Vernakalant for Rapid Cardioversion of Recent-Onset Atrial Fibrillation: Results from the SPECTRUM Study.

AIMS: Rapid restoration of sinus rhythm using pharmacological cardioversion is commonly indicated in patients with symptomatic recent-onset atrial fibrillation (AF). The objectives of this large, international, multicenter observational study were to determine the safety and effectiveness of intravenous (IV) vernakalant for conversion of AF to sinus rhythm in daily practice. METHODS AND RESULTS: Consenting patients with symptomatic recent-onset AF (< 7 days) treated with IV vernakalant were enrolled and followed up to 24 h after the last infusion or until discharge, in order to determine the incidence of predefined serious adverse events (SAEs) and other observed SAEs and evaluate the conversion rate within the first 90 min. Overall, 2009 treatment episodes in 1778 patients were analyzed. The age of patients was 62.3 ± 13.0 years (mean ± standard deviation). Median AF duration before treatment was 11.1 h (IQR 5.4-27.0 h). A total of 28 SAEs occurred in 26 patients including 19 predefined SAEs, i.e., sinus arrest (n = 4, 0.2%), significant bradycardia (n = 11, 0.5%), significant hypotension (n = 2, 0.1%), and atrial flutter with 1:1 conduction (n = 2, 0.1%). There were no cases of sustained ventricular arrhythmias or deaths. All patients who experienced SAEs recovered fully (n = 25) or with sequelae (n = 1). Conversion rate to sinus rhythm was 70.2%, within a median of 12 min (IQR 8.0-28.0 min). CONCLUSIONS: This large multicenter, international observational study confirms the good safety profile and the high effectiveness of vernakalant for the rapid cardioversion of recent-onset AF in daily hospital practice.

ST segment depression on 24-hour electrocardiography predicts incident atrial fibrillation in two population-based cohorts.

Aims: ST-depression at 24hECG has not been studied in relation to atrial fibrillation (AF) risk. We aimed to determine whether ST-depression at 24hECG was associated with incident AF in two Swedish population-based cohorts - a sub-cohort of the Malmö Diet and Cancer study (MDCS), and the cohort 'Men born in 1914', and to determine whether 24hECG could be used to predict AF development. Methods and results: There were 378 acceptable 24hECG recordings in the MDCS (mean age 64.5 years, 43% men) and 394 acceptable recordings in 'Men born in 1914' (mean age 68.8 years). Incidence of AF was monitored using national registers of hospitalizations and outpatient visits in Sweden. Mean follow-up ± SD (cumulative incidence) was 10.4 ± 2 years (11.3%) in MDCS, and 10.9 ± 4 years (7.3%) in 'Men born in 1914'. ST-depressions were independently associated with incident AF; hazard ratio (HR) (95% CI) 2.41 (1.29-4.50, P = 0.006) and 2.28 (1.05-4.95, P = 0.038) after adjustment [age, sex, height, weight, systolic blood pressure, smoking, anti-hypertensive drugs, LDL/total cholesterol, and HOMA-IR (in MDCS)]. AF incidence was substantially lower in individuals who had neither ST-depressions or high supraventricular activity (SVA, negative predictive value 0.97 and 0.94, in MDCS and 'Men born in 1914', respectively), and similar in men and women. Conclusion: ST-depression at 24h-ECG is independently associated with incident AF, and incidence is substantially lower in individuals with neither ST-depression or high SVA. 24hECG can be used not only to diagnose AF but also to identify individuals at high and low AF risk.

Is one month treatment with dabigatran before cardioversion of atrial fibrillation sufficient to prevent thromboembolism?

