A decade of catheter ablation of cardiac arrhythmias in Sweden: ablation practices and outcomes.

AIMS: Catheter ablation is considered the treatment of choice for many tachyarrhythmias, but convincing 'real-world' data on efficacy and safety are lacking. Using Swedish national registry data, the ablation spectrum, procedural characteristics, as well as ablation efficacy and reported adverse events are reported. METHODS AND RESULTS: Consecutive patients (≥18 years of age) undergoing catheter ablation in Sweden between 01 January 2006 and 31 December 2015 were included in the study. Follow-up (repeat ablation and vital status) was collected through 31 December 2016. A total of 26 642 patients (57 ± 15 years, 62% men), undergoing a total of 34 428 ablation procedures were included in the study. In total, 4034 accessory pathway/Wolff-Parkinson-White syndrome (12%), 7358 AV-nodal re-entrant tachycardia (21%), 1813 atrial tachycardia (5.2%), 5481 typical atrial flutter (16%), 11 916 atrial fibrillation (AF, 35%), 2415 AV-nodal (7.0%), 581 premature ventricular contraction (PVC, 1.7%), and 964 ventricular tachycardia (VT) ablations (2.8%) were performed. Median follow-up time was 4.7 years (interquartile range 2.7-7.0). The spectrum of treated arrhythmias changed over time, with a gradual increase in AF, VT, and PVC ablation (P < 0.001). Decreasing procedural times and utilization of fluoroscopy with time, were seen for all arrhythmia types. The rates of repeat ablation differed between ablation types, with the highest repeat ablation seen in AF (41% within 3 years). The rate of reported adverse events was low (n = 595, 1.7%). Death in the immediate period following ablation was rare (n = 116, 0.34%). CONCLUSION: Catheter ablations have shifted towards more complex procedures over the past decade. Fluoroscopy time has markedly decreased and the efficacy of catheter ablation seems to improve for AF.

Higher burden of supraventricular ectopic complexes early after catheter ablation for atrial fibrillation is associated with increased risk of recurrent atrial fibrillation.

Aims: Early identification of patients who could benefit from early re-intervention after catheter ablation is highly warranted. Our aim was to investigate the association between post-procedural burden of supraventricular ectopic complexes (SVEC) and the risk of long-term atrial fibrillation (AF) recurrence. Methods and results: A total of 125 patients undergoing catheter ablation for AF were included. Patients underwent 7-day Holter recordings immediately post-procedural. The number of SVEC in post-procedural Holter recordings was categorized into quartiles: 0-72, 73-212, 213-782 and ≥ 783 SVEC/day. Long-term AF recurrence was defined as a combined endpoint of AF ≥ 1 min during follow-up Holter recordings, cardioversion or hospitalization for AF after a 3-month blanking period and within 24 months of follow-up. High post-procedural supraventricular ectopy burden was associated with an increased risk of long-term AF recurrence in a dose-dependent manner (≥ 783 SVEC: HR 4.6 [1.9-11.5], P < 0.001) irrespective of AF recurrence during the blanking period or other risk factors. In patients with early AF recurrence < 90 days after catheter ablation ectopy burden was also highly predictive of long-term AF recurrence (SVEC ≥ 213: HR 3.0 [1.3-6.7], P = 0.007). Correspondingly, patients with early AF recurrence but low ectopy burden remained at low risk of long-term AF recurrence after the blanking period. Conclusion: Our results indicate that post-procedural ectopy burden is highly associated with long-term AF recurrence and could be a potent risk marker for selection of patients for early re-ablation. Development of future ablation risk stratification and strategies should include focus on post-procedural ectopy burden.

Pre- and postoperative atrial fibrillation in CABG patients have similar prognostic impact.

