Changes in eicosapentaenoic acid and docosahexaenoic acid and risk of cardiovascular events and atrial fibrillation: A secondary analysis of the OMEMI trial.

BACKGROUND: The cardiovascular benefit from n-3 polyunsaturated fatty acids (PUFAs) after acute myocardial infarction (AMI) is controversial, and the importance of serum eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) concentrations for clinical events is unclear. OBJECTIVES: To assess changes in EPA and DHA serum concentrations during n-3 PUFA supplementation and their association with incident cardiovascular events. METHODS: In the OMEMI trial, elderly patients with a recent AMI were randomized to 1.8 g/day of EPA/DHA or control (corn oil) for 2 years. The primary outcome was a composite of AMI, coronary revascularization, stroke, heart failure hospitalization, or all-cause death (major adverse cardiovascular event [MACE]) and the secondary outcome was new-onset atrial fibrillation (AF). RESULTS: EPA and DHA measurements were available in 881 (92% of survivors) participants at randomization and study completion. EPA and DHA increased in the active treatment arm (n = 438) by a median of 87% and 16%, respectively. Greater on-treatment increases in EPA and DHA were associated with decreasing triglycerides, increasing high-density lipoprotein cholesterol, and lower baseline EPA and DHA concentrations. Greater on-treatment increases in EPA were associated with lower risk of MACE (adjusted hazard ratio 0.86 [95% confidence interval, CI, 0.75-0.99], p = 0.034), and higher risk of AF (adjusted hazard ratio (HR) 1.36 [95% CI 1.07-1.72], p = 0.011). Although there were similar tendencies for DHA changes and outcomes, these associations were not statistically significant (HR 0.84 [0.66-1.06] for MACE and 1.39 [0.90-2.13] for AF). CONCLUSION: Greater on-treatment increases in EPA were associated with lower risk of MACE and higher risk of new-onset AF. These data suggest that the cardiovascular effects of increasing n-3 PUFA levels through supplements are complex, involving both potential benefits and harm.

Left ventricular mechanical dispersion in a general population: Data from the Akershus Cardiac Examination 1950 study.

AIMS: Increased left ventricular mechanical dispersion by 2D speckle tracking echocardiography predicts ventricular arrhythmias in ischaemic heart disease and heart failure. However, little is known about mechanical dispersion in the general population. We aimed to study mechanical dispersion in the general population and in diseases associated with increased risk of cardiovascular disease. METHODS AND RESULTS: The present cross-sectional study consists of 2529 subjects born in 1950 included in the Akershus Cardiac Examination (ACE) 1950 study. Global longitudinal strain (GLS) was assessed from 17 strain segments, and mechanical dispersion calculated as the standard deviation of contraction duration of all segments. The cohort was divided according to the median value of mechanical dispersion, and multivariable linear regression models were performed with mechanical dispersion as the dependent variable. The prevalence of coronary artery disease (CAD), hypertension, obesity, and diabetes (P < 0.01 for all) was significantly higher in subjects with supra-median mechanical dispersion. In a multivariable clinical model, CAD (B = 7.05), hypertension (B = 4.15; both P < 0.001), diabetes (B = 3.39), and obesity (B = 1.89; both P < 0.05) were independently associated with increasing mechanical dispersion. When echocardiographic indices were added to the multivariable model, CAD (B = 4.38; P < 0.01) and hypertension (B = 2.86; P < 0.001) remained significant in addition to peak early diastolic tissue velocity e' (B = -2.00), GLS (B = 1.68), and ejection fraction (B = 0.22; P < 0.001 for all). CONCLUSION: In a general middle-aged population, prevalent CAD and hypertension were associated with increasing mechanical dispersion, possibly indicating elevated risk of fatal arrhythmias and sudden cardiac death. Albeit weaker, systolic and diastolic dysfunction, were also associated with increasing mechanical dispersion.

Prevalence of atrial fibrillation and cardiovascular risk factors in a 63-65 years old general population cohort: the Akershus Cardiac Examination (ACE) 1950 Study.

