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Biomedical subjects

A K Pedersen

Publications and source records attributed to A K Pedersen.

At least 19 recordsLinked to original sources

Incidence of atrial fibrillation and thromboembolism in a randomised trial of atrial versus dual chamber pacing in 177 patients with sick sinus syndrome.

OBJECTIVE: To analyse the occurrence of atrial fibrillation (AF) and thromboembolism in a randomised comparison of rate adaptive single chamber atrial pacing (AAIR) and dual chamber pacing (DDDR) in patients with sick sinus syndrome and normal atrioventricular (AV) conduction, in which left atrial dilatation and decreased left ventricular fractional shortening had been observed in the DDDR group. METHODS: 177 consecutive patients with sick sinus syndrome (mean (SD) age 74 (9) years, 104 women) were randomly assigned to treatment with one of three pacemakers: AAIR (n = 54), DDDR with a short rate adaptive AV delay (n = 60) (DDDR-s); or DDDR with a fixed long AV delay (n = 63) (DDDR-l). Analysis was intention to treat. RESULTS: Mean follow up was 2.9 (1.1) years. AF at one or more ambulatory visits was significantly less common in the AAIR group (4 (7.4%) v 14 (23.3%) in the DDDR-s group v 11 (17.5%) in the DDDR-l group; p = 0.03, log rank test). The risk of developing AF in the AAIR group compared with the DDDR-s group was significantly decreased after adjustment for brady-tachy syndrome in a Cox regression analysis (relative risk 0.27, 95% confidence interval (CI) 0.09 to 0.83, p = 0.02). The benefit of AAIR was highest among patients with brady-tachy syndrome. Brady-tachy syndrome and a thromboembolic event before pacemaker implantation were independent predictors of thromboembolism during follow up (relative risk 7.5, 95% CI 1.6 to 36.2, p = 0.01, and relative risk 4.7, 95% CI 1.2 to 17.9, p = 0.02, respectively). CONCLUSIONS: During a mean follow up of 2.9 years AAIR was associated with significantly less AF. The beneficial effect of AAIR was still significant after adjustment for brady-tachy syndrome. Brady-tachy syndrome was associated with an increased risk of thromboembolism.

Adult↗

Task Force on Sudden Cardiac Death, European Society of Cardiology.

The European Society of Cardiology has convened a Task Force on Sudden Cardiac Death in order to provide a comprehensive, educational document on this important topic. The main document has been published in the European Heart Journal in August 2001. The Task Force has now summarized the most important clinical issues on sudden cardiac death and provided tables with recommendations for risk stratification and for prophylaxis of sudden cardiac death. The present recommendations are specifically intended to encourage the development and revision of national guidelines on prevention of sudden cardiac death. The common challenge for cardiologists, physicians of other medical specialties and health professionals throughout Europe is to realize the potential for sudden cardiac death prevention and to contribute to public health efforts to reduce its burden.

Advisory Committees↗

Electromechanical mapping for detection of myocardial viability in patients with ischemic cardiomyopathy.

BACKGROUND: We evaluated the ability of electromechanical mapping of the left ventricle to distinguish between nonviable and viable myocardium in patients with ischemic cardiomyopathy. METHODS AND RESULTS: Unipolar voltage amplitudes and local endocardial shortening were measured in 31 patients (mean+/-SD age, 62+/-8 years) with ischemic cardiomyopathy (ejection fraction, 30+/-9%). Dysfunctional regions, identified by 3D echocardiography, were characterized as nonviable when PET revealed matched reduction of perfusion and metabolism and as viable when perfusion was reduced or normal and metabolism was preserved. Mean unipolar voltage amplitudes and local shortening differed among normal, nonviable, and viable dysfunctional segments. Coefficient of variation for local shortening exceeded differences between groups and did not allow distinction between normal and dysfunctional myocardium. Optimum nominal discriminatory unipolar voltage amplitude between nonviable and viable dysfunctional myocardium was 6.5 mV, but we observed a great overlap between groups. Individual cutoff levels calculated as a percentage of electrical activity in normal segments were more accurate in the detection of viable dysfunctional myocardium than a general nominal cutoff level. The optimum normalized discriminatory value was 68%. Sensitivity and specificity were 78% for the normalized discriminatory value compared with 69% for the nominal value (P:<0.02). CONCLUSIONS: Endocardial ECG amplitudes in patients with ischemic cardiomyopathy display a wide scatter, complicating the establishment of exact nominal values that allow distinction between viable and nonviable areas. Individual normalization of unipolar voltage amplitudes improves diagnostic accuracy. Electroanatomic mapping may enable identification of myocardial viability.