OBJECTIVES: To study pre- and postoperative atrial fibrillation and its long-term effects in a cohort of aortocoronary bypass surgery patients. DESIGN: Altogether 615 patients undergoing aortocoronary bypass graft surgery in 1999-2000 were studied. Forty-four (7%) had preoperative atrial fibrillation. Postoperative atrial fibrillation occurred in 165/615 patients (27%) while 406/615 patients (66%) had no atrial fibrillation. After a median follow-up of 15 years, symptoms and medication in survivors were recorded, and cause of death in the deceased was obtained. RESULTS: Death due to cerebral ischaemia was most common in the pre- and postoperative atrial fibrillation groups (7% and 5%, respectively, v. 2% among those without atrial fibrillation, p = .038), as were death due to heart failure (18% and 14%, v. 7%, p = .007) and sudden death (9% and 5%, v. 2%, p = .029). The presence of pre- or postoperative atrial fibrillation was an independent risk factor for late mortality (hazard ratios 1.47 (1.02-2.12) and 1.28 (1.01-1.63), respectively). CONCLUSIONS: Patients with pre- or postoperative atrial fibrillation undergoing aortocoronary bypass surgery have increased long-term mortality and risk of cerebral ischemic and cardiovascular death compared with patients in sinus rhythm.

Catheter ablation for atrial fibrillation is associated with lower incidence of stroke and death: data from Swedish health registries.

AIM: It is unclear if catheter ablation for atrial fibrillation (AF) affects the prognosis or merely is a symptomatic treatment. The aim is to study the association between ablation for AF, ischaemic stroke, and mortality. METHODS AND RESULTS: We identified all 361 913 patients with a diagnosis of AF in the Swedish Patient Register. During a 7-year period, 5176 AF ablations were performed among 4278 individuals. Patients who had undergone catheter ablation were younger (58.7 vs. 74.7 years, P < 0.001) and healthier (mean CHA2DS2-VASc scores 1.5 ± 1.4 vs. 3.6 ± 1.9, P < 0.001) than other patients with AF. Propensity score matching was used to construct two cohorts of equal size (n = 2836) with similar characteristics in 51 dimensions. Mean follow-up was 4.4 ± 2.0 years (minimum 1 year). In the ablated group, 78 patients suffered ischaemic stroke compared with 112 in the non-ablated (annual rates 0.70 vs. 1.0%, P = 0.013). A total of 88 ablated and 184 non-ablated patients died (annual rates 0.77 vs. 1.62%, P < 0.001). After multivariable adjustments, catheter ablation was associated with lower risk of ischaemic stroke [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.51-0.93) and with lower mortality risk (HR 0.50, 95% CI 0.37-0.62). Stroke reduction was most pronounced among patients with CHA2DS2-VASc score ≥2 (HR 0.39, 95% CI 0.19-0.78) and among patients without new cardioversions beyond 6 months after the ablation (HR 0.68, 95% CI 0.48-0.97). CONCLUSION: Ablation may be associated with lower incidence of ischaemic stroke and death in patients with AF. This beneficial finding appears more pronounced in patients with higher thromboembolic risk.

Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation.

BACKGROUND: There are limited data comparing radiofrequency catheter ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation. METHODS: We randomly assigned 294 patients with paroxysmal atrial fibrillation and no history of antiarrhythmic drug use to an initial treatment strategy of either radiofrequency catheter ablation (146 patients) or therapy with class IC or class III antiarrhythmic agents (148 patients). Follow-up included 7-day Holter-monitor recording at 3, 6, 12, 18, and 24 months. Primary end points were the cumulative and per-visit burden of atrial fibrillation (i.e., percentage of time in atrial fibrillation on Holter-monitor recordings). Analyses were performed on an intention-to-treat basis. RESULTS: There was no significant difference between the ablation and drug-therapy groups in the cumulative burden of atrial fibrillation (90th percentile of arrhythmia burden, 13% and 19%, respectively; P=0.10) or the burden at 3, 6, 12, or 18 months. At 24 months, the burden of atrial fibrillation was significantly lower in the ablation group than in the drug-therapy group (90th percentile, 9% vs. 18%; P=0.007), and more patients in the ablation group were free from any atrial fibrillation (85% vs. 71%, P=0.004) and from symptomatic atrial fibrillation (93% vs. 84%, P=0.01). One death in the ablation group was due to a procedure-related stroke; there were three cases of cardiac tamponade in the ablation group. In the drug-therapy group, 54 patients (36%) underwent supplementary ablation. CONCLUSIONS: In comparing radiofrequency ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation, we found no significant difference between the treatment groups in the cumulative burden of atrial fibrillation over a period of 2 years. (Funded by the Danish Heart Foundation and others; MANTRA-PAF ClinicalTrials.gov number, NCT00133211.).

