Frequency and risk factors of atrial fibrillation after acute abdominal surgery: A prospective cohort study.

BACKGROUND AND AIM: Scarce data exist on the true incidence of postoperative atrial fibrillation (POAF) after acute abdominal surgery and associated outcomes. The current study aimed to identify the frequencies of clinically recognized POAF and associated complications, along with their risk factors. METHODS: This study was a prospective, single-center cohort study of unselected adult patients referred for acute abdominal surgery during a 3-month period. Through careful review, demographics, comorbidity, and surgical characteristics were prospectively drawn from medical charts. The primary outcome was clinically recognized POAF occurring in-hospital. Logistic regression was used to determine the risk factors of POAF and associated complications. A subgroup was enrolled in a feasibility study of peri- and postoperative continuous cardiac rhythm monitoring. RESULTS: In total, 450 patients were enrolled. Clinically recognized in-hospital POAF was observed in 22 patients (4.9%). All cases were observed in patients aged ≥60 years, corresponding to 22 of 164 patients (13.4%). Multiple risk factors were observed, such as age, prior atrial fibrillation, heart failure, hypertension, diabetes mellitus, chronic renal disease, and major (vs. minor) surgery. POAF was associated with severe in-hospital complications (POAF group 45.5% vs. non-POAF group 8.6%, p < .001) and in-hospital mortality (POAF group 13.6% vs. non-POAF group 3.0%, p = .043). In total, 295 patients were monitored by continuous cardiac rhythm monitoring for 12,148 h, yielding five patients with asymptomatic AF. CONCLUSIONS: In conclusion, this prospective study of POAF in patients undergoing acute abdominal surgery showed that one in 20 patients developed clinically recognized in-hospital POAF. Multiple risk factors of POAF were identified. POAF was associated with severe complications up to 30 days after surgery.

The left atrial appendage closure by surgery-2 (LAACS-2) trial protocol rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk.

BACKGROUND: Current recommendations regarding the use of surgical left atrial appendage (LAA) closure to prevent thromboembolisms lack high-level evidence. Patients undergoing open-heart surgery often have several cardiovascular risk factors and a high occurrence of postoperative atrial fibrillation (AF)-with a high recurrence rate-and are thus at a high risk of stroke. Therefore, we hypothesized that concomitant LAA closure during open-heart surgery will reduce mid-term risk of stroke independently of preoperative AF status and CHA2DS2-VASc score. METHODS: This protocol describes a randomized multicenter trial. Consecutive participants ≥18 years scheduled for first-time planned open-heart surgery from cardiac surgery centers in Denmark, Spain, and Sweden are included. Both patients with a previous diagnosis of paroxysmal or chronic AF, as well as those without AF, are eligible to participate, irrespective of their CHA2DS2-VASc score. Patients already planned for ablation or LAA closure during surgery, with current endocarditis, or where follow-up is not possible are considered noneligible. Patients are stratified by site, surgery type, and preoperative or planned oral anticoagulation treatment. Subsequently, patients are randomized 1:1 to either concomitant LAA closure or standard care (ie, open LAA). The primary outcome is stroke, including transient ischemic attack, as assigned by 2 independent neurologists blinded to the treatment allocation. To recognize a 60% relative risk reduction of the primary outcome with LAA closure, 1,500 patients are randomized and followed for 2 years (significance level of 0.05 and power of 90%). CONCLUSIONS: The LAACS-2 trial is likely to impact the LAA closure approach in most patients undergoing open-heart surgery. TRIAL REGISTRATION: NCT03724318.

Are Prolonged Ventricular Pauses in Atrial Fibrillation a Marker of Poor Prognosis?

