Erik Agner

Effect of dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction : a randomised trial

BACKGROUND Arrhythmias cause much morbidity and mortality after myocardial infarction, but in previous trials, antiarrhythmic drug therapy has not been convincingly effective. Dofetilide, a new class III agent, was investigated for effects on all-cause mortality and morbidity in patients with left-ventricular dysfunction after myocardial infarction. METHODS In 37 Danish coronary-care units, 1510 patients with severe left-ventricular dysfunction (wall motion index < or = 1.2, corresponding to ejection fraction < or = 0.35) were enrolled in a randomised, double-blind study comparing dofetilide (n=749) with placebo (n=761). The primary endpoint was all-cause mortality. Secondary endpoints included cardiac and arrhythmic mortality and total arrhythmic deaths. Analyses were by intention to treat. FINDINGS No significant differences were found between the dofetilide and placebo groups in all-cause mortality (230 [31%] vs 243 [32%]), cardiac mortality (191 [26%] vs 212 [28%]), or total arrhythmic deaths (129 [17%] vs 140 [18%]). Atrial fibrillation or flutter was present in 8% of the patients at study entry. In these patients, dofetilide was significantly better than placebo at restoring sinus rhythm (25 of 59 vs seven of 56; p=0.002). There were seven cases of torsade de pointes ventricular tachycardia, all in the dofetilide group. INTERPRETATION In patients with severe left-ventricular dysfunction and recent myocardial infarction, treatment with dofetilide did not affect all-cause mortality, cardiac mortality, or total arrhythmic deaths. Dofetilide was effective in treating atrial fibrillation or flutter in this population.

Lack of evidence for low-dimensional chaos in heart rate variability.

Nonlinear Dynamics in Heart Rate. Introduction: The term chaos is used to describe erratic or apparently random time‐dependent behavior in deterministic systems. It has been suggested that the variability observed in the normal heart rate may be due to chaos, hut this question has not been settled.

Heart rate versus heart rate variability in risk prediction after myocardial infarction.

Heart Rate versus Heart Rate Variability. Introduction: The aim of this study was to evaluate and compare heart rate and heart rate variability (HRV) in risk prediction after acute myocardial infarction (MI) and to evaluate the effect of beta‐blocker treatment on the prognostic performance of heart rate and HRV.

Dynamics of spectral components of heart rate variability during changes in autonomic balance.

Frequency domain analysis of heart rate variability (HRV) has been proposed as a semiquantitative method for assessing activities in the autonomic nervous system. We examined whether absolute powers, normalized powers, and the low frequency-to-high frequency ratio (LF/HF) derived from the HRV power spectrum could detect shifts in autonomic balance in a setting with low sympathetic nervous tone. Healthy subjects were examined for 3 h in the supine position during 1) control conditions ( n = 12), 2) acute β-blockade ( n = 11), and 3) chronic β-blockade ( n = 10). Heart rate fell during the first 40 min of the control session (72 ± 2 to 64 ± 2 beats/min; P < 0.005) and was even lower during acute and chronic β-blockade (56 ± 2 beats/min; P < 0.005). The powers of all spectral areas rose during the first 60 min in all three settings, more so with β-blockade ( P < 0.05). LF/HF was found to contain the same information as powers expressed in normalized units. LF/HF detected the shift in autonomic balance induced by β-blockade but not the change induced by supine position. In conclusion, none of the investigated measures derived from power spectral analysis comprehensively and consistently described the changes in autonomic balance.

Beat‐to‐Beat QT Dynamics in Healthy Subjects

Background: Measures of QT dynamics express repolarization abnormalities that carry prognostic information, but the reproducibility of beat‐to‐beat QT dynamics has never been established. The QT interval is prolonged at night, but how the circadian rhythm and heart rate influence the dynamic QT measurements is still unsettled. The aims of the present study were: (1) to describe the reproducibility of beat‐to‐beat QT dynamics with respect to intrasubject, between‐subject, and between‐observer variability and (2) to describe the normal range, circadian variation, and heart rate dependence of QT dynamics.

Novel Donor Splice Site Mutation in the KVLQT1 Gene is Associated with Long QT Syndrome

KVLQT1 Gene Mutation and LQTS. Introduction: Inherited long QT syndrome (LQTS) recently has been associated with mutations in genes coding for potassium (KVLQTI, KCNEI, and HERG) or sodium (SCN5A) ion channels involved in regulating either sodium inward or potassium outward currents of heart cells, resulting in prolongation of the repolarization period. We describe a new mutation, a‐1 donor splice site mutation in a kindred with two affected members (QTc = 0.61 and 0.54 sec).

Reproducibility of heart rate variability, blood pressure variability and baroreceptor sensitivity during rest and head-up tilt

ObjectivePrevious studies have indicated moderate-to-poor reproducibility of heart rate variability (HRV) but the reproducibility of blood pressure variability (BPV) and spectral measures of baroreceptor sensitivity (BRS) are not well established. MethodsWe measured normal-to-normal heart beat (RR) interval and finger blood pressure (Finapres) in 14 healthy individuals on three different days. The protocol was 1 h of supine rest and 1 h of 60-degree head-up tilt. Time-series of consecutive 300-s segments as well as 1024-s segments of RR intervals and systolic, diastolic and mean blood pressures were extracted for the assessment of day-to-day and short-term reproducibility. Power spectrum analysis (Fourier) and transfer function analysis was performed. Reproducibility was assessed using the coefficient of variation (CV). The reproducibility of the mean RR interval, mean systolic, diastolic and mean blood pressure was good (CV<10 %). However, there was only moderate-to-poor reproducibility of the spectral parameters of HRV (CV range 18–36%) and BPV (16–44%) and moderate reproducibility of BRS (14–20%). ConclusionSpectral estimates of BRS had only moderate reproducibility although it was better than the spectral estimates of HRV and BPV.