The cost-effectiveness of radiofrequency catheter ablation as first-line treatment for paroxysmal atrial fibrillation: results from a MANTRA-PAF substudy.

AIM: The aim of this prospective substudy was to estimate the cost-effectiveness of treating paroxysmal atrial fibrillation (AF) with radiofrequency catheter ablation (RFA) compared with antiarrhythmic drugs (AADs) as first-line treatment. METHODS AND RESULTS: A decision-analytic Markov model, based on MANTRA-PAF (Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation) study data, was developed to study long-term effects and costs of RFA compared with AADs as first-line treatment. Positive clinical effects were found in the overall population, a gain of an average 0.06 quality-adjusted life years (QALYs) to an incremental cost of €3033, resulting in an incremental cost-effectiveness ratio of €50 570/QALY. However, the result of the subgroup analyses showed that RFA was less costly and more effective in younger patients. This implied an incremental cost-effectiveness ratio of €3434/QALY in ≤50-year-old patients respectively €108 937/QALY in >50-year-old patients. CONCLUSION: Radiofrequency catheter ablation as first-line treatment is a cost-effective strategy for younger patients with paroxysmal AF. However, the cost-effectiveness of using RFA as first-line therapy in older patients is uncertain, and in most of these AADs should be attempted before RFA (MANTRA-PAF ClinicalTrials.gov number; NCT00133211).

The impact of asbestos exposure in Swedish construction workers.

OBJECTIVE: To study the occurrence of pleural mesothelioma as a measure of the impact on health from asbestos exposure in the construction industry. METHODS: The occurrence of pleural mesothelioma in different occupations, time periods and birth cohorts was studied in a cohort of construction workers. They were prospectively followed after they had participated in health examinations between 1971 and 1993. The analysis was restricted to men and in total 367,568 men was included in the analysis. RESULTS: In total there were 419 cases of pleural mesotheliomas between 1972 and 2009. As expected the age adjusted incidence was high in insulation workers and plumbers (39 and 16 cases per 100,000 person-years, respectively). However, only 21% of the pleural mesotheliomas occurred in those occupational groups. Occupational groups with many cases of pleural mesothelioma were concrete workers (N = 56), wood workers (N = 55), painters (N = 32), electricians (N = 48), and foremen (N = 37). The highest risk was in birth cohorts born between 1935 and 1945. Between 1995 and 2009 around one-third of all male cases in the country occurred in this birth cohort. The risk seemed to decrease considerably in men born after 1955. CONCLUSION: In Sweden a considerable proportion of pleural mesotheliomas occur among construction workers; and not only in jobs traditionally associated with asbestos exposure such as insulators and plumbers but also among electricians, for example. The results shows that asbestos exposure occurs in many occupational groups, indicating that safe handling of asbestos is a very difficult or even impossible task in the construction industry.

Procedural efficiency is enhanced combining the pentaspline pulsed field ablation catheter with three-dimensional electroanatomical mapping system for pulmonary vein isolation.

