Association of atrial arrhythmias with thrombospondin-1 in patients with acute myocardial infarction.

OBJECTIVES: Atrial remodeling is the main developmental cause of atrial arrhythmias (AA), which may induce atrial fibrillation, atrial flutter, atrial tachycardia, and frequent premature atrial beats in acute myocardial infarction (AMI) patients. Thrombospondin-1 (TSP-1) has been shown to play an important role in inflammatory and fibrotic processes, but its role in atrial arrhythmias is not well described. The purpose of this study was to investigate the role of TSP-1 in AMI patients with atrial arrhythmias. METHODS: A total of 219 patients with AMI who underwent percutaneous coronary intervention and with no previous arrhythmias were included. TSP-1 were analyzed in plasma samples. Patients were classified into 2 groups, namely, with and without AA during the acute phase of MI. Continuous electrocardiographic monitoring was used for AA diagnosis in hospital. RESULTS: Twenty-four patients developed AA. Patients with AA had higher TSP-1 levels (29.01 ± 25.87 µg/mL vs 18.36 ± 10.89 µg/mL, p < 0.001) than those without AA. AA patients also tended to be elderly (65.25 ± 9.98 years vs 57.47 ± 10.78 years, p < 0.001), had higher Hs-CRP (39.74 ± 43.50 mg/L vs 12.22 ± 19.25 mg/L, p < 0.001) and worse heart function. TSP-1 (OR 1.033; 95% CI 1.003-1.065, p = 0.034), Hs-CRP (OR 1.023; 95% CI 1.006-1.041, p = 0.008), age (OR 1.067; 95% CI 1.004-1.135, p = 0.038) and LVDd (OR 1.142; 95% CI 1.018-1.282, p = 0.024) emerged as independent risk factors for AA in AMI patients. CONCLUSION: TSP-1 is a potential novel indicator of atrial arrhythmias during AMI.

Prospective Evaluation of Clinico-Pathological Predictors of Postoperative Atrial Fibrillation: An Ancillary Study From the OPERA Trial.

BACKGROUND: Postoperative atrial fibrillation (POAF) occurs in 30% to 50% of patients undergoing cardiac surgery and is associated with increased morbidity and mortality. Prospective identification of structural/molecular changes in atrial myocardium that correlate with myocardial injury and precede and predict risk of POAF may identify new molecular pathways and targets for prevention of this common morbid complication. METHODS: Right atrial appendage samples were prospectively collected during cardiac surgery from 239 patients enrolled in the OPERA trial (Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation), fixed in 10% buffered formalin, and embedded in paraffin for histology. We assessed general tissue morphology, cardiomyocyte diameters, myocytolysis (perinuclear myofibril loss), accumulation of perinuclear glycogen, interstitial fibrosis, and myocardial gap junction distribution. We also assayed NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-cTnT, CRP (C-reactive protein), and circulating oxidative stress biomarkers (F2-isoprostanes, F3-isoprostanes, isofurans) in plasma collected before, during, and 48 hours after surgery. POAF was defined as occurrence of postcardiac surgery atrial fibrillation or flutter of at least 30 seconds duration confirmed by rhythm strip or 12-lead ECG. The follow-up period for all arrhythmias was from surgery until hospital discharge or postoperative day 10. RESULTS: Thirty-five percent of patients experienced POAF. Compared with the non-POAF group, they were slightly older and more likely to have chronic obstructive pulmonary disease or heart failure. They also had a higher European System for Cardiac Operative Risk Evaluation and more often underwent valve surgery. No differences in left atrial size were observed between patients with POAF and patients without POAF. The extent of atrial interstitial fibrosis, cardiomyocyte myocytolysis, cardiomyocyte diameter, glycogen score or Cx43 distribution at the time of surgery was not significantly associated with incidence of POAF. None of these histopathologic abnormalities were correlated with levels of NT-proBNP, hs-cTnT, CRP, or oxidative stress biomarkers. CONCLUSIONS: In sinus rhythm patients undergoing cardiac surgery, histopathologic changes in the right atrial appendage do not predict POAF. They also do not correlate with biomarkers of cardiac function, inflammation, and oxidative stress. Graphic Abstract: A graphic abstract is available for this article.

Exploration of pathophysiological pathways for incident atrial fibrillation using a multiplex proteomic chip.