OBJECTIVES: To investigate the sex-specific prevalence of atrial fibrillation (AF), including subclinical AF found by screening in a general population aged 63-65 years. The prevalence of cardiovascular risk factors and their association with AF will also be investigated. DESIGN: Cross-sectional analysis of an observational, prospective, longitudinal, population-based cohort study. SETTING: General population in Akershus county, Norway. PARTICIPANTS: Women and men born in 1950. We included 3706 of 5827 eligible individuals (63.6%); 48.8% were women. METHODS: All participants underwent extensive cardiovascular examinations, including 12-lead ECG. History of AF and other cardiovascular diseases were self-reported. Subsequent validation of all reported or detected AF diagnoses was performed. RESULTS: Mean age was 63.9±0.7 years. Prevalence of ECG-verified AF was 4.5% (women 2.4%, men 6.4%; p<0.001), including screen-detected AF in 0.3% (women 0.1%, men 0.6%; p<0.01). Hypertension was found in 62.0% (women 57.8%, men 66.0%; p<0.001). Overweight or obesity was found in 67.6% (women 59.8%, men 74.9%; p<0.001). By multivariate logistic regression, risk factors associated with AF were height (OR 1.67 per 10 cm; 95% CI 1.26 to 2.22; p<0.001), weight (OR 1.15 per 10 kg; 95% CI 1.01 to 1.30; p=0.03), hypertension (OR 2.49; 95% CI 1.61 to 3.86; p<0.001), heart failure (OR 3.51; 95% CI 1.71 to 7.24; p=0.001), reduced estimated glomerular filtration rate (OR 2.56; 95% CI 1.42 to 4.60; p<0.01) and at least one first-degree relative with AF (OR 2.32; 95% CI 1.63 to 3.31; p<0.001), whereas male sex was not significantly associated (OR 1.00; 95% CI 0.59 to 1.68; p=0.99). CONCLUSION: In this cohort from the general population aged 63-65 years, we found a higher prevalence of known AF than previously reported below the age of 65 years. The additional yield of single time point screening for AF was low. Body size and comorbidity may explain most of the sex difference in AF prevalence at this age. TRIAL REGISTRATION NUMBER: NCT01555411; Results.

High-sensitivity troponin I in persistent atrial fibrillation - relation to NT-proBNP and markers of inflammation and haemostasis.

PURPOSE: 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. METHODS: 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 rs). RESULTS: Baseline levels of hs-TnI correlated significantly, although weakly, with interleukin-6 (rs = 0.260, p = .003), N-terminal pro-B-type natriuretic peptide (rs = 0.251, p = .004), tissue-plasminogen activator antigen (rs = 0.233, p = .008), D-dimer (rs = 0.220, p = .013), E-selectin (rs = 0.207, p = .019), high-sensitivity C-reactive protein (rs = 0.202, p = .022) and vascular cell adhesion molecule-1 (rs = 0.189, p = .032). CONCLUSIONS: Hs-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.

Systematic screening for atrial fibrillation in a 65-year-old population with risk factors for stroke: data from the Akershus Cardiac Examination 1950 study.

Aims: To investigate the yield of screening for atrial fibrillation (AF) in a cohort of 65-year-old individuals from the general population with additional risk factors for stroke. Methods and results: We invited participants with additional risk factors for stroke (CHA2DS2-VASc score ≥2 for men or ≥ 3 for women) without previously known AF from a population-based study in Norway to participate in a 2-week screening for AF. Screening was performed by one-lead 'thumb electrocardiography (ECG)' recordings of 30 s twice daily or when the participants experienced symptoms. In total, 1742 (47.0%) participants of the Akershus Cardiac Examination (ACE) 1950 study had at least one additional risk factor for stroke. Of these, 123 cases reported a history of AF and 101 (5.8%) cases were ECG validated. Eight [0.5%, 95% confidence interval (CI) 0.2-0.9] new AF cases were diagnosed by 12-lead ECG at baseline, and 10 additional participants were diagnosed with AF before screening commenced. We invited all 1601 participants who met the inclusion criteria for screening, of which 1510 (94.3%) participants were included (44% women and 56% men). The screening revealed AF in 13 (0.9%, 95% CI 0.5-1.5) participants. The total prevalence of ECG-validated AF after screening among the 65-year-olds with risk factors for stroke was 7.6% (95% CI 6.4-8.9), in men 10.0% (95% CI 8.2-12.0), and in women 4.3% (95% CI 3.0-6.1) (P < 0.001). Conclusion: In a group of 1510 well-characterized 65-year-olds with risk factors for stroke, 2-week intermittent ECG screening identified undiagnosed AF in 0.9%. The total prevalence of AF was 7.6%.