Body Surface Potential Mapping↗

Two mutants of human heparin binding protein (CAP37): toward the understanding of the nature of lipid A/LPS and BPTI binding.

Heparin binding protein (HBP) is an inactive serine protease homologue with important implications in host defense during infections and inflammations. Two mutants of human HBP, [R23S,F25E]HBP and [G175Q]HBP, have been produced to investigate structure-function relationships of residues in the putative lipid A/lipopolysaccharide (LPS) binding site and BPTI (bovine pancreatic trypsin inhibitor) binding site. The X-ray structures have been determined at 1.9 A resolution for [G175Q]HBP and at 2.5 A resolution for the [R23S,F25E]HBP mutant, and the structures have been fully refined to R-factors of 18.2 % and 20.7 %, respectively. The G175Q mutation does not alter the overall structure of the protein, but the ability to bind BPTI has been eliminated, and the mutant mediates only a limited stimulation of the LPS-induced cytokine release from human monocytes. The lipid A/LPS binding property of [G175Q]HBP is comparable with that of native HBP. The R23S,F25E mutations do not affect the binding of lipid A/LPS and BPTI or the LPS-induced cytokine release from human monocytes. This shows that two diverse ligands, lipid A/LPS and BPTI, do not share binding sites. Previously, there was convincing evidence for the proposed lipid A/LPS binding site of HBP. Unexpectedly, the extensive structural changes introduced by mutation of Arg23 and Phe25 do not affect the binding of lipid A/LPS, indicating that another not yet identified site on HBP is involved in the binding of lipid A/LPS.

Animals↗

AV block and changes in pacing mode during long-term follow-up of 399 consecutive patients with sick sinus syndrome treated with an AAI/AAIR pacemaker.

This retrospective study included a large cohort of consecutive patients primarily implanted at Skejby University Hospital with an AAI/AAIR pacemaker because of sick sinus syndrome (SSS) from July 1981 to July 1999. The primary aim of the study was to analyze the risk of developing AV block during long-term follow-up. A secondary aim was to study the incidence and reasons for changes in pacing mode caused by other than AV block. A total of 399 patients (231 women, mean age 71 +/- 13.5 years) were identified. Mean follow-up was 4.6 +/- 3.4 years and occurred at death, reoperation with mode change, pacemaker explant, or end of study. During follow-up, 44 patients had a ventricular lead implanted with a mean delay of 2.8 +/- 3.1 years (range 1 day-10.4 years) after the primary implantation. A total of 30 patients received a ventricular lead because of AV block or AF with bradycardia (annual incidence 1.7%). Another 14 patients received a ventricular lead without having documented AV block or AF with pauses (annual incidence 0.8%). The present observational study documents that in patients with SSS treated with AAI/AAIR pacing, AV block requiring implantation of a ventricular lead occurs at a rate of 1.7% per year. It is considered that AAI/AAIR pacing is safe and reliable as treatment for patients with SSS and normal AV conduction.

Adolescent↗

Reproducibility of QT parameters derived from 24-hour ambulatory ECG recordings in healthy subjects.