Objective: Atrial fibrillation (AF) is the most common arrhythmia and associated with increased morbidity and mortality. Its increasing prevalence calls for novel biomarkers to identify underlying pathophysiological mechanisms as well as patients at risk. Methods: Plasma samples from 1694 individuals from the Swedish population-based Malmö Preventive Project (mean age 69.5 years; 29.3% female; mean follow-up time 9.7±3.1 years) were analysed with the Olink proximity extension assay CVD III panel consisting of 92 proteins to identify proteins associated with incident AF or atrial flutter, referred to as incident AF. Incident cases of AF (n=278) were retrieved by linkage to the registers. Participants were followed until the first episode of AF or until censoring by death or emigration. Bonferroni-corrected multivariable Cox regression models adjusted for known risk factors were used to explore possible associations of the 92 proteins and incidence of AF. Results: Multivariable Cox regression analyses of 11 proteins associated with incident AF (mean follow-up time 9.7±3.1 years) after Bonferroni correction confirmed N-terminal pro-B-type natriuretic peptide (HR per 1 SD increment (95% CI) 1.80 (1.58 to 2.04); p=1.2×10-19) as risk marker of incident AF. Further, matrix metalloproteinase-2 (1.22 (1.07 to 1.39); p=0.002) and osteopontin (1.27 (1.12 to 1.44); p=2.7×10-4) were associated with incident AF at follow-up independently of traditional risk markers and NT-proBNP. Conclusion: In a general Swedish population, we confirmed the well-known association of NT-proBNP with incident AF and also identified matrix metalloproteinase-2 and osteopontin as novel risk markers for incident AF, independently of traditional risk factors and NT-proBNP.

Potassium infusion increases the likelihood of conversion of recent-onset atrial fibrillation-A single-blinded, randomized clinical trial.

BACKGROUND: The optimal antiarrhythmic management of recent-onset atrial fibrillation (ROAF) or atrial flutter is controversial and there is a considerable variability in clinical treatment strategies. It is not known if potassium infusion has the potential to convert ROAF or atrial flutter to sinus rhythm (SR). Therefore, we aimed to investigate if patients with ROAF or atrial flutter and plasma-potassium levels ≤4.0 mmol/L have increased probability to convert to SR if the plasma-potassium level is increased towards the upper reference range (4.1-5.0 mmol/L). METHODS: In a placebo-controlled, single-blinded trial, patients with ROAF or atrial flutter and plasma-potassium ≤4.0 mmol/L presenting between April 2013 and November 2017 were randomized to receive potassium chloride (KCl) infusion (n = 60) or placebo (n = 53). Patients in the KCl group received infusions at one of three different rates: 9.4 mmol/h (n = 11), 12 mmol/h (n = 19), or 15 mmol/h (n = 30). RESULTS: There was no statistical difference in the number of conversions to SR between the KCl group and placebo [logrank test, P = .29; hazard ratio (HR) 1.20 (CI 0.72-1.98)]. However, KCl-infused patients who achieved an above-median hourly increase in plasma-potassium (>0.047 mmol/h) exhibited a significantly higher conversion rate compared with placebo [logrank P = .002; HR 2.40 (CI 1.36-4.21)] and KCl patients with below-median change in plasma-potassium [logrank P < .001; HR 4.41 (CI 2.07-9.40)]. Due to pain at the infusion site, the infusion was prematurely terminated in 10 patients (17%). CONCLUSIONS: Although increasing plasma-potassium levels did not significantly augment conversion of ROAF or atrial flutter to SR in patients with potassium levels in the lower-normal range, our results indicate that this treatment may be effective when a rapid increase in potassium concentration is tolerated and achieved.

Association between serum potassium levels and short-term mortality in patients with atrial fibrillation or flutter co-treated with diuretics and rate- or rhythm-controlling drugs.