Effect of sinus rhythm restoration on markers of thrombin generation in atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) confers a hypercoagulable state; however, it is not clear whether restoration of sinus rhythm is associated with normalisation of markers of thrombogenesis. We studied the impact of sustained sinus rhythm on prothrombotic markers, and their predictive abilities in foreseeing rhythm outcome after cardioversion. METHODS: In a double blind, placebo-controlled study, 171 patients referred for electrical cardioversion of persistent AF were randomised to receive candesartan or placebo for 3-6 weeks before and 6 months after cardioversion. Endogenous thrombin potential (ETP), prothrombin fragment 1 + 2 (F1 + 2) and D-dimer were measured before cardioversion and at end of study. These markers were also measured in a reference group comprising 49 subjects without AF. RESULTS: The markers remained unchanged in those 28 patients who maintained sinus rhythm. Discontinuation of warfarin treatment in a subset of 13 low-risk patients in sinus rhythm was associated with significantly higher levels of D-dimer and F1 + 2 compared to the reference group; D-dimer (456 ng/mL (276, 763) vs. 279 ng/mL (192, 348), p = 0.002) and F1 + 2 (700 pmol/L (345, 845) vs. 232 pmol/L (190, 281), p < 0.001). None of the markers were associated with rhythm outcome after electrical cardioversion. CONCLUSIONS: Sustained sinus rhythm for 6 months after cardioversion for AF had no impact on ETP, F1 + 2 or D-dimer levels. Discontinuation of warfarin in low-risk patients with sustained sinus rhythm was associated with significantly higher levels of D-dimer and F1 + 2 compared to the reference group. Our results suggest persistent hypercoagulability in AF patients despite long-term maintenance of sinus rhythm. TRIAL REGISTRATION: The CAPRAF study was registered at clinicaltrials.gov (NCT00130975) in August 2005.

Invasive versus conservative strategy in patients aged 80 years or older with non-ST-elevation myocardial infarction or unstable angina pectoris (After Eighty study): an open-label randomised controlled trial.

BACKGROUND: Non-ST-elevation myocardial infarction (NSTEMI) and unstable angina pectoris are frequent causes of hospital admission in the elderly. However, clinical trials targeting this population are scarce, and these patients are less likely to receive treatment according to guidelines. We aimed to investigate whether this population would benefit from an early invasive strategy versus a conservative strategy. METHODS: In this open-label randomised controlled multicentre trial, patients aged 80 years or older with NSTEMI or unstable angina admitted to 16 hospitals in the South-East Health Region of Norway were randomly assigned to an invasive strategy (including early coronary angiography with immediate assessment for percutaneous coronary intervention, coronary artery bypass graft, and optimum medical treatment) or to a conservative strategy (optimum medical treatment alone). A permuted block randomisation was generated by the Centre for Biostatistics and Epidemiology with stratification on the inclusion hospitals in opaque concealed envelopes, and sealed envelopes with consecutive inclusion numbers were made. The primary outcome was a composite of myocardial infarction, need for urgent revascularisation, stroke, and death and was assessed between Dec 10, 2010, and Nov 18, 2014. An intention-to-treat analysis was used. This study is registered with ClinicalTrials.gov, number NCT01255540. FINDINGS: During a median follow-up of 1·53 years of participants recruited between Dec 10, 2010, and Feb 21, 2014, the primary outcome occurred in 93 (40·6%) of 229 patients assigned to the invasive group and 140 (61·4%) of 228 patients assigned to the conservative group (hazard ratio [HR] 0·53 [95% CI 0·41-0·69], p=0·0001). Five patients dropped out of the invasive group and one from the conservative group. HRs for the four components of the primary composite endpoint were 0·52 (0·35-0·76; p=0·0010) for myocardial infarction, 0·19 (0·07-0·52; p=0·0010) for the need for urgent revascularisation, 0·60 (0·25-1·46; p=0·2650) for stroke, and 0·89 (0·62-1·28; p=0·5340) for death from any cause. The invasive group had four (1·7%) major and 23 (10·0%) minor bleeding complications whereas the conservative group had four (1·8%) major and 16 (7·0%) minor bleeding complications. INTERPRETATION: In patients aged 80 years or more with NSTEMI or unstable angina, an invasive strategy is superior to a conservative strategy in the reduction of composite events. Efficacy of the invasive strategy was diluted with increasing age (after adjustment for creatinine and effect modification). The two strategies did not differ in terms of bleeding complications. FUNDING: Norwegian Health Association (ExtraStiftelsen) and Inger and John Fredriksen Heart Foundation.