AIM: To estimate the reproducibility of QT parameters derived from 24-hour ambulatory ECG recordings. METHOD: Ten healthy volunteers aged 25 to 41 years participated. In two 24-hour ambulatory ECG recordings obtained 1 day apart, the QT interval was measured manually at stable heart rates in approximately 16 periods during daytime and 6 periods during nighttime. The association between the QT and RR interval was described by linear regression for day and nighttime separately and the following QT parameters were calculated: the QT interval at heart rate 60 beats/min during daytime (QT(60)day), slope(day), slope(night), and the difference in QT(60) between day and nighttime (DeltaQT(60)). The QT parameters were assessed four times for each participant to discriminate method inaccuracy from day to day variation. The reproducibility was estimated as the coefficient of repeatability, the relative error, and the ratio between within-subject variability and between-subject variability. RESULTS: The coefficient of repeatability, the relative error and the ratio, respectively, were 19 ms, 1.8% and 0.5 for QT(60)day, 0.076, 21% and 0.68 for slope(day), 0.116, 43% and 1.37 for slope(night), and 37 ms, 325% and 1.19 for DeltaQT(60) when estimating the overall day to day reproducibility. Inaccuracy of QT measurement accounted for approximately 40% of this variation, whereas the error caused by selecting segments was small. CONCLUSION: QT(60)day has a high reproducibility and may with advantage replace the conventional QT interval measured on a resting ECG. To assess QT dynamics, the slope of the regression line during daytime is suitable and the short term reproducibility acceptable for clinical trials. Regarding slope(night) and DeltaQT(60), the variation is high and the parameters should be used with caution.

Adult↗

Bias of QT dispersion.

BACKGROUND: Prolonged QT dispersion (QTD) is associated with an increased risk of arrhythmic death but its accuracy varies substantially between otherwise similar studies. This study describes a new type of bias that can explain some of these differences. MATERIAL: One dataset (DiaSet) consisted of 356 subjects: 169 with diabetes, 187 nondiabetic control persons. Another dataset (ArrSet) consisted of 110 subjects with remote myocardial infarction: 55 with no history of arrhythmia and 55 with a recent history of ventricular tachycardia or fibrillation. METHODS: 12-lead surface ECGs were recorded with an amplification of 10 mm/mV at a paper speed of 50 mm/s. The QT interval was measured manually by the tangent-method. The bias depends on the magnitude of the measurement errors and the measurable part of the bias increases with the number of the repeated measurements of QT. RESULTS: The measurable bias was significant for both datasets and decreased for increasing QTD in the DiaSet (P < 0.001) and in the ArrSet (P = 0.11). The bias was 2.5 ms and 1.9 ms at QTD = 38 ms and 68 ms, respectively, in the ArrSet, and 7.5 ms and 2.8 ms at QTD = 19 ms and 55 ms, respectively, in the DiaSet. CONCLUSIONS: This study shows that random measurement errors of QT introduces a type of bias in QTD that decreases as the dispersion increases, thus reducing the separation between patients with low versus high dispersion. The bias can also explain some of the differences in the mean QTD between studies of healthy populations. Averaging QT over three successive beats reduces the bias efficiently.

Aged↗

Improving the reproducibility of QT dispersion measures.