AIMS: We investigated the association between potassium levels and 90-day all-cause mortality in atrial fibrillation or flutter (AF) patients co-treated with diuretics and rate- or rhythm-controlling drugs. METHODS AND RESULTS: During 2000-12, first-time AF patients treated with beta-blockers, amiodarone, sotalol, verapamil, or digoxin combined with any diuretic within 90 days post-AF discharge were included. Following co-treatment, a potassium measurement within 90 days after initiating diuretic treatment was required. Mortality risk associated with potassium <3.5, 3.5-3.7, 3.8-4.0, 4.5-4.7, 4.8-5.0, and >5.0 mmol/L (reference: 4.1-4.4 mmol/L) was assessed using multivariable Cox regression. In total, 14 425 AF patients were included (median age: 78 years; women: 52%). Patients most often received beta-blocker monotherapy (29%), beta-blockers and digoxin combined (25%), digoxin monotherapy (24%), amiodarone monotherapy (3%), and verapamil monotherapy (3%). Increased 90-day mortality risk was associated with <3.5 mmol/L [hazard ratio (HR) 2.05, 95% confidence interval (CI) 1.68-2.50], 3.5-3.7 mmol/L (HR 1.28, 95% CI 1.05-1.57), 4.5-4.7 mmol/L (HR 1.20, 95% CI 1.02-1.41), 4.8-5.0 mmol/L (HR 1.37, 95% CI 1.14-1.66), and >5.0 mmol/L: (HR 1.84, 95% CI 1.53-2.21). Compared with beta-blocker monotherapy, rate- or rhythm-controlling drugs did not modify the association between potassium groups and mortality risk. CONCLUSION: In addition to hypo- and hyperkalaemia, low and high normal range potassium levels were associated with increased 90-day mortality risk in AF patients co-treated with diuretics and rate- or rhythm-controlling drugs. These associations were independent of rate- or rhythm-controlling drugs.

Evaluation of myocardial injury induced by different ablation approaches (radiofrequency ablation versus cryoablation) in atrial flutter patients: a meta-analysis.

Background: To evaluate myocardial injury in Atrial flutter (AFL) patients undergoing Radiofrequency ablation (RF) and cryoablation (CRYO) treatments.Methods: We conducted a systematic search on PubMed, Embase, Cochrane Library, and CBM databases. All relevant clinical trials (up to October 2018) on myocardial injury in AFL patients were retrieved and subsequent results analyzed with a random-effects model or a fixed-effects model.Results: A total of eight clinical trials with a sample size of 644 patients, were identified and incorporated in the present study. The results indicated no significant differences in creatine kinase (CK) levels (mean difference (MD) = 62.74, P=0.46; 4-6 h and MD = 30.73, P=0.49; 12-24 h after ablation), creatine kinase MB(CK-MB) levels (MD = 17.32, P=0.25; 12-24 h post-ablation), troponinI (TnI) levels (MD = 0.12, P=0.08; 6 h after ablation), and troponin T (TnT) levels (MD = 0.30, P=0.08; 4-6 h post-ablation) between the two treatment approaches. However, patients receiving CRYO xhibited higher levels of CK (MD = 179.54, P=0.04; tested immediately after the procedure), CK-MB (MD = 10.08, P=0.004) 4-6 h after ablation, and TnT (MD = 0.19, P=0.002) tested the next morning. Moreover, those patients had a significantly reduced pain perception (odds ratio (OR) = 0.05, P=0.04) compared with those in the RF group.Conclusion: These results indicate that CRYO in comparison with RF significantly increases myocardial injury in AFL patients. Additionally, it decreases pain perception during the procedure. Further large-sampled studies are needed to support these findings.

Collagen Biomarkers and Incidence of New Onset of Atrial Fibrillation in Subjects With No Overt Cardiovascular Disease at Baseline: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Atrial fibrosis is a hallmark of structural remodeling in atrial fibrillation (AF). Plasma procollagen type III N-terminal propeptide (PIIINP) reflects collagen synthesis and degradation while collagen type I carboxy-terminal telopeptide (ICTP) reflects collagen degradation. We aimed to study baseline plasma PIIINP and ICTP and their associations with incident AF in participants initially free of overt cardiovascular disease. METHODS: In a stratified sample of the Multi-Ethnic Study of Atherosclerosis, initially aged 45-84 years, 3071 participants had both PIIINP and ICTP measured at baseline. Incident AF in 10-year follow-up was based on a hospital International Classification of Diseases code for AF or atrial flutter, in- or outpatient Medicare claims through 2011 (primarily in those aged 65-84 years), or ECG 10 years after baseline (n=357). The associations of PIIINP and ICTP with incident AF were estimated using Poisson regression with follow-up time offset. RESULTS: Baseline PIIINP (5.50±1.55 µg/L) and ICTP (mean±SD, 3.41±1.37 µg/L) were positively related (both P<0.0001) to incident AF in a model adjusting for age, race/ethnicity, and sex, with an apparent threshold (relative incidence density 2.81 [1.94-4.08] for PIIINP ≥8.5 µg/L [3.5% of the sample] and 3.46 [2.36-5.07] for ICTP ≥7 µg/L [1.7% of the sample]). Findings were attenuated but remained statistically significant after further adjustment for systolic blood pressure, height, body mass index, smoking, and renal function. Additional adjustment for other risk factors and biomarkers of inflammation did not alter conclusions. CONCLUSIONS: Plasma collagen biomarkers, particularly at elevated levels, were associated with excess risk for AF.

