP (median 1119 pg/mL (interquartile range 701, 1643)) than subjects with paroxysmal AF (257 pg/mL (169, 382)) and controls (95 pg/mL (60, 171)), p0.001 for both.The presence of AF was still significantly associated with higher log NT-proBNP (B=0.61, p0.001) after adjusting for the presence of heart failure, coronary heart disease and hypertension.In this stable, out-of-hospital population of 75-year-old subjects, AF was independently associated with increased levels of NT-proBNP. Permanent AF was associated with higher NT-proBNP levels than paroxysmal AF.

Background Detectable levels of troponins are often found in serum of patients with atrial fibrillation (AF), and recent reports suggest that Tn concentrations are independently related to patient prognosis. Hypothesis We hypothesized that treatment with common rate-reducing drugs might lower the levels of cardiac troponin T (TnT) in patients with permanent AF. We also wanted to investigate whether the different drugs would impact the Tn levels differently. Methods Sixty patients were included (mean age 71 ± 9 years, 18 women) in this randomized crossover study. All patients had stable, permanent AF without ischemic heart disease or congestive heart failure. Diltiazem 360 mg, verapamil 240 mg, metoprolol 100 mg, and carvedilol 25 mg were administered once daily for 3 weeks, in a randomized sequence. At baseline and on the last day of each treatment period, TnT concentrations were measured at rest and after a maximal exercise test. Results TnT was detectable in all patients. In 22% of the patients, TnT concentrations were above the threshold normally used for diagnosing myocardial infarction. All drugs reduced the levels of TnT significantly compared with baseline (P < 0.001 for all), but there were no significant differences between the treatments. Levels of TnT increased significantly in response to exercise testing (P < 0.001 for all). Conclusions Elevated TnT was demonstrated in a large proportion of stable patients with permanent AF without ischemic heart disease. A moderate reduction of heart rate by the study drugs was associated with a significant reduction in levels of TnT.

In this study, we investigated the relation between sample entropy (SampEn) of HRV series and the connected theoretical value (SE TH ), obtained for the autoregressive (AR) models fitted to the same sequences. AR models are commonly used for parametrical spectral analysis and classical HRV spectral parameters were considered as well. The analysis was performed on a subpopulation of the Rate Control in Atrial Fibrillation (RATAF) study, where RR series were collected before and after a β-blocker, Carvedilol, was administered. SampEn, SE TH and the spectral parameters were significantly different after drug administration. However while SampEn is sensible to nonlinearities or non-Gaussianity in the series, the other parameters are not. To investigate further the changes in the series induced by the drug, both synthetic series generated by the fitted AR models and IAAFT surrogates were employed. The results suggest a reduction in non-Gaussianity as long as a relatively smaller increase in regularity.

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 (p0.001 for all). The 24-hour heart rate was significantly lower with diltiazem than with any other drug tested (p0.001 for all). Compared to baseline, diltiazem significantly reduced both the frequency (p0.001) 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.

Background: The importance of endothelial dysfunction in atrial fibrillation (AF) is not clarified. The aim of this study was to evaluate endothelial dysfunction assessed by selected inflammatory and haemostatic endothelial markers and nitric oxide (NO) associated variables as related to the presence of AF in an elderly population. NO is known to express anti-thrombotic as well as vasoactive properties. Methods: This is a cross sectional study of 75-year old subjects with AF (n = 62) and control subjects in sinus rhythm (n = 124), matched for gender. Fasting blood samples were collected for analyses of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO-synthase, L-arginine, E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand factor (vWF). Results: Levels of vWF and ADMA were significantly higher in AF patients vs controls (P = 0.023 and P < 0.001, respectively) and the L-arginine/ADMA ratios were lower (P = 0.015), the latters still significant after adjustment for relevant covariates (P = 0.007 and P = 0.037, respectively). No significant differences in the levels of VCAM-1 and E-selectin were observed between the groups. When dividing the ADMA levels into quartiles there was a significant trend for having AF with increasing levels of ADMA (P < 0.001) with a cut-off at the 25th percentile (< 0.54 µmol/L), giving an adjusted OR for having AF of 12.46 (95% CI 3.11 - 49.86) (P < 0.001) with higher levels. A similar inverse trend was seen for the L-arginine/ADMA ratio. Conclusion: Our population of 75-year-old AF patients had significantly impaired endothelial function assessed by increased levels of vWF, and more pronounced by high levels of ADMA. The results indicate AF in the elderly to be closely associated with the regulatory pathway of NO. Cardiol Res. 2012;3(3):109-115 doi: https://doi.org/10.4021/cr175w

Aims: The aim of this study was to compare the effects of four common rate-reducing drugs on levels of cardiac troponin T (cTnT) at rest and after exercise in patients with permanent atrial fibrillation (AF). Methods: We included 60 patients (mean age 71±9 years, 18 women) with permanent AF without ischemic heart disease or congestive heart failure in a cross-over, investigator-blind study. Diltiazem 360 mg, verapamil 240 mg, metoprolol 100 mg and carvedilol 25 mg were administered o.d. for three weeks, in a randomized sequence. At baseline and on the last day of each treatment period, the patients underwent a maximal cardiopulmonary exercise test with blood sampling for high-sensitivity cTnT analyses at rest, at peak exercise and 15 minutes after peak exercise. Results: Levels of cTnT were detectable in all patients. In 22% of the patients the levels of cTnT were above the threshold for diagnosing myocardial infarction. All treatments reduced the levels of cTnT significantly compared to baseline (p