AIMS: The use of direct oral anticoagulants (DOACs) in patients undergoing elective direct current (DC) cardioversion of non-acute atrial fibrillation (AF) can potentially shorten the time from initiation of anticoagulation treatment to cardioversion, compared with warfarin. The safety of this strategy needs to be investigated. Data from subgroup analysis from clinical trials with DOAC do not clarify whether 4-week treatment with DOAC is sufficient to prevent thromboembolism (TE) after cardioversion. The aim of this retrospective study was to assess the incidence of TE in anticoagulant naive patients converted after one month's pre-treatment with dabigatran. METHODS AND RESULTS: We scrutinized the medical records of 631 patients where dabigatran had been used prior to elective DC cardioversion. Transoesophageal echocardiography was rarely performed. Thromboembolism within 30 days of cardioversion was the primary endpoint. A total of 570 patients were naive to OAC when dabigatran was initiated. The mean age in this group was 64.2 ± 11 years and 31.7% were women. The mean CHA2DS2-VASc score was 2.0 ± 1.5. The dose of dabigatran was 150 mg b.i.d. in 94% of the patients. The median time from initiation of dabigatran to cardioversion was 32.0 ± 15 days. In 91% cardioversion resulted in sinus rhythm. During the 30-day follow-up, three TE occurred for an incidence of 0.53% (0.18-1.54). CONCLUSION: In this retrospective study from clinical material, we found a low incidence of TE when dabigatran was used as TE prophylaxis in association with elective cardioversion. These results indicate that dabigatran is a safe alternative strategy to warfarin during cardioversion in patients with AF.

Predictors of successful cardioversion with vernakalant in patients with recent-onset atrial fibrillation.

BACKGROUND: Vernakalant is a novel atrial-selective antiarrhythmic drug able to convert recent-onset atrial fibrillation (AF) with reportedly low proarrhythmic risk. Successful cardioversion predictors are largely unknown. We sought to evaluate clinical and electrocardiographic predictors of cardioversion of recent-onset AF with vernakalant. METHODS: Consecutive patients with AF ≤48 hours admitted for cardioversion with vernakalant (n = 113, median age 62 years, 69 male) were included. Sinus rhythm (SR) within 90 minutes after infusion start was considered to be successful cardioversion. Predictive values of demographics, concomitant therapy, comorbidities, and electrocardiographic parameters were assessed. Atrial fibrillatory rate (AFR), exponential decay, and mean fibrillatory wave amplitude were measured from surface ECG using QRST cancellation and time-frequency analysis. RESULTS: Cardioversion was achieved in 66% of patients. Conversion rate was higher in women than in men (80% vs 58%, P = 0.02) while none of other clinical characteristics, including index AF episode duration, could predict SR restoration. Female gender was predictive of vernakalant's effect in logistic regression analysis (OR = 2.82 95%CI 1.18-6.76, P = 0.020). There was no difference in AFR (350 ± 60 vs 348 ± 62 fibrillations per minute [fpm], P = 0.893), mean fibrillatory wave amplitude (86 ± 33 vs 88 ± 67 µV, P = 0.852), or exponential decay (1.30 ± 0.42 vs 1.35 ± 0.42, P = 0.376) between responders and nonresponders. CONCLUSIONS: Female gender is associated with a higher rate of SR restoration using intravenous (i.v.) vernakalant for recent-onset AF. ECG-derived indices of AF organization, which previous studies associated with effect of rhythm control interventions, did not predict vernakalant's effect.

Reduced forced expiratory volume is associated with increased incidence of atrial fibrillation: the Malmo Preventive Project.

AIMS: Reduced forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) have been associated with increased incidence of cardiovascular diseases. However, whether reduced lung function is also a risk factor for incidence of atrial fibrillation (AF) is still unclear. We aimed to determine whether lung function predicted AF in the Malmö Preventive Project, a large population-based cohort with a long follow-up. METHODS AND RESULTS: The study population consisted of 7674 women and 21 070 men, mean age 44.6 years. The cohort was followed on average for 24.8 years, during which time 2669 patients were hospitalized due to AF. The incidence of AF in relationship to quartiles of FEV1 and FVC and per litre decrease at baseline was determined using a Cox proportional hazards model adjusted for age, height, weight, current smoking status, systolic blood pressure, erythrocyte sedimentation rate, and fasting blood glucose. Forced expiratory volume in one second was inversely related to incidence of AF (per litre reduction in FEV1) hazard ratio (HR): 1.39 [95% confidence interval (CI): 1.16-1.68; P = 0.001] for women, and HR: 1.20 (95% CI: 1.13-1.29; P < 0.0001) for men. Forced vital capacity was also inversely related to incidence of AF (per litre reduction in FVC) HR: 1.20 (95% CI: 1.03-1.41; P = 0.020) for women, and HR: 1.08 (95% CI: 1.02-1.14; P = 0.01) for men. This relationship was consistent in non-smokers as well as smokers, and among individuals younger than the median age of 45.8 years or normotensive subjects. CONCLUSION: Impaired lung function is an independent predictor of AF. This may explain some risk of AF that is currently unaccounted for.