BACKGROUND: The low reproducibility of the QT dispersion (QTD) method is a major reason why it is not used in clinics. The purpose of this study was to develop QT dispersion parameters with better reproducibility and identification of patients with a high risk of ventricular arrhythmia or death. METHODS AND RESULTS: Three institutions using different methods for measuring QT intervals provided QT databases, which included more than 3500 twelve-lead surface ECGs. The data represented low and high risk subjects from the following groups: the normal population EpiSet (survivors vs dead from cardiovascular causes), acute myocardial infarction patients AmiSet (survivors vs dead) and remote myocardial infarction patients ArrSet (with vs without a history of ventricular arrhythmia). The EpiSet, AmiSet, and the ArrSet contributed with N = 122, 0, and 110 ECGs for reproducibility analysis, and 3244, 446, and 100 ECGs for the analysis of prognostic accuracy. The prognostic accuracy was measured as the area under the Receiver Operator Curve. The QT intervals were divided into six QT pairs; the longest pair consisted of the longest and the shortest QT intervals etc. The QT dispersion trend (QTDT) was defined as the slope of the linear regression of the N longest QT pairs after estimation of missing QT intervals by interpolation of measured QT intervals. The QTMAD and the QTSTD methods were defined as twice the mean absolute deviation and the standard deviation of the N longest QT pairs. The reproducibility was improved by 27% and 19% in the EpiSet and the ArrSet relative to the reproducibility of QTD. The accuracy improved for the EpiSet and the ArrSet and was maintained for the AmiSet. CONCLUSIONS: By using the three longest and the three shortest QT intervals in QTDT, QTMAD, or QTSTD, the reproducibility improved significantly while maintaining or improving the prognostic accuracy compared to QTD.

Aged↗

Three dimensional echocardiography documents haemodynamic improvement by biventricular pacing in patients with severe heart failure.

OBJECTIVES: To quantify the short term haemodynamic effects of biventricular pacing in patients with heart failure and left bundle branch block by using three dimensional echocardiography. DESIGN: Three dimensional echocardiography was performed in 15 consecutive heart failure patients (New York Heart Association functional class III or IV) with an implanted biventricular pacing system. Six minute walk tests were performed to investigate the effect of biventricular pacing on exercise capacity. Data were acquired at sinus rhythm and after short term (2-7 days) biventricular pacing. RESULTS: Compared with baseline values, biventricular pacing significantly reduced left ventricular end diastolic volume (EDV) by mean (SD) 4.0 (5.1)% (p < 0.01) and end systolic volume (ESV) by 5.6 (6.4)% (p < 0.02). Mitral regurgitant fraction was significantly reduced by 11 (12.1)% (p < 0.003) and forward stroke volume (FSV) increased by 13.9 (18.6)% (p < 0.02). Exercise capacity was significantly improved with biventricular pacing by 48.4 (43.3)% (p < 0.00001). Regression analyses showed that the percentage increase in FSV independently predicted percentage improvement in walking distance (r(2) = 0.73, p < 0.0002). Both basal QRS duration and QRS narrowing predicted pacing efficacy, showing a significant correlation with %DeltaEDV, %DeltaESV, and %DeltaFSV. CONCLUSIONS: In five of 15 consecutive patients with heart failure and left bundle branch block, biventricular pacing induced a more than 15% increase in FSV, which predicted a more than 25% increase in walking distance and was accompanied by an immediate reduction in left ventricular chamber size and mitral regurgitation.

Adult↗

Impact of acute biventricular pacing on left ventricular performance and volumes in patients with severe heart failure. A tissue doppler and three-dimensional echocardiographic study.

OBJECTIVES: We used tissue velocity imaging (TVI) and three-dimensional echocardiography to evaluate the effect of acute biventricular pacing on left ventricular (LV) performance and volumes in patients with severe heart failure and bundle branch block. BACKGROUND: Biventricular pacing causes acute hemodynamic improvement in patients with severe heart failure, and QRS duration has been used as a predictor of improved resynchronization. Tissue velocity has the potential of demonstrating the degree of LV resynchronization and three-dimensional echocardiography enables accurate quantitation of LV volumes and function. METHODS: TVI and three-dimensional echocardiography were performed during sinus rhythm and biventricular pacing in 25 consecutive patients with severe heart failure. RESULTS: Biventricular pacing significantly improved the extent of contracting myocardium in synchrony by 15.4% and the duration of contraction synchrony by 17% (p < 0.05 for both). Furthermore, end-diastolic and end-systolic volumes decreased by 7 +/- 4.5% and 13 +/- 6% (p < 0.01) and ejection fraction increased by 22.8 +/- 9% (p < 0.01). Baseline duration of QRS and the preejection period as well as the extent of myocardium with asynchronous contraction measured by TVI predicted pacing efficacy. In multivariate analysis, only the extent of myocardium with asynchronous contraction at the LV base predicted biventricular pacing efficacy. CONCLUSION: Biventricular pacing improves LV systolic performance and reduces LV volumes during short-term treatment. TVI provides important pathophysiological information on the degree of LV resynchronization and may contribute to improved patient selection.