High-Sensitivity Troponin I and Rhythm Outcome after Electrical Cardioversion for Persistent Atrial Fibrillation.

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.

Heart and Brain Interactions--the Akershus Cardiac Examination (ACE) 1950 Study Design.

OBJECTIVES: The aim of the Akershus Cardiac Examination (ACE) 1950 Study is to investigate the development and progression of cardiovascular and cerebrovascular disease (CVD/CeVD) in an extensively characterized age cohort of middle-aged subjects with longitudinal long-term follow-up. DESIGN: The ACE 1950 Study is a prospective, population-based, age-cohort study of all men and women born in 1950 in Akershus County, Norway. The study involves a comprehensive baseline examination, especially for CVD/CeVD, including advanced ultrasound imaging and biobanking ("deep phenotyping"). We expect to obtain an inclusion rate of > 60% from the total study population of 5,827 eligible subjects. Enrollment will be completed during 2015. CONCLUSIONS: The ACE 1950 Study will have potential to generate new and relevant insight into identification of subclinical disease progression. Extensive phenotyping will enable identification of novel disease markers and mechanisms for subclinical disease, which can prove important for future disease prevention.

Effects of ω3 supplementation in elderly patients with acute myocardial infarction: design of a prospective randomized placebo controlled study.

BACKGROUND: Both epidemiological and randomized clinical studies suggest that supplementation with very-long-chain marine polyunsaturated n-3 fatty acids (n-3 PUFA) have cardioprotective effects, however these results are not without controversy. Study population, sample-size, type of supplementation and type of endpoint have all varied widely accross different studies.Therefore, the aims of the present study are to evaluate the effect of 2 years supplementation with capsules of very-long chain marine n-3 PUFA on top of standard therapy in elderly patients after acute myocardial infarction (AMI).In addition, special characteristics of this population with regard to prediction of clinical outcome will be investigated. The hypothesis is that this supplementation on top of modern therapy will reduce the occurence of major cardiovascular events (MACE). We present the design of the OMEMI (OMega-3 fatty acids in Elderly patients with Myocardial Infarction) study. METHODS/DESIGN: The OMEMI study is designed as a randomized, placebo-controlled double-blind multicenter trial.Included are patients ≥70-82 years of age who have sustained AMI. Patients of either gender are eligible. Sample size calculation based on existing literature has resulted in the need for 1400 patients followed for 2 years, based on the assumption that the n-3 PUFA supplementation will reduce MACE with 30%. The study medication is Pikasol® Axellus AS, Norway, 3 capsules (1.8 g eicosapentaenoic acid (EPA) + docohexaenoic acid (DHA)) per day, and matching placebo is corn oil. The Primary end-point is the composite of total mortality, first non-fatal recurring AMI, stroke and revascularization. Secondary end-point is the occurrence of new onset atrial fibrillation. Extensive biobanking will be performed, including adipose tissue biopsies. Compliance will be assessed by measurements of the fatty acid profile in serum, sampled at inclusion, after 12 months and at the end of study. DISCUSSION: The OMEMI study is scheduled to terminate when the last included patient has been followed for 2 years. To the best of our knowledge, the OMEMI study is the first to evaluate the effect of n-3 PUFAs on CVDs and mortality in a high risk elderly population having suffered an acute myocardial infarction. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01841944.

Angiotensin II blockade, YKL-40 and maintenance of sinus rhythm after electrical cardioversion for atrial fibrillation.