BACKGROUND: In patients with atrial fibrillation (AF), the long-term prognosis of long electrocardiographic pauses in the ventricular action is not well studied. METHODS: Consecutive Holter recordings in patients with AF (n = 200) between 2009 and 2011 were evaluated, focusing on pauses of at least 2.5 s. Outcomes of interest were all-cause mortality and pacemaker implantation. RESULTS: Forty-three patients (21.5%) had pauses with a mean of 3.2 s and an SD of 0.9 s. After a median follow-up of 99 months (ranging 89-111), 47% (20/43) of the patients with and 45% (70/157) without pauses were deceased. Pauses of ≥2.5 s did not constitute a risk of increased mortality: HR = 0.75 (95% CI: 0.34-1.66); p = 0.48, neither did pauses of ≥3.0 s: HR = 0.43 (95% CI: 0.06-3.20); p = 0.41. Sixteen percent of patients with pauses underwent pacemaker implantation during follow-up. Only pauses in patients referred to Holter due to syncope and/or dizzy spells were associated with an increased risk of pacemaker treatment: HR = 4.7 (95% CI: 1.4-15.9), p = 0.014, adjusted for age, sex, and rate-limiting medication. CONCLUSION: In patients with AF, prolonged electrocardiographic pauses of ≥2.5 s or ≥3.0 s are not a marker for increased mortality in this real-life clinical study.

Effects of liraglutide on diastolic function parameters in patients with type 2 diabetes and coronary artery disease: a randomized crossover study.

BACKGROUND: Diastolic dysfunction is highly prevalent in patients with type 2 diabetes mellitus (T2DM) and is associated with overweight, glucose dysregulation and coronary artery disease (CAD). The GLP-1 receptor agonist, liraglutide, has shown to induce weight loss and improve metabolic factors, thus modulating factors associated with diastolic dysfunction. We have previously reported the effects of liraglutide on systolic function, and in this current study we explore the effects of liraglutide on diastolic function parameters in patients with stable CAD, preserved left ventricular ejection fraction (LVEF), and newly diagnosed T2DM. METHODS: Thirty subjects were randomized to liraglutide or placebo intervention for 12 + 12-weeks in this double-blind cross-over study. 2D-echocardiography using tissue velocity imaging was used for assessment of diastolic function parameters. Early diastolic filling velocity (E), late atrial filling velocity (A), E-wave deceleration time (EDT) and E/A ratio was assessed from the pulse wave (PW)-Doppler velocity recording of the mitral inflow. Peak early diastolic annular velocities (e') was measured from color tissue doppler images. RESULTS: Liraglutide, when compared to placebo, induced a significant reduction in average e' and lateral e' velocities (- 0.57 cm/s [- 1.05 to - 0.08] and -0.74 cm/s [-1.32 to -0.15], respectively). Adjusted for the concomitant increase in HR (+ 6.16 bpm [0.79 to 11.54], the changes were not significant. No significant changes in other diastolic function parameters were observed. CONCLUSIONS: Liraglutide therapy did not improve any diastolic function parameters in subjects with T2DM, CAD, and preserved LVEF. Instead, a deterioration in e' was observed, which was associated to an increase in heart rate induced by liraglutide therapy. Trial registration Clinical Trial Registration: http://www.clinicaltrials.gov (unique identifier: NCT01595789) (first submitted May 8, 2012).

Night-time heart rate variability identifies high-risk people among people with uncomplicated type 2 diabetes mellitus.