Left atrial thrombus resolution in non-valvular atrial fibrillation or flutter: biomarker substudy results from a prospective study with rivaroxaban (X-TRA).

BACKGROUND: Non-vitamin K antagonist oral anticoagulants including rivaroxaban are widely used for stroke prevention in patients with atrial fibrillation (AF). We investigated the relationship between plasma biomarkers (indicative of thrombogenesis, fibrinolysis and inflammation) and left atrial thrombus resolution after rivaroxaban treatment. METHODS: This was an ancillary analysis of the X-TRA study, which was a prospective interventional study evaluating the use of rivaroxaban for left atrial/left atrial appendage (LA/LAA) thrombus resolution in AF patients. We assessed various biomarkers of thrombogenesis/fibrinolysis [D-dimer, plasminogen activator inhibitor-1 (PAI-1), prothrombin fragment 1 + 2 (F1,2), thrombin-antithrombin (TAT) complexes, von Willebrand factor (vWF)] and inflammation [high-sensitivity interleukin-6 (hsIL-6), and high-sensitivity C-reactive protein (hsCRP)], measured at baseline and after 6 weeks' of rivaroxaban treatment. RESULTS: There was a significant decrease in the mean levels of hsCRP, D-dimer, vWF, and TAT from baseline to end of treatment with rivaroxaban. Although none of the thrombogenesis/fibrinolysis biomarkers showed a significant relationship with thrombus resolution, high inflammatory biomarkers at baseline were significantly associated with an increased chance of the thrombus being completely resolved (hsIL-6) or reduced/resolved (hsCRP). CONCLUSIONS: Biomarkers of inflammation are significantly associated with LA/LAA thrombus outcomes in AF patients prospectively treated with rivaroxaban.

Is von Willebrand factor associated with stroke and death at mid-term in patients with non-valvular atrial fibrillation?

BACKGROUND: Heart failure and atrial fibrillation share common mechanisms that may contribute to hypercoagulability and thrombotic risk. Elevated von Willebrand factor (vWF) concentration has been associated with increased risk of thromboembolism and cardiovascular events. AIM: To investigate whether increased vWF plasma concentration predicts occurrence of a composite endpoint (all-cause death and stroke) in patients with non-valvular atrial fibrillation (NVAF). METHODS: We prospectively studied 122 patients (mean age 70±14years; 46% men) hospitalized with NVAF, and followed over a median (interquartile range) of 5.4 (2.3-9.0)years. Cox proportional models were used to estimate the association of vWF concentration with time to stroke and death. RESULTS: Forty-three patients (35%) had at least a stroke or died during the 5-year follow-up. Kaplan-Meier curves using vWF plasma concentration tertiles (≤191IU/dL;>191 to≤295IU/dL;>295IU/dL) showed that vWF plasma concentrations discriminated groups of patients with higher cardiovascular event rates (log-rank P=0.01). In the multivariable analysis, higher vWF concentrations (middle tertile hazard ratio [HR] 4.59, 95% confidence interval [CI] 1.55-13.50 [P=0.006]; upper tertile HR 4.10, 95% CI 1.43-11.75 [P=0.009]), age≥75years (HR 5.02, 95% CI 1.53-16.49; P=0.008), heart failure (HR 2.05, 1.01-4.19; P=0.048), C-reactive protein, log2 per unit increase (HR 1.29, 95% CI 1.04-1.61; P=0.021), no warfarin at discharge (HR 4.96, 95% CI 2.02-12.20; P<0.0001) and no aspirin at discharge (HR 4.41, 95% CI 1.71-11.97; P=0.002) were independently associated with an increased risk of stroke and all-cause death, whereas female sex was a protective factor (HR 0.35, 0.16-0.78; P=0.01). CONCLUSIONS: High vWF plasma concentrations may discriminate patients with NVAF at greater risk of stroke or all-cause death.