High levels of the novel inflammatory marker YKL-40 have been demonstrated in inflammatory environments and in remodeling of the extracellular matrix. Both are key components in atrial wall remodeling in atrial fibrillation (AF). We studied the relation between rhythm outcome after electrical cardioversion (ECV) for persistent AF and serum levels of YKL-40. A secondary point of interest was a potential effect of the angiotensin receptor blocker candesartan on YKL-40 levels. In the Candesartan in the Prevention of Relapsing Atrial Fibrillation (CAPRAF) study, 171 patients with persistent AF were randomized to receive candesartan 8mg once daily or placebo for 3-6 weeks before ECV and candesartan 16mg once daily or placebo for 6 months after ECV. Serum levels of YKL-40 were measured in fasting blood samples collected at baseline and at end of the study. Mean age was 64±11 years, and 39 (22.8%) were women. Sinus rhythm was maintained for 6 months after ECV in 41 (23.9%). Baseline levels of YKL-40 were significantly correlated to age (Spearmans rho; rs=0.442; p<0.001), CHA2DS2-VASc(1) score (rs=0.256; p<0.001) and left atrial diameter (rs=0.185; p=0.017). By use of Kaplan-Meier quartile analysis of baseline YKL-40 levels, no relation between YKL-40 levels and risk of AF recurrence was found. End of study YKL-40 levels were unchanged from baseline, both in patients with AF recurrence and those maintaining sinus rhythm for 6 months. Treatment with candesartan had no influence on serum YKL-40 levels.

The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study.

BACKGROUND: During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. METHODS AND RESULTS: Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE-eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69-1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04-1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80-1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. CONCLUSIONS: During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death.

Mortality and recurrence after treatment of VTE: long term follow-up of patients with good life-expectancy.

INTRODUCTION: After completed anticoagulant treatment for acute VTE, both the subsequent mortality and risk of recurrent VTE are high, probably related to the frequent presence of serious disease in these patients. The aim of the study was to determine survival and recurrence in selected patients with good life-expectancy, and to evaluate risk factors. METHODS: The 323 patients were followed for median 7.4 years (range 4.1-11.9) after cessation of anticoagulation. Survival analysis and Cox-regression were used for univariate and multivariate analysis. RESULTS: The cumulative incidence of survival after 5 years was 93.4%. Standardised mortality ratio was 1.42 for men and 1.28 for women. Patients without a transient risk factor prior to the index VTE were associated with higher risk of mortality compared to risk of mortality in patients with a transient risk factor (hazard ratio (HR) 2.81; 95% CI 1.40-5.62). Recurrence of VTE after 5 years was 19.0%. A persistent risk factor or a spontaneous VTE was associated with higher risk of recurrence compared to a transient risk factor (HR 2.39; 95% CI 1.44-3.95). Elevated D-dimer levels increased the risk, and immobilisation prior to the index VTE reduced the risk of recurrence. Sex, age and thrombophilia were not independent risk factors for recurrence. CONCLUSIONS: Despite a low mortality rate in this selected cohort, the recurrence rate and risk factors for recurrence were similar to findings reported in unselected populations. VTE unrelated to a transient risk factor was associated with increased mortality compared to mortality in patients with a transient risk factor.

L-arginine, asymmetric dimethylarginine and rhythm outcome after electrical cardioversion for atrial fibrillation.

OBJECTIVES: It was our aim to study the levels of L-arginine, the substrate for nitric oxide and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, and their relation to the maintenance of sinus rhythm after electrical cardioversion for atrial fibrillation (AF), as well as the effects of angiotensin receptor blockade on these variables. METHODS: In a double-blind, placebo-controlled study, patients with persistent AF were randomised to receive candesartan 8 mg once daily or placebo for 3-6 weeks before and candesartan 16 mg once daily or placebo for 6 months after cardioversion. As part of this study, plasma levels of L-arginine and ADMA were measured at baseline and at the end of the study. RESULTS: Baseline levels of L-arginine, ADMA and the L-arginine/ADMA ratio were not predictive of rhythm outcome, and their levels were not influenced by treatment with candesartan. However, the L-arginine/ADMA ratio increased in patients who remained in sinus rhythm (n = 37) for 6 months when compared with patients with AF recurrence (n = 61; p = 0.008). CONCLUSION: Neither L-arginine nor ADMA or their ratio were predictive of rhythm outcome after cardioversion, and they were not influenced by treatment with candesartan. However, the L-arginine/ADMA ratio increased in patients still in sinus rhythm 6 months after cardioversion.

Effects of angiotensin receptor blockade on serial P-wave signal-averaged electrocardiograms after electrical cardioversion of persistent atrial fibrillation.