Low fasting plasma insulin is associated atrial fibrillation in men from a cohort study--the Malmö preventive project.

BACKGROUND: Type 2 diabetes has been associated with increased incidence of atrial fibrillation (AF) and cardiovascular disease. Controversy remains regarding the role of insulin in the epidemiology of AF risk. The aim of the present study was to study the association between fasting plasma insulin (FPI) and incidence of AF, as well as any effect modification by fasting blood glucose (FBG) or 2 h post-load blood glucose and body mass index (BMI). METHODS: The study population consisted of 6052 men and 1014 women followed for an average of 26.2 years. There were 983 cases of incident AF. Analysis was performed using Cox regression and competing risks regression approaches. The population was analysed as a whole, and by subgroups according to glucose levels and BMI. RESULTS: After adjustment for age, height, weight, systolic blood pressure and smoking there was a significant inverse association between FPI and AF (hazard ratio; HR) for 4th vs. 1st quartile: 0.69 (95% confidence interval (CI): 0.57-0.83, p < 0.0001) in the cohort as a whole. Among men the corresponding values were HR 0.64 (95% CI 0.52-0.78, p < 0.001) and among women HR 1.16 (95% CI 0.69-1.93, p = 0.58); p-value for interaction 0.06. The protective effects of insulin tended to be weaker in subjects with elevated fasting glucose, implying that the relation between FPI and incident AF could be dependent on the status of individual's glucose metabolism. CONCLUSIONS: High levels of FPI are associated with lower risk of incident AF in a middle-aged population with a long follow-up.

Data standards for atrial fibrillation/flutter and catheter ablation: the European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart).

AIMS: Standardized data definitions are essential for monitoring and assessment of care and outcomes in observational studies and randomized controlled trials (RCTs). The European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart) project of the European Society of Cardiology aimed to develop contemporary data standards for atrial fibrillation/flutter (AF/AFL) and catheter ablation. METHODS AND RESULTS: We used the EuroHeart methodology for the development of data standards and formed a Working Group comprising 23 experts in AF/AFL and catheter ablation registries, as well as representatives from the European Heart Rhythm Association and EuroHeart. We conducted a systematic literature review of AF/AFL and catheter ablation registries and data standard documents to generate candidate variables. We used a modified Delphi method to reach a consensus on a final variable set. For each variable, the Working Group developed permissible values and definitions, and agreed as to whether the variable was mandatory (Level 1) or additional (Level 2). In total, 70 Level 1 and 92 Level 2 variables were selected and reviewed by a wider Reference Group of 42 experts from 24 countries. The Level 1 variables were implemented into the EuroHeart IT platform as the basis for continuous registration of individual patient data. CONCLUSION: By means of a structured process and working with international stakeholders, harmonized data standards for AF/AFL and catheter ablation for AF/AFL were developed. In the context of the EuroHeart project, this will facilitate country-level quality of care improvement, international observational research, registry-based RCTs, and post-marketing surveillance of devices and pharmacotherapies.

Aortic stenosis and mitral regurgitation as predictors of atrial fibrillation during 11 years of follow-up.