BACKGROUND: Low heart rate variability (HRV) reflects cardiac autonomic neuropathy, which is associated with increased cardiovascular mortality in people with type 2 diabetes mellitus (T2DM). Measuring HRV is challenged by environmental noise, mental stress and physical activity during daytime. Night-time HRV during sleep may be a more valid tool to measure cardiac autonomic neuropathy and therefore may improve prediction of cardiovascular (CV) events in low-risk people with T2DM. METHODS: Copenhagen Holter Study included 678 community-dwelling participants aged 55-75 years who were free of previous CV disease. Day and night-time HRV were available for 653 participants. The population included 133 people with well-controlled T2DM and newly recognized T2DM (mean HbA1c 55 mmol/mol [7.2%]). HRV is defined as standard deviation for the mean value of normal-to-normal complexes (SDNN). Night-time HRV measurements were pre-defined from 2:00 to 2:15 AM. Cardiovascular events were defined as CV death, myocardial infarction, stroke or coronary revascularization. RESULTS: Median follow-up time was 14.4 years. During this period, 245 death and 149 CV events (CV death 36, myocardial infarction 42, revascularisation procedures 46, stroke 70) occurred in total. Among people with T2DM, 41 CV events were observed (CV death 13, myocardial infarction 13, revascularisation procedures 17, stroke 18). Night-time SDNN was inversely associated with CV events in people with T2DM, (hazard ratio [HR]: 0.74 95% confidence interval [CI]:0.61-0.89) for each 10-millisecond increment in SDNN after adjustment for the conventional risk factors sex, age, LDL cholesterol, smoking, systolic blood pressure and by also including glucose CRP and NT-proBNP in adjustment. Twenty-four-hour HRV was not associated with CV events, but associated with all-cause mortality in people with T2DM. Conventional risk factors had a receiver operating characteristic (ROC) value of 0.704 (95% CI 0.602-0.806) to predict CV events in people with T2DM. The prediction of CV events by conventional risk factors was improved in people with T2DM by the addition of night-time SDNN; ROC 0.765 (95% CI 0.669-0.862), p = 0.037, but ROC was not improved by addition of CRP and NT-proBNP in the model. In people with T2DM and night-time SDNN ≤30 ms, the 10-year risk of CV death and CV event rate was 12% and 45%, respectively, which re-allocated them to a 'very high-risk' group according to current guidelines. CONCLUSION: Reduced night-time HRV predicts increased risk of CV events in people with well-controlled T2DM, thus night-time HRV may add to traditional risk factors in predicting CV events in people with T2DM.

A screening method to spot biomarkers that may warn of serious events in a chronic disease - illustrated by cardiological CLARICOR trial data.

OBJECTIVES: To develop a crude screening method for detecting biomarkers which frequently exhibit a rise (or fall) in level prior to a serious event (e.g. a stroke) in patients with a chronic disease, signalling that the biomarker may have an alarm-raising or prognostic potential. The subsequent assessment of the marker's clinical utility requires costly, difficult longitudinal studies. Therefore, initial screening of candidate-biomarkers is desirable. METHODS: The method exploits a cohort of patients with biomarkers measured at entry and with recording of first serious event during follow-up. Copying those individual records onto a common timeline where a specific event occurs on the same day (Day 0) for all patients, the baseline biomarker level, when plotted against the patient's entry time on the revised timeline, will have a positive (negative) regression slope if biomarker levels generally rise (decline) the closer one gets to the event. As an example, we study 1,958 placebo-treated patients with stable coronary artery disease followed for nine years in the CLARICOR trial (NCT00121550), examining 11 newer biomarkers. RESULTS: Rising average serum levels of cardiac troponin T and of N-terminal pro-B-type natriuretic peptide were seen prior to a fatal cardiovascular outcome. C-reactive protein rose prior to non-cardiovascular death. Glomerular filtration rate, seven lipoproteins, and nine newer cardiological biomarkers did not show convincing changes. CONCLUSIONS: For early detection of biomarkers with an alarm-raising potential in chronic diseases, we proposed the described easy procedure. Using only baseline biomarker values and clinical course of participants with coronary heart disease, we identified the same cardiovascular biomarkers as those previously found containing prognostic information using longitudinal or survival analysis.

P-wave indices as predictors of atrial fibrillation.

BACKGROUND: P-wave duration (PDURATION ) and P-wave area (PAREA ) have been linked to risk of atrial fibrillation (AF), but they do not improve the efficacy of Framingham AF risk score. We suggest the incorporation of both variables in one index, the P-wave area/P-wave duration (PAREA/DURATION ) index, which may be considered an expression of the average amplitude of the P wave that reflects aspects of P-wave morphology. OBJECTIVE: To assess the prognostic value of P-wave area/P-wave duration index (PAREA/DURATION index) in lead II together with other P-wave indices (PWIs) in incidence of AF in the Copenhagen Holter Study. METHODS: The study included 632 men and women, between 55 and 75 years with no apparent heart disease or AF. Baseline standard 12-lead Electrocardiography (ECGs) were analyzed manually. RESULTS: The median follow-up time was 14.7 (14.5;14.9) years. A total of 68 cases of AF and 233 cases of death were recorded. The restricted cubic spline method showed a U-shaped association between PAREA/DURATION and rate of AF. The lowest quintile of PAREA/DURATION index in lead II was associated with increased rate of AF, HR 2.80 (1.64-4.79). The addition of the new index to the Framingham model for AF improved the model in this population. The PAREA in lead II in its lowest quintile was also associated with increased rate of AF, HR 2.16 (1.25-3.75), but did not improve the Framingham model. PDURATION and P-wave terminal force (PTF) were not significantly associated with AF. CONCLUSION: A flat P wave as expressed by a small PAREA/DURATION index in lead II is associated with increased rate of incident AF beyond known AF risk factors.