Periprocedural management of anticoagulation for atrial fibrillation catheter ablation in direct oral anticoagulant-treated patients.

BACKGROUND: Guidelines recommend performing atrial fibrillation (AF) catheter ablation without interruption of a direct oral anticoagulants (DOACs) and to administer unfractionated heparin (UFH) for an activated clotting time (ACT) ≥300 seconds, by analogy with vitamin K antagonist (VKA). Nevertheless, pharmacological differences between DOACs and VKA, especially regarding ACT sensitivity and UFH response, prevent extrapolation from VKA to DOACs. HYPOTHESIS: The level of anticoagulation at the time of the procedure in uninterrupted DOAC-treated patients is unpredictable and would complicate intraprocedural UFH administration and monitoring. METHODS: This prospective study included interrupted DOAC-treated patients requiring AF ablation. Preprocedural DOAC concentration ([DOAC]), intraprocedural UFH administration, and ACT values were recorded. A cohort of DOAC-treated patients requiring flutter catheter ablation was considered to illustrate [DOAC] without DOAC interruption. RESULTS: Forty-eight patients underwent AF and 14 patients underwent flutter ablation, respectively. In uninterrupted DOAC-treated patients, [DOAC] ranged from ≤30 to 466 ng/mL. When DOAC were interrupted, from 54 to 218 hours, [DOAC] were minimal (maximum: 36 ng/mL), preventing DOAC-ACT interference. Anyway, ACT values were poorly correlated with UFH doses (R 2 = 0.2256). CONCLUSIONS: Our data showed that uninterrupted DOAC therapy resulted in an unpredictable and highly variable initial level of anticoagulation before catheter ablation. Moreover, even with DOAC interruption preventing interference between DOAC, UFH, and ACT, intraprocedural UFH monitoring was complex. Altogether, our exploratory results call into question the appropriateness of transposing UFH dose protocols, as well as the relevance of ACT monitoring in uninterrupted DOAC-treated patients.

Significance of High-Sensitivity Troponin T After Elective External Direct Current Cardioversion for Atrial Fibrillation or Atrial Flutter.

External transthoracic direct current (DC) cardioversion is a commonly used method of terminating cardiac arrhythmias. Previous research has shown that DC cardioversion resulted in myocardial injury as evidenced by increased levels of cardiac troponin, even though only minimally. Many of these studies were based on the outdated monophasic defibrillators and older, less sensitive troponin assays. This study aimed to assess the effect of external transthoracic DC cardioversion on myocardial injury as measured by the change in the new high-sensitivity cardiac troponin T (hs-cTnT) using the more modern biphasic defibrillators. Patients who were admitted for elective DC cardioversion for atrial fibrillation or atrial flutter were recruited. Hs-cTnT levels were taken before cardioversion and at 6 hours after cardioversion. A total of 120 cardioversions were performed. Median (twenty-fifth to seventy-fifth interquartile range) cumulative energy was 161 J (155 to 532 J). A total of 49 (41%) patients received a cumulative energy of 300 J or higher. The median hs-cTnT level before cardioversion was 7 ng/L (4 to 11 ng/L) and that after cardioversion was 7 ng/L (4 to 10 ng/L). A Wilcoxon signed-rank test showed no significant difference between pre- and post-cardioversion hs-cTnT levels (Z = -0.940, p = 0.347). In conclusion, external DC cardioversion did not result in myocardial injury within the first 6 hours as measured by high-sensitivity troponin T. Patients who are cardioverted and are found to have a significant increase in cardiac troponin after cardioversion should be assessed for causes of myocardial injury and not assumed to have myocardial injury due to the cardioversion itself.

Design and rationale for the WARFA trial: a randomized controlled cross-over trial testing the therapeutic equivalence of branded and generic warfarin in atrial fibrillation patients in Brazil.