BACKGROUND: There is limited information about any association between the onset of atrial fibrillation (AF) and the presence of valvular disease. METHODS: We retrospectively examined 940 patients in sinus rhythm, examined by echocardiography in 1996. During 11 years of follow-up, we assessed the incidence of AF and outcome defined as valvular surgery or death, in relation to baseline valvular function. AS (aortic stenosis) severity at baseline examination was assessed using peak transaortic valve pressure gradient. RESULTS: In univariate analysis, the risk of developing AF was related to AS (significant AS versus no significant AS; hazard ratio (HR) 3.73, 95% confidence interval (CI) 2.39-5.61, p<0.0001) and mitral regurgitation (MR) (significant MR versus no significant MR; HR 2.52, 95% CI 1.77-3.51, p<0.0001). Also the risk of valvular surgery or death was related to AS (HR 3.90, 95% CI 3.09-4.88, p<0.0001) and MR (HR 2.07, 95% CI 1.67-2.53, p<0.0001). In multivariate analyses, adjusting for sex, age, other valvular abnormalities, left ventricular ejection fraction and left atrial size - AS was independently related to both endpoints, whereas MR was not independently related to either endpoint. CONCLUSIONS: AS, but not MR, was independently predictive of development of AF and combined valvular surgery or death. In patients with combined AS and MR, the grade of AS, more than the grade of MR, determined the risk of AF and combination of valvular surgery or death. Further studies using contemporary echocardiographic quantification of aortic stenosis are warranted to confirm these retrospective data based on peak transaortic valve pressure gradient.

Elevated premature ventricular complex counts on 24-hour electrocardiogram predict incident atrial fibrillation and heart failure-A prospective population-based cohort study.

Background: Premature ventricular complexes (PVCs) are known to predict heart failure (HF) and premature atrial contractions (PACs) are known to predict atrial fibrillation (AF) and stroke. PVCs and PACs share pathophysiological mechanisms; however, the combined effects of PVCs and PACs on HF, AF, and stroke risk have not been studied. Objectives: To study elevated PVC counts on 24-hour electrocardiogram monitoring (24hECG) in relation to incidence of AF, HF, and stroke, and whether this effect is altered by PAC frequency. Methods: The prospective population-based Malmö Diet and Cancer study includes 24hECG registrations in 375 AF- and HF-free subjects (mean age 65 years, 55% women). During 17 years of follow-up there were 28 HF, 89 AF, and 28 stroke events. The hazard ratios (HR) of elevated PVC counts (defined as the top quartile, ≥77/24 hours) vs lower quartiles were assessed using multivariable adjusted Cox regression models. Results: Elevated PVC counts predicted incident AF (HR 1.9, 95% confidence interval [CI] 1.2-3.0) and HF (HR 3.1, 95% CI 1.4-7.0). Results were similar after adjustment for NT-proBNP and PACs. Multiform PVCs were associated with even higher risks (HR 2.8, 95% CI: 1.7-4.6 for AF; HR 5.0, 95% CI 2.2-11.7 for HF), as was the presence of both elevated PACs and PVCs (9% of the population, HR 4.1, 95% CI 2.4-6.8 for AF and HR 4.3, 95% CI 1.7-11.4 for HF). No significant association was found between elevated PVC counts and incident stroke. Conclusion: Elevated PVC counts predict incident AF and HF, particularly if PVCs are multiform or occur in combination with elevated PAC counts.

Risk prediction of future cardiac arrest by evaluation of a genetic risk score alone and in combination with traditional risk factors.

OBJECTIVES: Coronary heart disease (CHD) is a leading cause of death globally, commonly through sudden cardiac death. Cardiac arrest of cardiac origin (CA) is associated with a poor prognosis and there is a great need for risk assessment and intensified preventive actions. In this study we aim to assess if a genetic risk score for CHD, composed of 50 common CHD susceptibility variants (GRS), predicts CA and to evaluate a novel composite risk score including traditional risk factors as well as GRS. METHODS: The GRS score alone and in combination with traditional CHD risk factors were examined in relation to CA incidence among 23 000 middle aged subjects during 18.9 years of follow-up. The cohort excluded patients with a diagnosed history of CHD, heart failure or stroke. RESULTS: Two-hundred-fifty-two patients suffered a cardiac arrest during the follow up, of which 181 were CA. In a multivariate model with CHD risk factors, high versus low genetic risk predicted CA with a hazard ratio (HR) of 2.49 {(95% CI 1.50-4.12) (P < 0.001)}, surpassed only by higher estimates for male sex {HR = 2.91 (95% CI 2.09-4.06) (P < 0.001)}, ages 50-65 {HR = 2.74 (95% CI 1.42-5.25) (P = 0.003)} and ages 65-74 {HR = 5.10 (95% CI 2.56-10.16) (P < 0.001)}. Smoking, dyslipidemia, hypertension and diabetes mellitus also predicted CA but with lower HRs than GRS. A novel composite risk score including CHD risk factors as well as GRS predicted CA with a HR = 110.81 {(95% CI 15.43-795.63) (P < 0.001)} for the highest (5) versus the lowest quintile (1) of the risk score. CONCLUSIONS: Genetic risk of CHD is strongly associated with incident CA and when combined with traditional CHD risk factors may identify individuals who benefit from intensified preventive pharmacological treatment.