Effect of liraglutide on estimates of lipolysis and lipid oxidation in obese patients with stable coronary artery disease and newly diagnosed type 2 diabetes: A randomized trial.

Elevated levels of non-esterified fatty acids (NEFA) play a role in insulin resistance, impaired beta-cell function and they are a denominator of the abnormal atherogenic lipid profile that characterizes obese patients with type 2 diabetes (T2DM). We hypothesized that the GLP-1 receptor agonist liraglutide, in combination with metformin, would reduce lipolysis. In a randomized, double-blind, placebo-controlled, cross-over trial, 41 T2DM patients with coronary artery disease were randomized and treated with liraglutide-metformin vs placebo-metformin during 12- + 12-week periods with a wash-out period of at least 2 weeks before and between the intervention periods. NEFA kinetics were estimated using the Boston Minimal Model of NEFA metabolism, with plasma NEFA and glucose levels measured during a standard 180-minute frequently sampled intravenous glucose tolerance test. Liraglutide-metformin reduced estimates of lipolysis. Furthermore, placebo-metformin increased estimates of lipid oxidation, while treatment with liraglutide eliminated this effect. We conclude that liraglutide exerts a clinically relevant reduction in estimates of lipolysis and lipid oxidation which is explained, in part, by improved insulin secretion, as revealed by an intravenous glucose tolerance test.

Common source of miscalculation and misclassification of P-wave negativity and P-wave terminal force in lead V1.

BACKGROUND: P-wave terminal force (PTF) > 4000 ms·µV and deep terminal negativity (DTN) are ECG markers of left atrial abnormality associated with both atrial fibrillation and stroke. When the precordial lead V1 is placed higher than the correct position in the fourth intercostal space, it may cause increased PTF and DTN. Several studies have documented that electrode misplacement, especially high placement, is common. The influence of electrode misplacement on these novel ECG markers has not previously been quantified. OBJECTIVE: The objective was to assess the influence of electrode misplacement on PTF and DTN. METHOD: 12-Lead ECGs were recorded in 29 healthy volunteers from the Department of Cardiology at the Copenhagen University Hospital of Bispebjerg. The precordial electrode V1 was placed in the fourth, third and second intercostal space, giving a total of 3 ECGs per subject. Continuous variables were compared using Dunnett's post-hoc test and categorical variables were compared using Fischer's exact test. RESULTS: High placement of V1 electrodes resulted in a more than three-fold increase of PTF (IC4 = 2267 ms·µV, IC2 = 7996 ms·µV, p-value < 0.001). There was a similar increase of DTN (IC4 = 0%, IC2 = 28%, p-value < 0.001). P-wave area and amplitude of the negative deflection increased, and P-wave area and amplitude of the positive deflection decreased. The P-wave shape changed from being predominantly positive or biphasic in IC4 to 90% negative in IC2. The PR-duration and P-wave duration were not altered by electrode placement. CONCLUSION: High electrode placement results in significant alteration of PTF and DTN in lead V1.

Assessing Optimal Blood Pressure in Patients With Asymptomatic Aortic Valve Stenosis: The Simvastatin Ezetimibe in Aortic Stenosis Study (SEAS).