BACKGROUND: Pulsed field ablation (PFA) offers a safe, non-thermal alternative for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). Currently, the pentaspline PFA-system relies heavily on fluoroscopy for catheter manipulation, which poses challenges due to the complexity of left atrium anatomy. Incorporating three-dimensional electroanatomical mapping (3D-EAM) could improve procedural efficiency reducing dependency on fluoroscopy guidance. This study aims to evaluate the effects of integration of 3D-EAM with PFA during PVI. METHODS: Between September 2022 and December 2023, we retrospectively enrolled 248 patients with paroxysmal or persistent AF undergoing PVI at our center using the pentaspline PFA catheter. The control group (n = 104) received conventional PFA with fluoroscopic guidance alone, while the intervention group (n = 144) underwent PVI with PFA with 3D-EAM integration. Primary outcomes were procedural time, fluoroscopy time (FT), and dose area product (DAP). Secondary endpoints included acute procedural success and incidence of periprocedural complications. RESULTS: In the 3D-EAM-PFA group, procedural time was 63.3 ± 14.3 min, compared to 65.6 ± 14.9 min in the control group (p = 0.22). The 3D-EAM group experienced significantly reduced FT (9.7 ± 4.4 min vs. 16.7 ± 5.2 min) and DAP (119.2 ± 121.7 cGycm2 vs. 338.7 ± 229.9 cGycm2) compared to the control group, respectively (p < 0.001). Acute procedural success was achieved in all cases. No major complications were observed in either group. CONCLUSION: Integration of 3D-EAM with the pentaspline PFA catheter for PVI in AF treatment offers a promising approach, with significantly reduced fluoroscopy exposure without compromising procedural time and efficacy.

Intestinal expression profiles and hepatic expression of LEAP2, ghrelin and their common receptor, GHSR, in humans.

Liver-expressed antimicrobial peptide 2 (LEAP2) and ghrelin have reciprocal effects on their common receptor, the growth hormone secretagogue receptor (GHSR). Ghrelin is considered a gastric hormone and LEAP2 a liver-derived hormone and both have been proposed to be involved in the pathophysiology of obesity and type 2 diabetes (T2D). We investigated the mRNA expression of LEAP2, ghrelin and GHSR along the intestinal tract of individuals with and without TD2, and in the liver of men with and without obesity. Mucosal biopsies retrieved with 30-cm intervals throughout the small intestine and from 7 well-defined locations along the large intestine from 12 individuals with T2D and 12 healthy controls together with liver biopsies from 15 men with obesity and 15 lean men were subjected to bulk transcriptomics analysis. Both in individuals with and without T2D, mRNA expression of LEAP2 increased through the small intestine until dropping at the ileocecal valve, with little LEAP2 mRNA expression in the large intestine. Pronounced LEAP2 expression was observed in the liver of men with and without obesity. Robust ghrelin mRNA expression was observed in the duodenum of individuals with and without T2D, gradually decreasing along the small intestine with little expression in the large intestine. Ghrelin mRNA expression was not detected in the liver biopsies, and GHSR mRNA expression was not. In conclusion, we provide unique mRNA expression profiles of LEAP2, ghrelin and GHSR along the human intestinal tract showing no T2D-associated changes, and in the liver showing no differences between men with and without obesity.

Association between catheter ablation of atrial fibrillation and mortality or stroke.

OBJECTIVE: Catheter ablation of atrial fibrillation effectively reduces symptomatic burden. However, its long-term effect on mortality and stroke is unclear. We investigated if patients with atrial fibrillation who undergo catheter ablation have lower risk for all-cause mortality or stroke than patients who are managed medically. METHODS: We retrospectively included 5628 consecutive patients who underwent first-time catheter ablation for atrial fibrillation between 2008 and 2018 at three major Swedish electrophysiology units. Control individuals with an atrial fibrillation diagnosis but without previous stroke were selected from the Swedish National Patient Register, resulting in a control group of 48 676 patients. Propensity score matching was performed to produce two cohorts of equal size (n=3955) with similar baseline characteristics. The primary endpoint was a composite of all-cause mortality or stroke. RESULTS: Patients who underwent catheter ablation were healthier (mean CHA2DS2-VASc score 1.4±1.4 vs 1.6±1.5, p<0.001), had a higher median income (288 vs 212 1000 Swedish krona [KSEK]/year, p<0.001) and had more frequently received university education (45.1% vs 28.9%, p<0.001). Mean follow-up was 4.5±2.8 years. After propensity score matching, catheter ablation was associated with lower risk for the combined primary endpoint (HR 0.58, 95% CI 0.48 to 0.69). The result was mainly driven by a decrease in all-cause mortality (HR 0.51, 95% CI 0.41 to 0.63), with stroke reduction showing a trend in favour of catheter ablation (HR 0.75, 95% CI 0.53 to 1.07). CONCLUSIONS: Catheter ablation of atrial fibrillation was associated with a reduction in the primary endpoint of all-cause mortality or stroke. This result was driven by a marked reduction in all-cause mortality.