Bundle-Branch Block↗

Regional myocardial blood flow in patients with sick sinus syndrome randomized to long-term single chamber atrial or dual chamber pacing--effect of pacing mode and rate.

OBJECTIVES: This study aimed to evaluate regional myocardial blood flow (MBF) and global left ventricular ejection fraction (LVEF) during chronic pacing in patients with sick sinus syndrome (SSS) randomized to either single chamber atrial (AAI) or dual chamber (DDD) pacing. BACKGROUND: Experimental studies indicate that chronic pacing in the right ventricular apex changes regional MBF, thereby compromising left ventricular function. METHODS: Thirty patients (age 74 +/- 10 years) were randomized to AAI (n = 15) or DDD (n = 15) pacemakers. After 22 +/- 7 months of pacing, MBF was quantified with 13N-labeled ammonia positron emission tomography scanning at 60 beats per min and 90 beats per min. Patients in the DDD group furthermore underwent MBF measurement at temporary AAI pacing, 60 beats per min. Myocardial blood flow was assessed in the anterior, lateral, inferior and septal regions, and the global mean MBF was calculated. Left ventricular ejection fraction was determined by echocardiography at pacemaker implantation and at the time of MBF measurements. RESULTS: Myocardial blood flow at rates 60 and 90 beats per min did not differ between the AAI and DDD groups. During temporary AAI pacing in the DDD group, MBF was significantly higher than during DDD pacing in both the inferior (p = 0.001) and septal (p = 0.004) regions and also globally (0.61 +/- 0.15 vs. 0.53 +/- 0.13 mL x g(-1) x min(-1), p = 0.005). In the DDD group, LVEF decreased from pacemaker implantation to time of MBF measurements (0.61 +/- 0.09 vs. 0.56 +/- 0.07, p = 0.013). Left ventricular ejection fraction during temporary AAI pacing at time of MBF measurements was not different from LVEF at pacemaker implantation. CONCLUSIONS: In patients with SSS, chronic DDD pacing reduced inferior, septal and global mean MBF as well as LVEF, as compared with temporary AAI pacing. The LVEF reversed to baseline level during temporary AAI pacing despite 22 months of permanent ventricular pacing preceding it. Augmenting pace rate to 90 beats per min increased MBF equally in the two treatment groups.

Aged↗

Dose-related cardiac electrophysiological effects of intravenous magnesium. A double-blind placebo-controlled dose-response study in patients with paroxysmal supraventricular tachycardia.

AIMS: The role of magnesium as an antiarrhythmic drug is yet not conclusive. Therefore, we performed a double-blind, randomized, placebo-controlled dose-response study of cardiac electrophysiological effects of intravenous magnesium. METHODS AND RESULTS: Thirty-six patients undergoing an electrophysiological evaluation for paroxysmal supraventricular tachycardia were randomized to one of the following dosages of intravenous magnesium (0, 5, 10 or 20 mmol). Conventional electrophysiological variables for sinus node function, atrial, atrioventricular node and ventricular conduction and refractoriness were measured before and after magnesium administration. Prolongation of the atrial-His interval was found at 5 mmol of magnesium compared with placebo and no further prolongation was observed at higher doses (-3 +/- 8, 11 +/- 9, 7 +/- 15, 11 +/- 16, for the dosages of 0, 5, 10 and 20 mmol of magnesium, respectively, P < 0.05). Measures of sinus node function, intra-atrial conduction and conduction through the Purkinje system were unaffected by magnesium. Male gender was associated with prolongation in atrial effective refractory period, in contrast to shortening in females: 2 +/- 43, 35 +/- 44, 36 +/- 33, 13 +/- 12 ms for males and 3 +/- 6, -12 +/- 11, -13 +/- 12, 0 +/- 23 ms for females, respectively (P < 0.001). CONCLUSION: Atrioventricular node conduction was prolonged by 5 mmol intravenous magnesium and no further prolongation was observed at higher dosages. At dosages of 5 and 10 mmol magnesium the atrial effective refractoriness was prolonged in males and shortened in females.