BACKGROUND: Evidence for treating hypertension in patients with asymptomatic aortic valve stenosis is scarce. We used data from the SEAS trial (Simvastatin Ezetimibe in Aortic Stenosis) to assess what blood pressure (BP) would be optimal. METHODS: A total of 1767 patients with asymptomatic aortic stenosis and no manifest atherosclerotic disease were analyzed. Outcomes were all-cause mortality, cardiovascular death, heart failure, stroke, myocardial infarction, and aortic valve replacement. BP was analyzed in Cox models as the cumulative average of serially measured BP and a time-varying covariate. RESULTS: The incidence of all-cause mortality was highest for average follow-up systolic BP ≥160 mm Hg (4.3 per 100 person-years; 95% confidence interval [CI], 3.1-6.0) and lowest for average systolic BP of 120 to 139 mm Hg (2.0 per 100 person-years; 95% CI, 1.6-2.6). In multivariable analysis, all-cause mortality was associated with average systolic BP <120 mm Hg (hazard ratio [HR], 3.4; 95% CI, 1.9-6.1), diastolic BP ≥90 mm Hg (HR, 1.8; 95% CI, 1.1-2.9), and pulse pressure <50 mm Hg (HR, 1.8; 95% CI, 1.1-2.9), with systolic BP of 120 to 139 mm Hg, diastolic BP of 70 to 79 mm Hg, and pulse pressure of 60 to 69 mm Hg taken as reference. Low systolic and diastolic BPs increased risk in patients with moderate aortic stenosis. With a time-varying systolic BP from 130 to 139 mm Hg used as reference, mortality was increased for systolic BP ≥160 mm Hg (HR, 1.7; P=0.033) and BP of 120 to 129 mm Hg (HR, 1.6; P=0.039). CONCLUSIONS: Optimal BP seems to be systolic BP of 130 to 139 mm Hg and diastolic BP of 70 to 90 mm Hg in these patients with asymptomatic aortic stenosis and no manifest atherosclerotic disease or diabetes mellitus. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00092677.

Serum Potassium Is Positively Associated With Stroke and Mortality in the Large, Population-Based Malmö Preventive Project Cohort.

BACKGROUND AND PURPOSE: Low serum potassium is associated with stroke in populations with cardiovascular disease, hypertension, and diabetes mellitus but has not been studied in a mainly healthy population. We aimed to study the relation between serum potassium and incident stroke and mortality in the Malmö Preventive Project, a large cohort with screening in early mid-life and follow-up >25 years. METHODS: Serum potassium measurements and covariates were available in 21 353 individuals (79% men, mean age 44 years). Mean follow-up time was 26.9 years for stroke analyses and 29.3 years for mortality analyses. There were 2061 incident stroke events and 8709 deaths. Cox regression analyses adjusted for multiple stroke risk factors (age, sex, height, weight, systolic blood pressure, fasting blood glucose, serum sodium, current smoking, prevalent diabetes mellitus, prevalent coronary artery disease, and treatment for hypertension) were fitted. RESULTS: There was an independent, linear association between serum potassium, per mmol/L increase, and both stroke (hazard ratio, 1.33; 95% confidence interval, 1.17-1.52; P<0.0001) and mortality (hazard ratio, 1.20; 95% confidence interval, 1.13-1.28; P<0.0001). This was significant in subjects both older and younger than the median age (46.5 years), and there was evidence of an interaction with serum sodium. The association was positive and significant for both ischemic stroke and intracerebral hemorrhage and in both hypertensive and normotensive subjects. CONCLUSIONS: Serum potassium, measured in early mid-life, was linearly associated with both incidence of ischemic stroke and intracerebral hemorrhage and all-cause mortality. An interaction with serum sodium implies that factors related to electrolyte balance and incident hypertension may be mediating factors.

Mild Hypokalemia and Supraventricular Ectopy Increases the Risk of Stroke in Community-Dwelling Subjects.