Renal effects of aspirin are clearly dose-dependent and are of clinical importance from a dose of 160 mg.

BACKGROUND: High doses of aspirin counteract the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors. It is not known how low-dose aspirin, with concomitant ACE-inhibitor treatment, affects renal function. AIM: To study renal effects of different doses of aspirin in elderly healthy volunteers who had an activated renin-angiotensin system. METHODS: Sixteen subjects each received two different doses of aspirin (0 and160 mg or 80 and 320 mg) after pre-treatment with bendroflumethiazide and enalapril, in a randomised double-blind, cross-over fashion. RESULTS: Least square means of the observations 30 to 180 min after dosing, showed that urine flow, GFR, excretion rates of sodium, osmolality clearance and free water clearance were significantly decreased in a dose-dependent manner. Urine flow, sodium excretion rate and free water clearance were significantly lower with 320 mg aspirin vs. 0 mg and 80 mg, and GFR was significantly lower with 320 mg vs. 80 mg. Urine flow, sodium excretion rate, free water and osmolality clearance was significantly lower with aspirin 160 mg vs. 0 mg. CONCLUSION: The dose-dependent renal effects of aspirin are of clinical importance from a dose of 160 mg. The adverse influence of aspirin doses higher than 80 mg should be taken into consideration in patients with heart failure.

Irregularity and lack of p waves in short tachycardia episodes predict atrial fibrillation and ischemic stroke.

BACKGROUND: Atrial fibrillation (AF) is defined as an irregular supraventricular tachycardia (SVT) without p waves, with duration >30 seconds. Whether AF characteristics during short SVT episodes predict AF and stroke is not known. OBJECTIVE: The purpose of this study was to determine whether irregularity and lack of p waves, alone or in combination, during short SVT episodes increase the risk of incident AF and ischemic stroke. METHODS: The population-based Malmö Diet and Cancer study includes 24-hour ECG screening of 377 AF-free individuals (mean age 64.5 years; 43% men) who were prospectively followed for >13 years. There were 65 AF events and 25 ischemic stroke events during follow-up. Subjects with an SVT episode ≥5 beats were identified, and the longest SVT episode was assessed for irregularity and lack of p waves. The association between SVT classification and AF and stroke was assessed using multivariable adjusted Cox regression. RESULTS: The incidence of AF increased with increasing abnormality of the SVTs. The risk-factor adjusted hazard ratio for AF was 4.95 (95% confidence interval 2.06-11.9; P <.0001) for those with short irregular SVTs (<70 beats) without p waves. The incidence of ischemic stroke was highest in the group with regular SVT episodes without p waves (hazard ratio 14.2; 95% confidence interval 3.76-57.6; P <.0001, adjusted for age and sex). CONCLUSION: Characteristics of short SVT episodes detected at 24-hour ECG screening are associated with incident AF and ischemic stroke. Short irregular SVTs without p waves likely represent early stages of AF or atrial myopathy. Twenty-four-hour ECG could identify subjects suitable for primary prevention efforts.

Treatments with losartan or enalapril are equally sensitive to deterioration in renal function from cyclooxygenase inhibition.