[Pulsed Field Ablation shows promise - Experiences from the first 100 patients in Sweden]. / Pulsfältablation verkar lovande ­ står vi inför ett paradigmskifte?

Pulmonary vein isolation (PVI) of symptomatic atrial fibrillation is an effective method of maintaining sinus rhythm. Radiofrequency ablation and cryotechnology have been used for this purpose for many years. One disadvantage of these methods is the risk of serious complications such as pulmonary vein stenosis, phrenic nerve palsy and atrio-oesophageal fistula. Pulsed Field Ablation (PFA) is a promising ablation modality for treatment of atrial fibrillation. This technique employs a train of high amplitude electrical pulses with short duration that ablate myocardium with minimal effect on surrounding tissues. 100 patients underwent PFA at the Capio Arrhythmia Center Stockholm. All pulmonary veins could be identified successfully and isolation could be achieved without difficulty. No serious complication during ablation and observation time after the procedure occurred. Our experience with PFA shows that PVI with this technique in symptomatic atrial fibrillation is a safe and effective method.

Sudden cardiac arrest associated with early repolarization.

BACKGROUND: Early repolarization is a common electrocardiographic finding that is generally considered to be benign. Its potential to cause cardiac arrhythmias has been hypothesized from experimental studies, but it is not known whether there is a clinical association with sudden cardiac arrest. METHODS: We reviewed data from 206 case subjects at 22 centers who were resuscitated after cardiac arrest due to idiopathic ventricular fibrillation and assessed the prevalence of electrocardiographic early repolarization. The latter was defined as an elevation of the QRS-ST junction of at least 0.1 mV from baseline in the inferior or lateral lead, manifested as QRS slurring or notching. The control group comprised 412 subjects without heart disease who were matched for age, sex, race, and level of physical activity. Follow-up data that included the results of monitoring with an implantable defibrillator were obtained for all case subjects. RESULTS: Early repolarization was more frequent in case subjects with idiopathic ventricular fibrillation than in control subjects (31% vs. 5%, P<0.001). Among case subjects, those with early repolarization were more likely to be male and to have a history of syncope or sudden cardiac arrest during sleep than those without early repolarization. In eight subjects, the origin of ectopy that initiated ventricular arrhythmias was mapped to sites concordant with the localization of repolarization abnormalities. During a mean (+/-SD) follow-up of 61+/-50 months, defibrillator monitoring showed a higher incidence of recurrent ventricular fibrillation in case subjects with a repolarization abnormality than in those without such an abnormality (hazard ratio, 2.1; 95% confidence interval, 1.2 to 3.5; P=0.008). CONCLUSIONS: Among patients with a history of idiopathic ventricular fibrillation, there is an increased prevalence of early repolarization.

Blood pressure, body size and prostate cancer risk in the Swedish Construction Workers cohort.

Data from prospective studies on blood pressure and prostate cancer risk are limited, and results are inconclusive. Baseline measurements of height, weight and blood pressure were available in 336,159 men in the Swedish Construction Workers cohort. During an average of 22.2 years of follow-up, 10,002 incident cases and 2,601 fatal cases of prostate cancer were identified in National registers. For 5,219 cases, tumor characteristics were available; 2,817 tumors were classified as nonaggressive and 2,402 as aggressive. Relative risks of disease were estimated from Cox regression models, using attained age as time-scale, and adjusting for birth year, smoking status and body mass index (BMI). Top compared to bottom quintile level of systolic or diastolic blood pressure was associated with a significant 15-20% decreased risk of incident prostate cancer (p for trend: systolic < 0.0001, diastolic = 0.3), but blood pressure was not significantly associated with risk of fatal prostate cancer. BMI was not associated with prostate cancer incidence, but was positively associated with fatal prostate cancer; men in the top quintile had a 30% increased risk (p for trend = 0.0004). The associations between blood pressure and BMI and nonaggressive tumors were similar to those of incident prostate cancer, and associations with aggressive tumors were similar to those of fatal prostate cancer. Data from our study suggest that hypertension is associated with a decreased risk of incident prostate cancer, but the explanation for this finding is unclear. Our study support a positive association between overweight and risk of fatal prostate cancer.