Adolescent↗

Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy.

We identified the alpha-cardiac actin gene (ACTC) as a novel disease gene in a pedigree suffering from familial hypertrophic cardiomyopathy (FHC). Linkage analyses excluded all the previously reported FHC loci as possible disease loci in the family studied, with lod scores varying between -2.5 and -6.0. Further linkage analyses of plausible candidate genes highly expressed in the adult human heart identified ACTC as the most likely disease gene, showing a maximal lod score of 3.6. Mutation analysis of ACTC revealed an Ala295Ser mutation in exon 5 close to 2 missense mutations recently described to cause the inherited form of idiopathic dilated cardiomyopathy (IDC). ACTC is the first sarcomeric gene described in which mutations are responsible for 2 different cardiomyopathies. We hypothesize that ACTC mutations affecting sarcomere contraction lead to FHC and that mutations affecting force transmission from the sarcomere to the surrounding syncytium lead to IDC.

Actins↗

[Single-chamber atrial pacing is better than single chamber ventricular pacing in patients with sick sinus syndrome. Results of long-term follow up in a prospective randomized study].

In a study of 225 patients with sick sinus syndrome randomized to single chamber atrial pacing (n = 110) or ventricular pacing (n = 115), atrial pacing was associated with less atrial fibrillation and thromboembolism after 3.3 years follow-up. To determine whether this beneficial effect of atrial pacing is maintained at long-term, follow-up was extended. Follow-up visits were at 3 months, 12 months, and then once every year, and included physical examination, ECG, and pacemaker check-up. After 5.5 years follow-up, all-cause mortality, cardiovascular deaths, atrial fibrillation, thromboembolism, and heart failure were significantly less in the atrial group. AV block occurred in four patients in the atrial group. The beneficial effect of atrial pacing observed previously is enhanced substantially after extended follow-up. Patients with sick sinus syndrome should be treated with an atrial pacing system.

Aged↗

QT dispersion in patients with arrhythmogenic right ventricular dysplasia.

AIMS: Arrhythmogenic right ventricular dysplasia is a rarely diagnosed cardiomyopathy, but a frequent cause of ventricular arrhythmia and sudden cardiac death. QT interval dispersion, measured as an interlead variability of QT, is a marker of dispersion of ventricular repolarization and, hence, of electrical instability. The present study was conducted to assess the occurrence of QT dispersion and its modulation during treatment with sotalol. Methods Twenty-five patients with the diagnosis of arrhythmogenic right ventricular dysplasia were studied retrospectively. Fourteen patients were considered low risk for malignant ventricular arrhythmia and sudden cardiac death, and 11 high risk due to documented sustained ventricular arrhythmia, cardiac arrest, or sudden cardiac death. Twenty five healthy volunteers served as control subjects. RESULTS: Dispersion of repolarization was significantly higher in patients than in control subjects (QTd and JTd: P<0.05). Dispersion of repolarization was equal in patients both with and without malignant arrhythmias. There was no significant change in dispersion after treatment with sotalol. Adjacent QT dispersion between leads V3-V4, V4-V5 and V5-V6, respectively, was higher in patients than in control subjects (P<0. 05), while no differences were seen in leads V1-V2 and V2-V3. CONCLUSION: QT interval dispersion is increased in patients with arrhythmogenic right ventricular dysplasia. However, the degree of dispersion is not related to the severity of symptoms, nor is it influenced by treatment with sotalol.

Adolescent↗