BACKGROUND: The beneficial effects of angiotensin converting enzyme (ACE)-inhibitors are in part mediated through the inhibition of the degradation of the vasodilator bradykinin. The bradykinin effect is counteracted by cyclooxygenase-inhibitors. Angiotensin receptor blockers (ARBs) do not affect bradykinin. AIMS: To test the hypothesis that renal counteraction from a cyclooxygenase-inhibitor, diclofenac, is different in subjects treated with an ACE-inhibitor, enalapril compared with an ARB, losartan. METHODS: Twelve elderly, healthy, slightly over-hydrated subjects received diclofenac orally after pre-treatment with a diuretic, bendroflumethiazide, and enalapril or bendroflumethiazide and losartan, in a double-blind cross-over fashion, with a wash-out period of at least 1 week. RESULTS: Diclofenac reduced GFR significantly from 81(64-98) ml/min at first observations after dose for enalapril to 29(16-42) and from 76(64-88) after losartan to 35(24-46). There was no significant difference between enalapril and losartan in GFR. Diclofenac induced decreases in urine flow, excretion rates and clearances of sodium, osmolality clearance and free water clearance, irrespective of treatment with enalapril or losartan. However, serum potassium and handling of potassium were significantly lower after losartan-treatment. CONCLUSION: The negative renal effects of diclofenac administration in subjects with activation of the renin-angiotensin system and enalapril treatment are the same in subjects with activation of the renin-angiotensin system and losartan treatment.

Midlife risk factor exposure and incidence of cardiac arrest depending on cardiac or non-cardiac origin.

OBJECTIVE: Little is known about midlife risk factors of future cardiac arrest. Our objective was to evaluate cardiovascular risk factors in midlife in relation to the risk of cardiac arrest (CA) of cardiac and non-cardiac origin later in life. METHODS: We cross-matched individuals of the population based Malmö Diet and Cancer study (n=30,447) with the local CA registry of the city of Malmö. Baseline exposures were related to incident CA. RESULTS: During a mean follow-up of 17.6±4.6years, 378 CA occurred, of whom 17.2% survived to discharge. Independent midlife risk factors for CA of cardiac origin included coronary artery disease {HR 2.84 (1.86-4.34) (p<0.001)}, diabetes mellitus {HR 2.37 (1.61-3.51) (p<0.001)} and smoking {HR 1.95 (1.49-2.55) (p<0.001)}. Dyslipidemia and history of stroke were also significantly associated with an elevated risk for CA of cardiac origin. Independent midlife risk factors for CA of non-cardiac origin included obesity (BMI>30kg/m2) {HR 2.37 (1.51-3.71) (p<0.001)}, smoking {HR 2.05 (1.33-3.15) (p<0.001)} and being on antihypertensive treatment {HR 2.25 (1.46-3.46) (p<0.001)}. CONCLUSION: Apart from smoking, which increases the risk of CA in general, the midlife risk factor pattern differs between CA of cardiac and non-cardiac origin. Whereas CA of cardiac origin is predicted by history of cardiovascular disease, dyslipidemia and diabetes mellitus, the main risk factors for CA of non-cardiac origin are obesity and hypertension. In addition to control of classical cardiovascular risk factors for prevention of CA, our results suggest that prevention of midlife obesity may reduce the risk of CA of non-cardiac origin.

Ischemic stroke rates decline in patients with atrial fibrillation as anticoagulants uptake improves: A Swedish cohort study.

INTRODUCTION: The impact of the increased anticoagulants uptake on incidence rate of ischemic stroke is largely unknown. We assessed time trends in rates of ischemic stroke in patients with incident atrial fibrillation (AF) diagnosed between 2011 and 2013. MATERIALS AND METHODS: Population-based retrospective registry study of all 11,500 adults diagnosed with incident non-valvular atrial fibrillation in 2011-2013 in primary and secondary care and receiving oral anticoagulants (n=4847), aspirin (n=2850) or no treatment (n=3766) in Skåne County, Sweden. The primary outcome was the rate of ischemic stroke within 365days after AF diagnosis. RESULTS AND CONCLUSION: Cumulative incidence of ischemic stroke decreased from 2.87% (95% confidence interval (CI) 2.37-3.45%) to 1.93% (95% CI 1.54-2.41%) while the uptake of oral anticoagulants increased from 36.6% to 48.4% between 2011 and 2013 (regression coefficient -0.08; 95% CI, -0.09 to -0.07, p<0.001). The increased uptake of oral anticoagulants in the community is associated with decreased incidence of ischemic stroke in AF patients.