A randomized invasive cardiac electrophysiology study of the combined ion channel blocker AZD1305 in patients after catheter ablation of atrial flutter.

BACKGROUND: This study assessed the cardiac electrophysiological and hemodynamic effects of an intravenous infusion of the combined ion channel blocker AZD1305. METHODS: After successful ablation of atrial flutter, patients were randomized to receive placebo (n = 12) or AZD1305 (n = 38) in 4 ascending dose groups. Electrophysiological and hemodynamic measurements were performed before and commencing 20 minutes after start of infusion. RESULTS: Left atrial effective refractory period increased dose and the primary outcome measure increased dose and plasma concentration dependently, with a mean increase of 55 milliseconds in dose group 3. There was a corresponding increase in right atrial effective refractory period of 84 milliseconds. The right ventricular effective refractory period and the paced QT interval also increased dose and concentration dependently, by 59 and 70 milliseconds, respectively, in dose group 3. There were indications of moderate increases of atrial, atrioventricular nodal, and ventricular conduction times. No consistent changes in intracardiac pressures were observed, but there was a small transient decrease in systolic blood pressure. Adverse events were consistent with the study population and procedure, and there were no signs of proarrhythmia despite marked delay in ventricular repolarization in some individuals. CONCLUSIONS: AZD1305 shows electrophysiological characteristics indicative of potential antiarrhythmic efficacy in atrial fibrillation.

Atorvastatin and persistent atrial fibrillation following cardioversion: a randomized placebo-controlled multicentre study.

AIMS: To evaluate the effect of atorvastatin in achieving stable sinus rhythm (SR) 30 days after electrical cardioversion (CV) in patients with persistent atrial fibrillation (AF). METHODS AND RESULTS: The study included 234 patients. The patients were randomized to treatment with atorvastatin 80 mg daily (n = 118) or placebo (n = 116) in a prospective, double-blinded fashion. Treatment was initiated 14 days before CV and was continued 30 days after CV. The two groups were well-balanced with respect to baseline characteristics. Mean age was 65 +/- 10 years, 76% of the patients were male and 4% had ischaemic heart disease. Study medication was well-tolerated in all patients but one. Before primary endpoint 12 patients were excluded. In the atorvastatin group 99 patients (89%) converted to SR at electrical CV compared with 95 (86%) in the placebo group (P = 0.42). An intention-to-treat analysis with the available data, by randomization group, showed that 57 (51%) in the atorvastatin group and 47 (42%) in the placebo group were in SR 30 days after CV (OR 1.44, 95%CI 0.85-2.44, P = 0.18). CONCLUSION: Atorvastatin was not statistically superior to placebo with regards to maintaining SR 30 days after CV in patients with persistent AF.

Effects of AZD0837, a novel direct thrombin inhibitor, on the electrophysiological properties of the human heart: a randomized, double-blind, parallel-group, placebo-controlled study.