BACKGROUND: Warfarin is a commonly used anticoagulant. Whether a given dose of the different formulations of Brazilian warfarin will result in the same effect on the international normalized ratio (INR) is uncertain. The aim of the WARFA trial is to determine whether the branded and two generic warfarins available in Brazil differ in their effect on the INR. METHODS: WARFA is a cross-over RCT comparing three warfarins. The formulations tested are the branded Marevan® (Uniao Quimica/Farmoquimica) and two generic warfarin (manufactured respectively by Uniao Quimica Farmaceutica Nacional and Laboratorio Teuto Brasileiro). All of them were manufactured in Brazil, are available in all settings of the Brazilian healthcare system and were purchased from retail drugstores. Eligible participants had atrial fibrillation or flutter, had been using warfarin for at least 2 months with a therapeutic range of 2.0-3.0 and had low variability in INR results during the 1st period of the trial. Our primary outcome, for which we have an equality hypothesis, is the difference between warfarins in the mean absolute difference between two INR results, obtained after three and 4 weeks with each drug. Our secondary outcomes, that will be tested for inequality (except for the mean INR, which will be tested for equality), include the difference in the warfarin dose, and time in therapeutic range. Clinical events and adherence were also recorded and will be reported. DISCUSSION: To our knowledge, WARFA will be the first comparison of the more readily applicable INR results between branded and generic warfarins in Brazil. WARFA is important because warfarins are commonly switched between in the course of a chronic treatment in Brazil. Final results of WARFA are expected in May 2017. TRIAL REGISTRATION: ClinicalTrials.gov NCT02017197 . Registered 11 December 2013.

Influence of atrial fibrillation on post-discharge natriuretic peptide trajectory and clinical outcomes among patients hospitalized for heart failure: insights from the ASTRONAUT trial.

AIMS: Change in NT-proBNP level is a common surrogate endpoint in early phase heart failure (HF) trials, but whether this endpoint is influenced by atrial fibrillation/flutter (AFF) is unclear. METHODS AND RESULTS: This analysis included 1358 patients from the ASTRONAUT trial, which randomized patients hospitalized for HF with EF ≤40% to aliskiren or placebo in addition to standard care. Patients were stratified by presence of AFF on baseline ECG. NT-proBNP was measured longitudinally by a core laboratory at baseline, 1 month, 6 months, and 12 months. Compared with non-AFF patients, AFF patients experienced greater reduction from baseline in log-transformed NT-proBNP (interaction P < 0.001), but this difference was not significant after adjustment (interaction P = 0.726). The ability of aliskiren to lower NT-proBNP during follow-up differed by AFF status (interaction P = 0.001), with aliskiren lowering NT-proBNP more than placebo among non-AFF patients only. After adjustment, baseline AFF was not associated with mortality or HF hospitalization at 12 months (all P ≥ 0.152). CONCLUSION: In this hospitalized HF cohort, AFF status did not influence post-discharge NT-proBNP trajectory or clinical outcomes after adjustment for patient characteristics. Aliskiren lowered follow-up NT-proBNP levels in patients without AFF, but had no influence among patients with AFF. This study generates the hypothesis that the ability of a HF trial to meet an NT-proBNP defined endpoint may be influenced by the prevalence of AFF in the population. Because aliskiren did not improve outcomes in patients without AFF, this analysis suggests changes in NT-proBNP induced by investigational therapies may be dissociated from clinical effects.

Myocardial injury during radiofrequency and cryoablation of typical atrial flutter.

PURPOSE: Cardiac enzyme elevation after radiofrequency (RF) catheter ablation of atrial flutter (AFL) is common. Some studies found that cryoablation (CRYO) of AFL, compared to RF, is associated with higher levels of troponin, a finding that may indicate CRYO causes a greater amount of myocardial injury than RF. However, other investigations found no significant differences between troponin levels after CRYO versus RF. We have in a randomized study compared the post-procedural troponin I levels in RF and CRYO and the possible relation to procedural outcome and complications. METHODS: We randomized 153 patients with cavotricuspid isthmus (CTI)-dependent AFL to CRYO or RF (78 CRYO; 75 RF). RF was performed with a 3.5-mm open-irrigated-tip catheter, and CRYO was performed with an 8-mm-tip catheter. Troponin I levels were measured before and 6 h after ablation. RESULTS: Acute procedural success was achieved in 71/75 patients in the RF and in 72/78 patients in the CRYO. Troponin I levels were significantly elevated in both groups (baseline 0.012, 6th hour 0.35 ng/ml; p < 0.001). Troponin I levels were similar for RF and CRYO. Troponin I levels were higher in patients with acute failure compared to patients with acute success (0.48 ± 0.4 and 0.34 ± 0.16 ng/ml, p = 0.029); however, there was no difference between patients with or without late recurrence. There were no major complications in any group. CONCLUSION: RF and CRYO for CTI-dependent AFL resulted in similar amounts of procedural myocardial injury. Troponin I levels had no prognostic value for late recurrence of AFL and there were no complications related to high troponin I levels.