BACKGROUND AND PURPOSE: Stroke is independently associated with the common conditions of hypokalemia and supraventricular ectopy, and we hypothesize that the combination of excessive supraventricular ectopic activity and hypokalemia has a synergistic impact on the prognosis in terms of stroke in the general population. METHODS: Subjects (55-75 years old) from the Copenhagen Holter Study cohort (N=671) with no history of atrial fibrillation or stroke were studied-including baseline values of potassium and ambulatory 48-hour Holter monitoring. Excessive supraventricular ectopic activity is defined as ≥30 premature atrial complexes per hour or any episodes of runs of ≥20. Hypokalemia was defined as plasma-potassium ≤3.6 mmol/L. The primary end point was ischemic stroke. Cox models were used. RESULTS: Hypokalemia was mild (mean, 3.4 mmol/L; range, 2.7-3.6). Hypokalemic subjects were older (67.0±6.94 versus 64.0±6.66 years; P<0.0001) and more hypertensive (165.1±26.1 versus 154.6±23.5 mm Hg; P<0.0001). Median follow-up time was 14.4 years (Q1-Q3, 9.4-14.7 years). The incidence of stroke was significantly higher in the hypokalemic group (hazard ratio, 1.84; 95% confidence interval, 1.04-3.28) after covariate adjustments, as well as in a competing risk analysis with death (hazard ratio, 1.51; 95% confidence interval, 1.12-2.04). Excessive supraventricular ectopic activity was also associated with stroke (hazard ratio, 2.23; 95% confidence interval, 1.33-3.76). The combination of hypokalemia and excessive supraventricular ectopic activity increased the risk of events synergistically. Stroke rate was 93 per 1000 patient-year (P<0.0001) in this group (n=17) compared with 6.9 (n=480); 11 (n=81), and 13 (n=93) per 1000 patient-year in the groups without the combination. CONCLUSIONS: The combination of hypokalemia and excessive supraventricular ectopy carries a poor prognosis in terms of stroke.

Liraglutide effects on beta-cell, insulin sensitivity and glucose effectiveness in patients with stable coronary artery disease and newly diagnosed type 2 diabetes.

AIMS: The aims of the study were to investigate the effects of the GLP-1 receptor agonist liraglutide as add-on to metformin on insulin sensitivity (Si) and glucose effectiveness (Sg) in addition to its positive effects on beta-cell function in overweight/obese patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). METHODS: The design of the study was a randomized, double-blind, placebo-controlled, cross-over trial in patients with stable CAD and newly diagnosed well-controlled T2DM. Patients were treated with liraglutide/metformin vs placebo/metformin for a 12 + 12-week period with ≥2-week wash-out. First phase insulin secretion (AIRg), Si and Sg were estimated by the Bergman Minimal Model, enabling calculation of beta-cell function; Disposition Index (DI) = AIRg × Si. A total of 30 patients from among 41 randomized were available for paired analysis. RESULTS: Baseline characteristics were: HbA1c 47 mmol/mol (SD 6), BMI 31.6 kg/m2 (SD 4.8), fasting plasma-glucose 6.9 mmol/L (IQR 6.1; 7.4) and HOMA-IR 4.9 (IQR 3.0; 7.5). Liraglutide treatment improved AIRg by 3-fold, 497 mU × L-1 × min (IQR 342; 626, P < .0001) and DI by 1-fold, 766 (SD 824, P < .0001). Despite a significant weight loss of -2.7 kg (-6.7; -0.6) during liraglutide treatment, we found no improvement in HOMA-IR, Si or Sg. Weight loss during liraglutide therapy did not result in a carry-over effect. CONCLUSION: Liraglutide as add-on to metformin induces a clinically significant improvement in beta-cell function in overweight/obese, high cardiovascular risk patients with newly diagnosed well-controlled T2DM and CAD. The effect of liraglutide on DI is mediated entirely by improved AIRg whereas the effects on Si and Sg are neutral.

Atrial ectopy and N-terminal pro-B-type natriuretic peptide as predictors of atrial fibrillation: a population-based cohort study.

AIMS: The risk of incident atrial fibrillation (AF) can be estimated by clinical parameters in the Framingham AF risk model. Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) and increased rate of premature atrial contractions (PACs) have been shown to be associated with AF, but the additive value of both of these biomarkers in the Framingham AF risk model has not been fully examined. METHODS AND RESULTS: A total of 646 subjects from the Copenhagen Holter Study (mean age 64.4 ± 6.8 years, 41.6% women) with no history of prior AF, stroke or cardiovascular disease were followed for the diagnosis of incident AF or death (median follow-up time 14.4 years). Median NT-proBNP was 6.7 pmol/L (IQR: 3.6-13.5), median PAC count was 1.4 beats/h (IQR: 0.6-4.5), 71 (11.0%) subjects developed AF, and 244 (37.8%) died. Multiple Cox regression including Framingham AF risk score, log-transformed NT-proBNP, and log-transformed PAC showed a significant increase in AF hazard risk [hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.14-1.85, P = 0.002; HR 1.23, 95% CI 1.09-1.39, P = 0.001]. The addition of PAC to the Framingham AF risk model significantly improved the time-dependent area under the receiver operating characteristic curve (AUC 65.6 vs. 72.6; P = 0.008), while the addition of NT-proBNP did not. CONCLUSION: Atrial fibrillation risk discrimination was significantly improved by the addition of PAC to the Framingham AF risk model, but not by the addition of NT-proBNP.