AIMS: To evaluate the effects of the angiotensin II type 1 receptor blocker candesartan on P-wave signal-averaged electrocardiogram (P-SAECG) after electrical cardioversion in patients with atrial fibrillation (AF). METHODS AND RESULTS: One hundred and seventy-one patients with persistent AF were randomized to receive candesartan 8 mg/day or placebo for 3-6 weeks before and candesartan 16 mg/day or placebo for 6 months after electrical cardioversion. P-SAECG was recorded in 114 patients (57 in each treatment group) after cardioversion and repeated in those with sinus rhythm at 1 and 6 weeks, and 3 and 6 months. Filtered P-wave duration (FPD), root-mean-squared (RMS) voltages of the terminal 40 ms of the filtered P-wave, RMS voltage of the entire filtered P-wave, and the integral of the voltages in the entire PD were analysed. No effects of candesartan were observed on any P-SAECG parameter at baseline. In the subgroup of patients in sinus rhythm after 6 months, FPD was significantly shorter both at baseline (151 +/- 16 vs. 163 +/- 16 ms) and at 6 months (143 +/- 12 vs. 153 +/- 15 ms) in the candesartan (n = 15) compared with the placebo group (n = 21). CONCLUSION: Treatment with candesartan was associated with a shorter FPD in patients remaining in sinus rhythm for 6 months.

Determinants of cardiac troponin T elevation in COPD exacerbation - a cross-sectional study.

BACKGROUND: Cardiac Troponin T (cTnT) elevation during exacerbations of chronic obstructive pulmonary disease (COPD) is associated with increased mortality the first year after hospital discharge. The factors associated with cTnT elevation in COPD are not known. METHODS: From our hospital's database, all patients admitted with COPD exacerbation in 2000-03 were identified. 441 had measurement of cTnT performed. Levels of cTnT > or = 0.04 microg/l were considered elevated. Clinical and historical data were retrieved from patient records, hospital and laboratory databases. Odds ratios for cTnT elevation were calculated using logistic regression. RESULTS: 120 patients (27%) had elevated cTnT levels. The covariates independently associated with elevated cTnT were increasing neutrophil count, creatinine concentration, heart rate and Cardiac Infarction Injury Score (CIIS), and decreasing hemoglobin concentration. The adjusted odds ratios (95% confidence intervals in parentheses) for cTnT elevation were 1.52 (1.20-1.94) for a 5 x 106/ml increase in neutrophils, 1.21 (1.12-1.32) for a 10 micromol/l increase in creatinine, 0.80 (0.69-0.92) for a 1 mg/dl increase in hemoglobin, 1.24 (1.09-1.42) for a 10 beats/minute increase in heart rate and 1.44 (1.15-1.82) for a 10 point increase in CIIS. CONCLUSION: Multiple factors are associated with cTnT elevation, probably reflecting the wide panorama of comorbid conditions typically seen in COPD. The positive association between neutrophils and cTnT elevation is compatible with the concept that an exaggerated inflammatory response in COPD exacerbation may predispose for myocardial injury.

Candesartan, NT-proBNP and recurrence of atrial fibrillation after electrical cardioversion.

BACKGROUND: Some small studies have suggested that low levels of brain natriuretic peptide (BNP) measured before electrical cardioversion for atrial fibrillation (AF) may be associated with maintenance of sinus rhythm after the procedure. We hypothesized that 1) plasma levels of N-terminal fragment of proBNP (NT-proBNP) measured before cardioversion were predictive of AF recurrence, 2) treatment with candesartan would influence the levels of NT-proBNP, and 3) restoration of sinus rhythm would reduce the levels of NT-proBNP. METHODS: We investigated 171 patients with persistent AF who underwent electrical cardioversion in a prospective, blinded, placebo-controlled clinical trial (Candesartan in the Prevention of Relapsing Atrial Fibrillation, CAPRAF). Plasma levels of NT-proBNP were measured at baseline and at the end of the study. Patients with congestive heart failure were excluded from the study. RESULTS: Baseline NT-proBNP levels were similar in patients with unsuccessful cardioversion (n=22), patients with successful cardioversion remaining in sinus rhythm (n=40) and patients with successful cardioversion who had a relapse of AF (n=89): median (interquartile range) 73.9 pmol/L (43.2, 145.6); 88.2 pmol/L (59.2, 147.5) and 90.0 pmol/L (55.3, 138.4), respectively. Maintenance of sinus rhythm was associated with a significant reduction in NT-proBNP levels, whereas NT-proBNP levels were not affected by treatment with candesartan. CONCLUSIONS: Plasma NT-proBNP concentration measured before electrical cardioversion did neither predict cardioversion success nor relapse of AF in patients without heart failure. Treatment with candesartan did not affect the levels of NT-proBNP. Maintained sinus rhythm during follow-up was associated with a significant reduction in NT-proBNP levels.