Risk factor changes and incident atrial fibrillation among middle-aged men in the Malmö Preventive Project cohort.

AIMS: To determine whether risk factor changes over 6 years were associated with the incidence of atrial fibrillation (AF) among middle-aged men in the Malmö Preventive Project (MPP) cohort. METHODS AND RESULTS: In total, 5633 men (mean age 47.0 years at baseline) underwent two screening examinations, separated by an average of 6 years. The annual rate at which systolic blood pressure (SBP), diastolic blood pressure (DBP), weight, fasting blood glucose (FBG), blood glucose at 2-h oral glucose tolerance test (OGTT), and screening spirometry values changed was calculated and analysed in relation to incident AF, using Cox and competing risks regression to determine hazard ratios (HRs) and 95% confidence intervals (CIs). Mean follow-up time ± SD from rescreening was 22.3 ± 7.4 years. Significant associations were found between the annual increase of SBP (HR: 1.04, 95% CI: 1.01-1.07, P = 0.003 per mmHg), DBP (HR: 1.06, 95% CI: 1.01-1.1, P = 0.024 per mmHg), FBG (HR: 2.11, 95% CI: 1.44-3.12, P < 0.0001 per mmol/L), and weight (HR: 1.14, 95% CI: 1.05-1.24, P = 0.003 per kg) on the one hand and incident AF on the other, after full adjustment for baseline age, height, weight, SBP, FBG, smoking status, sedentary lifestyle, anti-hypertensive treatment, screening year, and low socioeconomic status. CONCLUSION: The age-adjusted annual rates of increase in SBP, DBP, weight, and FBG in mid-life are associated with AF incidence in men. This raises the question of whether preventive measures directed at individuals with high annual increases, even within the normal range, would reduce AF incidence.

Validation of the good outcome following attempted resuscitation score on in-hospital cardiac arrest in southern Sweden.

BACKGROUND: There is a great need for a simple and clinically useful instrument to help physicians estimate the probability of survival to discharge with a good neurological outcome (cerebral performance category, CPC=1) in cases of in-hospital cardiac arrest (IHCA). Our aim was to validate the "Good Outcome Following Attempted Resuscitation" (GO-FAR) score in a different country with different demographics than previously investigated. METHODS: A retrospective observational study including all cases of IHCA who were part of a cardiac arrest registry at Skåne University Hospital in Sweden 2007-2010. RESULTS: Two-hundred-eighty-seven patients suffered IHCA during the period. A majority were male and mean age was 70years. Overall survival to discharge independent of neurological function was 20.2%; 78% of the survivors had CPC=1 and survival to discharge with CPC=1 was 15.7%. The area under the receiver operating characteristics curve for the GO-FAR score was 0.85 (CI=0.78-0.91, p<0.001), consistent with very good discrimination. Patients in the group with low or very low probability of survival had a likelihood of 2.8% (95% CI 0.0-6.7), whereas the groups with average and above average probabilities had likelihoods of 8.2% (3.7-13) and 46% (34-58), respectively, for good neurological outcome. This compares with likelihoods of 1.6%, 9.2% and 27.8% in the original study. CONCLUSION: The GO-FAR score accurately predicted the probability of survival to discharge with CPC=1, even when applied to a different population in another country.

Antithrombotic therapy in patients with non-valvular atrial fibrillation in Southern Sweden: A population-based cohort study.