The role of digitalis pharmacokinetics in converting atrial fibrillation and flutter to regular sinus rhythm.

This report examined the role of digitalis pharmacokinetics in helping to guide therapy with digitalis glycosides with regard to converting atrial fibrillation (AF) or flutter to regular sinus rhythm (RSR). Pharmacokinetic models of digitoxin and digoxin, containing a peripheral non-serum effect compartment, were used to analyze outcomes in a non-systematic literature review of five clinical studies, using the computed concentrations of digitoxin and digoxin in the effect compartment of these models in an analysis of their outcomes. Four cases treated by the author were similarly examined. Three literature studies showed results no different from placebo. Dosage regimens achieved ≤11 ng/g in the model's peripheral compartment. However, two other studies achieved significant conversion to RSR. Their peripheral concentrations were 9-14 ng/g. In the four patients treated by the author, three converted using classical clinical titration with incremental doses, plus therapeutic drug monitoring and pharmacokinetic guidance from the models for maintenance dosage. They converted at peripheral concentrations of 9-18 ng/g, similar to the two studies above. No toxicity was seen. Successful maintenance was achieved, using the models and their pharmacokinetic guidance, by giving somewhat larger than average recommended dosage regimens in order to maintain peripheral concentrations present at conversion. The fourth patient did not convert, but only reached peripheral concentrations of 6-7 ng/g, similar to the studies in which conversion was no better than placebo. Pharmacokinetic analysis and guidance play a highly significant role in converting AF to RSR. To the author's knowledge, this has not been specifically described before. In my experience, conversion of AF or flutter to RSR does not occur until peripheral concentrations of 9-18 ng/g are reached. Results in the four cases correlated well with the literature findings. More work is needed to further evaluate these provocative findings.

Factors affecting the development of atrial fibrillation and atrial flutter (AF/AFL) following autologous hematopoietic SCT (auto-HSCT).

The use of autologous hematopoietic SCT (auto-HSCT) has expanded to include older patients. Increasing age is a well-appreciated risk factor for the development of atrial fibrillation and/or atrial flutter (AF/AFL) in the general population. As more elderly patients undergo auto-HSCT, the risk of developing AF/AFL post transplant may also increase. However, few data evaluating other risk factors for the development of AF/AFL following auto-HSCT exist. Therefore, we performed a retrospective study to determine the incidence of AF/AFL following auto-HSCT and to determine the risk factors associated with the development of AF/AFL. Patients who developed AF/AFL were compared with a group of patients who received auto-HSCT within the same time period (April 1999 to May 2005) and were within 5 years of age. Of the 516 patients who underwent auto-HSCT at the University of Nebraska Medical Center 44 (8.5%) developed AF/AFL at a median time of 4 days (range, days 1-9) following auto-HSCT. In multivariate analysis, risk factors for developing AF/AFL were older age, odds ratio and 95% CI of 1.14 (1.07-1.21), elevated serum creatinine level, 2.69 (1.00-7.22), history of previous arrhythmia, 9.33 (3.01-28.99), and history of previous mediastinal irradiation, 11.12 (1.33-92.96).

Comparison of pro-atrial natriuretic peptide and atrial remodeling in marathon versus non-marathon runners.