BACKGROUND: AZD0837 is an investigational oral anticoagulant that is bioconverted to its active form, AR-H067637, a selective direct thrombin inhibitor. OBJECTIVES: The objectives of the present study were to investigate if there are any clinically relevant adverse effects of intravenous AZD0837 on cardiac conduction, refractoriness and repolarization, and to study its safety and tolerability. METHODS: In this randomized, double-blind, parallel-group, placebo-controlled study (study code D1250C00026), invasive electrophysiological measurements were performed twice in 30 subjects with a history of, or ongoing, atrial flutter, starting 30 minutes after successful ablation of atrial flutter and then 60 minutes after start of an intravenous infusion of AZD0837. Pre-study warfarin therapy was not an exclusion criterion. The stimulation protocol was performed mainly at 500 and 400 ms drive cycle length. A 12-lead ECG was also recorded before and during AZD0837 infusion. Plasma concentrations of AZD0837 and its metabolites were obtained at predefined timepoints. RESULTS: Measurements were made at baseline and during stable plasma concentrations of the prodrug AZD0837 (mean +/- standard deviation 7.96 +/- 2.38 micromol/L, approximate target of 10 micromol/L), the intermediate metabolite AR-H69927 (1.26 +/- 0.39 micromol/L, target 1-2 micromol/L) and the active direct thrombin inhibitor AR-H067637 (0.35 +/- 0.14 micromol/L, target 0.5-1.0 micromol/L). There were no clinically relevant effects on cardiac conduction (QRS duration, PR interval, His bundle electrogram, Wenckebach point), refractoriness (atrial, atrioventricular and ventricular effective refractory periods) or repolarization (QT, QT interval corrected for heart rate using Fridericia's formula, QRS onset to the top of the T wave [QT(top)], QRS onset to the end of the T wave [QT(end)] or QT(top) - QT(end)). CONCLUSIONS: AZD0837 was well tolerated, and had no clinically relevant effects on cardiac electrophysiology of the target population, either in subjects previously treated with warfarin or in those without previous treatment.

Patients with postoperative atrial fibrillation have a doubled cardiovascular mortality.

OBJECTIVES: To investigate the impact of postoperative AF on late mortality and cause of death in CABG patients. DESIGN: All CABG patients without preoperative AF surgically treated between January 1, 1997 and June 30, 2000 were included (N = 1419). Altogether, 419 patients (29.5%) developed postoperative AF. After a median follow-up of 8.0 years, survival data were obtained, causes of death were compared and Cox proportional hazard analysis was used to determine predictors of late mortality. RESULTS: The total mortality was 140 deaths/419 patients (33.4%) in postoperative AF patients and 191 deaths/1 000 patients (19.1%) in patients without AF. Death due to cerebral ischemia (2.6% vs. 0.5%), myocardial infarction (7.4% vs. 3.0%), sudden death (2.6% vs. 0.9%), and heart failure (6.7% vs. 2.7%) was more common among postoperative AF patients. Postoperative AF was an age-independent risk indicator for late mortality with a hazard ratio (HR) of 1.56 (95% confidence interval 1.23-1.98). CONCLUSIONS: Postoperative AF is an age-independent risk factor for late mortality in CABG patients, explained by an increased risk of cardiovascular death.

Risk of gastroesophageal cancer among smokers and users of Scandinavian moist snuff.

Although Scandinavian moist snuff ("snus"), no doubt, is a safer alternative to smoking, there is limited evidence against an association with gastroesophageal cancers. In a retrospective cohort study, we investigated esophageal and stomach cancer incidence among 336,381 male Swedish construction workers who provided information on tobacco smoking and snus habits within a health surveillance program between 1971 and 1993. Essentially complete follow-up through 2004 was accomplished through linkage to several nationwide registers. Multivariable Cox proportional hazards regression models estimated relative risks (RR) and 95% confidence intervals (CIs). Compared to never-users of any tobacco, smokers had increased risks for adenocarcinoma (RR = 2.3, 95% CI 1.4-3.7) and squamous cell carcinoma (RR = 5.2, 95% CI 3.1-8.6) of the esophagus, as well as cardia (RR = 2.1, 95% CI 1.5-3.0) and noncardia stomach (RR = 1.3, 95% CI 1.2-1.6) cancers. We also observed excess risks for esophageal squamous cell carcinoma (RR = 3.5, 95% CI 1.6-7.6) and noncardia stomach cancer (RR = 1.4, 95% CI 1.1-1.9) among snus users who had never smoked. Although confounding by unmeasured exposures, and some differential misclassification of smoking, might have inflated the associations, our study provides suggestive evidence for an independent carcinogenic effect of snus.

Source of inflammatory markers in patients with atrial fibrillation.