INTRODUCTION: Oral anticoagulants in patients with atrial fibrillation (AF) with moderate-to-high stroke risk are strongly recommended by the current guidelines. MATERIALS AND METHODS: Population-based register study of all 13,837 patients with incident non-valvular AF diagnosed during 2011-2014 in primary and secondary care (including all in- and outpatient visits) in Skåne County, Sweden. The outcome was the prescription of direct-acting oral anticoagulants (DOAC), warfarin or acetylsalicylic acid (ASA). RESULTS AND CONCLUSION: Guideline adherence increased from 47.6% in 2011 to 66.1% in 2014, mostly due to decrease in undertreatment. In patients with CHA2DS2-VASc score ≥ 2, ASA uptake decreased from 29.9% to 14.7% and DOAC uptake increased from 2.1% to 25.1%. The use of ASA was more common among elderly and with increasing stroke- and bleeding risk. Overall, 47.4% of patients with CHA2DS2-VASc score ≥ 2 did not receive oral anticoagulants. Undertreatment was particularly common in women < 65 years (55.8%) and in patients > 84 years (65.3% in women and 62% in men). Overtreatment of patients at low stroke risk was 35.9% in men and 36.4% in women. Provider speciality affected the choice of treatment only to a minor degree. Despite increasing guideline adherence, there is a suboptimal use of antithrombotic therapy in a large proportion of AF patients diagnosed in different clinical settings. Efforts to further improve guideline adherence should particularly be targeted on women < 65 years, elderly > 84 years and patients at low stroke risk.

Cyclooxygenase inhibition causes marked impairment of renal function in elderly subjects treated with diuretics and ACE-inhibitors.

BACKGROUND: Treatment with angiotensin-converting enzyme (ACE)-inhibitors is known to cause an initial reduction in glomerular filtration rate (GFR) in patients with congestive heart failure. The long-term beneficial effects of ACE-inhibitors in these patients can be counteracted by cyclooxygenase-inhibitors. AIMS: To quantify the negative renal effects of the cyclooxygenase-inhibitor diclofenac in elderly healthy subjects and to assess how treatment with an ACE-inhibitor, after activation of the renin-angiotensin system, influences these renal effects. METHODS: Fourteen elderly, healthy subjects received oral diclofenac and placebo in a double-blind cross-over fashion. The study was divided in two parts; in part one, subjects received no pre-treatment and in part two, the subjects were given pre-treatment with bendroflumethiazide and enalapril in order to activate the renin-angiotensin system. RESULTS: Diclofenac induced significant (p<0.05) decreases in GFR, urine flow, excretion rates of sodium and potassium, electrolyte clearance, osmolality clearance and free water clearance both with and without renin-angiotensin system activation. Least square means (95% CI) of all observations during the first 6 h after dosing showed that diclofenac caused a reduction in GFR from 71 (64-78) to 59 (52-66) ml/min. After pre-treatment, diclofenac further reduced GFR from 60 (52-67) to 48 (40-55) ml/min. After diclofenac administration, urine flow fell from 7.4 (6.4-8.3) to 5.1 (4.2-6.1) ml/min, after pre-treatment, diclofenac gave a further reduction from 4.1 (3.1-5.1) to 2.2 (1.3-3.2) ml/min. More than half of the reductions were caused by the pre-treatment. CONCLUSION: Renal function in elderly, healthy subjects is impaired after acute intake of diclofenac. This impairment is observed both with and without activation of the renin-angiotensin system and ACE-inhibitor treatment but is more pronounced after pre-treatment.

Concomitant use of dronedarone with dabigatran in patients with atrial fibrillation in clinical practice.

INTRODUCTION: Dronedarone is a strong P-glycoprotein inhibitor with a potential to increase bioavailability of dabigatran. We sought to measure and report plasma concentrations of dabigatran in patients with atrial fibrillation (AF) on concomitant dronedarone treatment. MATERIALS AND METHODS: A cohort of 33 patients (mean age 64 years, 16 men) concomitantly treated with dabigatran at a dose of 110 mg twice a day (bid) and dronedarone at a dose of 400mg bid at the discretion of the patient's cardiologist were followed prospectively. RESULTS: Median trough plasma concentration of dabigatran at one week and one month after the concomitant treatment start was 102.0 (range 8-251) ng/ml and 84 (range 27-302) ng/ml respectively. Median treatment length was 13 (range 1-21) months. There was one major bleeding event (2,8% per patient-year) and no thrombotic events during a total of 35.5 patient-years. CONCLUSIONS: Median trough plasma concentration of dabigatran in our study was observed to be similar to median trough plasma concentration of dabigatran at a dose of 150 mg bid without concomitant dronedarone in earlier studies with low reported rate of bleeding and thrombosis. Since concomitant treatment offers potential benefits to patients with AF, larger future trials that might refute the current contraindication are warranted.