Effects of the glucagon-like peptide-1 receptor agonist liraglutide on systolic function in patients with coronary artery disease and type 2 diabetes: a randomized double-blind placebo-controlled crossover study.

BACKGROUND: Patients with type 2 diabetes (T2D) and coronary artery disease (CAD) have increased risk of cardiac dysfunction. The diabetic heart is characterized by increased fatty acid oxidation and reduced glucose uptake resulting in reduced cardiac efficiency. Glucagon-like peptide-1 (GLP-1) has shown to increase myocardial glucose uptake and to improve myocardial function. We examined the effect of the GLP-1 receptor agonist, liraglutide, on the systolic function of the left ventricle (LV) in patients with T2D and stable CAD. METHODS: In this placebo-controlled crossover study, 41 subjects with T2D and stable CAD were randomized to liraglutide or placebo and underwent dobutamine stress echocardiography (DSE) and exercise tolerance test at beginning and end of each intervention. The primary endpoint was changes in LV ejection fraction. Secondary endpoints were exercise capacity and other measures of systolic function: wall motion score index (WMSI), global longitudinal strain (GLS) and strain rate (GLSR). RESULTS: Liraglutide, when compared to placebo, did not improve LV ejection fraction at rest (+0.54 %; 95 % CI 2.38-3.45), at low stress (+0.03 %; 95 % CI 3.25-3.32), at peak stress (+1.12 %; 95 % CI 3.45-5.69), or at recovery (+4.06 %; 95 % CI 0.81-8.93). No significant changes in WMSI were observed at any stress levels. GLS and GLSR at rest did not improve. The maximal exercise capacity estimated by metabolic equivalents was not affected by liraglutide. CONCLUSION: In conclusion, liraglutide did not improve the systolic function of the left ventricle during DSE or the exercise capacity in patients with T2D and stable CAD. Clinical Trial Registration http://www.clinicaltrials.gov (unique identifier: NCT01595789).

Long-term prognostic significance of homocysteine in middle-aged and elderly.

OBJECTIVE: We investigated the association among increased levels of plasma homocysteine (Hcy), all-cause mortality, and cardiovascular events. METHODS: Hcy was measured in 670 middle-aged and elderly subjects with no previous manifest cardiovascular disease. The follow-up period was 15 years. RESULTS: Subjects with Hcy ≥ 10.8 µmol/l (n = 231) had a significant higher incidence of all-cause mortality (p < 0.001) and CV events (p < 0.001) compared with subjects with Hcy < 10.8 µmol/l (n = 439). However, there was no association on high levels of Hcy and VTE events or stroke. CONCLUSION: Increased levels of Hcy are associated with all-cause mortality and CV events.

The circadian variation of premature atrial contractions.

AIMS: The aim of the study was to assess a possible circadian variation of premature atrial contractions (PACs) in a community-based population and to determine if the daily variation could be used to assess a more vulnerable period of PACs in predicting later incidence of atrial fibrillation (AF). METHODS AND RESULTS: We studied 638 subjects between the ages of 55 and 75 years from the Copenhagen Holter Study who underwent up to 48 h electrocardiogram recording. Follow-up on cardiovascular endpoints was performed in 2013 with a median follow-up time of 14.4 years. According to previous studies, two subgroups were studied based on a cut-off point of ≥720 PACs/day termed frequent PACs (n = 66) and not frequent PACs with <720 PACs/day (n = 572). Based on median values, a circadian rhythm could not be demonstrated in the population as a whole and the group without frequent PACs. However, a circadian variation was observed in the group with frequent PACs, who had the fewest PACs/h during the night with a nadir at 6 am and then reaching a peak value in the afternoon at 3 pm. Runs of PACs in all subjects showed a similar circadian variation. Both PACs/h and runs of PACs seemed to follow the daily variation in heart rate. After adjusting for relevant risk factors, the risk of AF was equal in all time intervals throughout the day. CONCLUSION: Premature atrial contractions showed a circadian variation in subjects with frequent PACs. No specific time interval of the day was more predictive of AF than others.