AIMS: Elevated levels of C-reactive protein and other inflammatory markers have been reported in some patients with atrial fibrillation (AF). Whether this finding is related to AF per se or to other conditions remains unclear. In addition, the source of inflammatory markers is unknown. Therefore, in the present study, we sought to assess the extent and the source of inflammation in patients with AF and no other concomitant heart or inflammatory conditions. METHODS AND RESULTS: The study group consisted of 29 patients referred for radiofrequency catheter ablation: 10 patients with paroxysmal AF, 8 patients with permanent AF, and 10 control patients with Wolf-Parkinson-White (WPW) syndrome and no evidence of AF (mean age 54 +/- 11 vs. 57 +/- 13 vs. 43 +/- 16). No patient had structural heart diseases or inflammatory conditions. High-sensitive C-reactive protein, interleukin-6 (IL-6), and interleukin-8 (IL-8) were assessed in blood samples from the femoral vein, right atrium, coronary sinus, and the left and right upper pulmonary veins. All samples were collected before ablation. Compared with controls and patients with paroxysmal AF, patients with permanent AF had higher plasma levels of IL-8 in the samples from the femoral vein, right atrium, and coronary sinus, but not in the samples from the pulmonary veins (median values in the femoral vein: 2.58 vs. 2.97 vs. 4.66 pg/mL, P = 0.003; right atrium: 2.30 vs. 3.06 vs. 3.93 pg/mL, P = 0.013; coronary sinus: 2.85 vs. 3.15 vs. 4.07, P = 0.016). A high-degree correlation existed between the IL-8 levels in these samples (correlation coefficient between 0.929 and 0.976, P < 0.05). No differences in the C-reactive protein and IL-6 levels were noted between the three groups of patients. CONCLUSION: The normal levels of C-reactive protein and IL-6, along with the elevated levels of IL-8 in patients with permanent AF but not in those with paroxysmal AF, suggest a link between a low-grade inflammatory reaction and long-lasting AF. The elevated IL-8 levels in the peripheral blood, right atrium, and coronary sinus but not in the pulmonary veins suggest a possible source of inflammation in the systemic circulation.

Heart rate variability is decreased in chronic kidney disease but may improve with hemoglobin normalization.

BACKGROUND: Cardiac autonomic function can be measured by heart rate variability (HRV). Dialysis patients have an abnormally low HRV and are at increased risk for sudden death. A reduction in HRV is associated with anemia. HRV was therefore measured in patients with chronic kidney disease (CKD) after hemoglobin normalization. METHODS: Sixteen nondiabetic patients with CKD stage 4 (glomerular filtration rate 23.7 +/- 13.9 ml/min) and renal anemia received epoetin aiming at a hemoglobin level of 135-150 g/L. HRV was measured by 24-hour Holter electrocardiogram at baseline and after hemoglobin normalization and in a reference group consisting of 16 volunteers without impairment of renal function. RESULTS: Hemoglobin level increased from 100.7 +/- 12.6 g/L to 142.4 +/- 7.2 g/L during the study. At baseline, HRV measured in the time domain as the standard deviation of all normal RR intervals in the entire 24-hour electrocardiogram (SDNN) was 116.3 +/- 39.2 ms compared with 147.5 +/- 27.2 ms in the reference group (p<0.05). The frequency domain measures low-frequency power and total power were 367.7 +/- 350.2 ms2 and 1,368.9 +/- 957.4 ms2 compared with 717.3 +/- 484.5 ms2 and 2,228.3 +/- 1142.4 ms2 (p<0.05) in the reference group. After hemoglobin normalization there was an increase in low-frequency power to 498.3 +/- 432.7 ms2 (p<0.05) and in total power to 1,731.0 +/- 1,069.4 ms2 (p<0.05) while SDNN remained at 120.9 +/- 33.8 ms (p=ns). CONCLUSIONS: CKD patients not yet on dialysis had a reduced HRV, indicating impaired autonomic function, compared with a reference group without impaired renal function. Hemoglobin normalization improved but did not fully normalize HRV. The clinical significance of this deserves further investigation.