Fibrillatory rate response to candesartan in persistent atrial fibrillation.

INTRODUCTION: Angiotensin-receptor blockers may exert favourable anti-arrhythmic effects in atrial fibrillation (AF), but their mechanisms are not fully understood. In this study, we tested the hypotheses that (i) candesartan reduces atrial fibrillatory rate and (ii) fibrillatory rate and its response to candesartan are related with the outcome of cardioversion. For this purpose, a post hoc subanalysis of the randomized, placebo-controlled CAPRAF (Candesartan in the Prevention of Relapsing Atrial Fibrillation) trial was performed. METHODS AND RESULTS: Patients with AF undergoing electrical cardioversion were randomized to receive candesartan 8 mg once daily (n = 58) or matching placebo (n = 66) and no additional class I or III anti-arrhythmic drugs. Fibrillatory rate was determined from ECG lead V1 at baseline and at the day of cardioversion using spatiotemporal QRST cancellation and time-frequency analysis. The median time on treatment was 29 days. Candesartan reduced fibrillatory rate [399 +/- 48 vs. 388 +/- 49 fibrillations/min (fpm), P = 0.04], but not placebo (402 +/- 58 vs. 402 +/- 61 fpm, P = 0.986). Candesartan effects were only observed if the baseline fibrillatory rate was high [>420 fpm: 445 +/- 21 vs. 415 +/- 49 fpm, P = 0.006 vs. intermediate (360-420 fpm): 397 +/- 19 vs. 391 +/- 37 fpm, P = 0.351 vs. low (<360 fpm): 326 +/- 26 vs. 338 +/- 29 fpm, P = 0.179]. Cardioversion success was 100% in patients with an on-treatment rate <360 fpm vs. 83% in patients with higher rates (P = 0.02). Risk for AF recurrence was similar in patients with low (64%), intermediate (75%), or high on-treatment rates (63%, P = 0.446) and was also independent of candesartan effects on the fibrillatory rate. CONCLUSION: In patients with persistent AF, candesartan decreases the fibrillatory rate, but this effect is restricted to patients with high baseline fibrillatory rates and is not associated with improved cardioversion outcome. Fibrillatory rates <360 fpm are associated with successful cardioversion, but not with AF recurrence.

Underdiagnosis of myocardial infarction in COPD - Cardiac Infarction Injury Score (CIIS) in patients hospitalised for COPD exacerbation.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are usually former or current smokers, and are at increased risk of ischemic heart disease. We used Cardiac Infarction Injury Score (CIIS) to assess the prevalence of prior myocardical infarction (MI) in COPD patients and compared this to clinicians' previous diagnosis of MI. METHODS: From the hospital database, 897 patients (mean age 70.9 years, 50.8% female) discharged after treatment for COPD exacerbation in the years 2000-2003 were identified. Disease history was established from medical records and the hospital patient database. Electrocardiograms from the day of admission were available in 827 patients, and were coded according to the CIIS algorithm by an investigator blinded to clinical and outcome data. The CIIS score was validated using follow-up data for the first year after discharge. RESULTS: Two hundred and twenty-nine patients had CIIS > or = 20, out of whom only 30% (95% confidence interval: 24-36%, n=68) had a recognised history of MI. Female patients had a lower probability of diagnosis despite ECG evidence. Validation of CIIS using multivariate Cox regression analysis showed that a score > or = 20 had independent prognostic value for the first year after discharge, with an adjusted HR of 1.52 (1.14-2.03). CONCLUSION: Unrecognised MI is common in patients hospitalised with COPD exacerbation. Less than one-third of patients with ECG evidence of previous MI by the CIIS system actually have the diagnosis in their medical records.