Ambulatory cardiac arrhythmias in relation to mild hypokalaemia and prognosis in community dwelling middle-aged and elderly subjects.

AIMS: Severe hypokalaemia can aggravate arrhythmia tendency and prognosis, but less is known about risk of mild hypokalaemia, which is a frequent finding. We examined the associations between mild hypokalaemia and ambulatory cardiac arrhythmias and their prognosis. METHODS AND RESULTS: Subjects from the cohort of the 'Copenhagen Holter Study' (n = 671), with no history of manifest cardiovascular (CV) disease or stroke, were studied. All had laboratory tests and 48-h ambulatory electrocardiogram (ECG) recording. The median follow-up was 6.3 years. p-Potassium was inversely associated with frequency of premature ventricular complexes (PVCs) especially in combination with diuretic treatment (r = -0.22, P = 0.015). Hypokalaemia was not associated with supraventricular arrhythmias. Subjects at lowest quintile of p-potassium (mean 3.42, range 2.7-3.6 mmol/L) were defined as hypokalaemic. Cardiovascular mortality was higher in the hypokalaemic group (hazard ratio and 95% confidence intervals: 2.62 (1.11-6.18) after relevant adjustments). Hypokalaemia in combination with excessive PVC worsened the prognosis synergistically; event rates: 83 per 1000 patient-year in subjects with both abnormalities, 10 and 15 per 1000 patient-year in those with one abnormality, and 3 per 1000 patient-year in subjects with no abnormality. One variable combining hypokalaemia with excessive supraventricular arrhythmias gave similar results in univariate analysis, but not after multivariate adjustments. CONCLUSION: In middle-aged and elderly subjects with no manifest heart disease, mild hypokalaemia is associated with increased rate of ventricular but not supraventricular arrhythmias. Hypokalaemia interacts synergistically with increased ventricular ectopy to increase the risk of adverse events.

Troponin T and N-terminal pro B-Type natriuretic peptide and presence of coronary artery disease.

BACKGROUND: We tested the effects of exercise intensity, sampling intervals, degree of coronary artery stenosis, and demographic factors on circulating N-terminal pro B-Type natriuretic peptide (NT-pro-BNP) and cardiac Troponin T (cTnT) in subjects suspected of coronary artery disease (CAD). MATERIALS AND METHODS: A total of 242 subjects referred for diagnostic evaluation of possible CAD had blood samples obtained before, 5 min after, and again 20 h after a symptom-limited exercise test. RESULTS: Totally 40 subjects had CAD with ≥ 50% stenosis, 115 subjects had no stenosis and 87 subjects served as controls. In univariate analysis CAD-subjects had higher median baseline NT-pro-BNP-levels (85.3 ng/L) compared with non-CAD-subjects (41.3 ng/L) and controls (40.1 ng/L), both p < 0.001, but the association disappeared in multivariate analysis adjusted for age and gender. NT-pro-BNP increased similarly after exercise in CAD-subjects, non-CAD-subjects, and controls (median increase 8.14 ng/L) and the increase was positively associated with baseline NT-pro-BNP but not presence of CAD. Median baseline cTnT was 6.25 ng/L in CAD-subjects and 3.00 ng/L in non-CAD-subjects as well as controls, both p < 0.0001. Median ΔcTnT (baseline to 20 h after exercise) was higher in CAD-subjects than non-CAD-subjects and controls (0.62 ng/L vs. 0.0 ng/L, p < 0.001). A linear relationship between ΔcTnT and 'percent of predicted maximal heart rate achieved' was found in subjects with ≥ 70% stenosis (n = 24, r = 0.4067 p = 0.046). CONCLUSIONS: Baseline cTnT and ΔcTnT were found to be independently associated with CAD and also with exercise intensity in stable chest pain subjects. These properties were not identified for NT-pro-BNP.