Long-term endurance sports are associated with atrial remodeling and an increased risk for atrial fibrillation (AF) and atrial flutter. Pro-atrial natriuretic peptide (pro-ANP) is a marker of atrial wall tension and elevated in patients with AF. The aim of this study was to test the hypothesis that atrial remodeling would be perpetuated by repetitive episodes of atrial stretching during strenuous competitions, reflected by elevated levels of pro-ANP. A cross-sectional study was performed on nonelite runners scheduled to participate in the 2010 Grand Prix of Bern, a 10-mile race. Four hundred ninety-two marathon and nonmarathon runners applied for participation, 70 were randomly selected, and 56 entered the final analysis. Subjects were stratified according to former marathon participations: a control group (nonmarathon runners, n = 22), group 1 (1 to 4 marathons, n = 16), and group 2 (≥5 marathons, n = 18). Results were adjusted for age, training years, and average weekly endurance training hours. The mean age was 42 ± 7 years. Compared to the control group, marathon runners in groups 1 and 2 had larger left atria (25 ± 6 vs 30 ± 6 vs 34 ± 7 ml/m(2), p = 0.002) and larger right atria (27 ± 7 vs 31 ± 8 vs 35 ± 5 ml/m(2), p = 0.024). Pro-ANP levels at baseline were higher in marathon runners (1.04 ± 0.38 vs 1.42 ± 0.74 vs 1.67 ± 0.69 nmol/L, p = 0.006). Pro-ANP increased significantly in all groups after the race. In multiple linear regression analysis, marathon participation was an independent predictor of left atrial (ß = 0.427, p <0.001) and right atrial (ß = 0.395, p = 0.006) remodeling. In conclusion, marathon running was associated with progressive left and right atrial remodeling, possibly induced by repetitive episodes of atrial stretching. The altered left and right atrial substrate may facilitate atrial arrhythmias.

Multiple shocks affect thoracic electrical impedance during external cardioversion of atrial fibrillation.

BACKGROUND: Thoracic impedance (TI) influences the success of external cardioversion (ECV) or defibrillation because current intensity traversing the heart is inversely related to TI. Experimental data suggest that TI decreases after multiple shocks. We undertook a clinical study to determine changes of TI values in patients with atrial fibrillation or flutter requiring ECV. METHODS: We enrolled 222 consecutive patients (age 73 +/- 11 years; males 67%; body weight 75 +/- 13 kg) who underwent ECV between January 2004 and February 2007. Biphasic shocks were delivered through adhesive pads placed in the anteroposterior position. The initial energy was set at 1 J/kg, with progressive increases up to a maximum of 180 J in case of failure. In the last 39 elective patients, plasma concentration of interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha were determined before and 6 hours after ECV. RESULTS: Sinus rhythm was restored in 202 patients (91.0%). Of these, 155 (69.8%) required more than one shock (on average, 2.5 +/- 1.5 shocks/patient). Final values of energy and peak current intensity were 136 +/- 47 J and 50 +/- 14 A, respectively. TI decreased significantly by 6.2% from baseline after > or =2 shocks (P < 0.001). The absolute reduction was correlated with baseline TI, number of delivered shocks, and hemoglobin oxygen saturation. IL-6 and TNF-alpha increased with ECV (P < 0.001 and P = 0.014, respectively). CONCLUSIONS: TI decreases significantly after multiple shocks, possibly by activation of acute inflammation.

[Influence of electrical cardioversion on troponine I and brain natriuretic peptide (NT-proBNP) levels in patients with persistent atrial fibrillation/flutter]. / Utjecaj elektrokonverzije na vrijednosti troponina I i mozdanog natriuretskog peptida (NT-proBNP) u bolesnika s perzistentnom fibrilacijom/undulacijom atrija.

The goal of our research was to determine how electrical cardioversion influences troponine I and brain natriuretic peptide (NT-proBNP) levels in patients with persistent atrial fibrillation (AF), without heart failure. Reaserch was conducted on 20 patients with AF. Before and after cardioversion levels of troponine I, creatine-kinase (CK), lactate-dehydrogenase (LDH) and brain natriuretic peptide (NT-proBNP) were measured. Average total applied energy was 344,2 +/- 268,9 Joule. After cardioversion CK level was insignificantly higher (113,3:259,0). Levels of troponine I did not change significantly after cardioversion (0,185:0,202). By measuring levels of NT-proBNP significantly lower levels of NT-proBNP were found after cardioversion (1095:432). There was a strong correlation between the duration of arrhythmia and the NT-proBNP level. Electrical cardioversion with standard recommended energy does not cause significant myocardial lesion. CK level elevation is a consequence of skeletal muscle lesion. Possible elevation of troponine I should be interpreted by another etiology. Increased production of BNP is caused by increased pressure and volume overload of the atrium, in patients with AF, independent of global cardiac function, according to that we think that in patients with AF discriminatory values of BNP in heart failure diagnostics should be corrected to higher levels.