Characteristics of patients with atrial fibrillation prescribed edoxaban in Belgium and the Netherlands: insights from the ETNA-AF-Europe study.

BACKGROUND: Studies on the use of non-vitamin K antagonist oral anticoagulants in unselected patients with atrial fibrillation (AF) show that clinical characteristics and dosing practices differ per region, but lack data on edoxaban. METHODS: With data from Edoxaban Treatment in routiNe clinical prActice for patients with AF in Europe (ETNA-AF-Europe), a large prospective observational study, we compared clinical characteristics (including the dose reduction criteria for edoxaban: creatinine clearance 15-50 ml/min, weight ≤60 kg, and/or use of strong p­glycoprotein inhibitors) of patients from Belgium and the Netherlands (BeNe) with those from other European countries (OEC). RESULTS: Of all 13,639 patients in ETNA-AF-Europe, 2579 were from BeNe. BeNe patients were younger than OEC patients (mean age: 72.3 vs 73.9 years), and had lower CHA2DS2-VASc (mean: 2.8 vs 3.2) and HAS-BLED scores (mean: 2.4 vs 2.6). Patients from BeNe less often had hypertension (61.6% vs 80.4%), and/or diabetes mellitus (17.3% vs 23.1%) than patients from OEC. Moreover, relatively fewer patients in BeNe were prescribed the reduced dose of 30 mg edoxaban (14.8%) than in OEC (25.4%). Overall, edoxaban was dosed according to label in 83.1% of patients. Yet, 30 mg edoxaban was prescribed in the absence of any dose reduction criteria in 36.9% of 30 mg users (5.5% of all patients) in BeNe compared with 35.5% (9.0% of all patients) in OEC. CONCLUSION: There were several notable differences between BeNe and OEC regarding clinical characteristics and dosing practices in patients prescribed edoxaban, which are relevant for the local implementation of dose evaluation and optimisation. TRIAL REGISTRATION: NCT02944019; Date of registration 24 October 2016.

Prognostic value of thrombolysis, coronary artery patency, signal-averaged electrocardiography, left ventricular ejection fraction, and Holter electrocardiographic monitoring for life-threatening ventricular arrhythmias after a first acute myocardial infarction.

Prognostic studies after acute myocardial infarction (AMI) have mainly been performed in the prethrombolytic era. Despite the fact that modern management of AMI has reduced mortality rates, the occurrence of malignant ventricular arrhythmias in the late phase of AMI remains an important issue. We prospectively studied 244 consecutive patients (97 treated with thrombolytics) who survived a first AMI. All patients underwent time domain signal-averaged electrocardiography (vector magnitude: measurements of total QRS duration, terminal low [<40 microV] amplitude signal duration, and root-mean-square voltage of the last 40 ms of the QRS complex), Holter electrocardiographic monitoring, and cardiac catheterization. Late life-threatening ventricular arrhythmias were recorded. Eighteen arrhythmic events occurred during a mean follow-up period of 57 +/- 18 months. Three independent factors were associated with a higher risk of arrhythmic events: (1) left ventricular ejection fraction (odds ratio 1.9/0.10 decrease), (2) terminal low-amplitude signal duration (odds ratio 1.5/5 ms increase), and (3) absence of thrombolytic therapy (odds ratio 3.9). Low-amplitude signal duration sensitivity for sudden cardiac death was low (30%). Left ventricular ejection fraction had the highest positive predictive value for sudden cardiac death (10%). Thus, thrombolysis decreases both the incidence of ventricular tachycardia and sudden cardiac death with a higher reopening rate of the infarct-related vessel. Signal averaging predicts the occurrence of ventricular tachycardia and an impaired left ventricular ejection fraction predicts the occurrence of sudden cardiac death.

Low energy internal cardioversion of atrial fibrillation resistant to transthoracic shocks.

OBJECTIVE: To investigate the efficacy of internal cardioversion using low energy shocks delivered with a biatrial electrode configuration in chronic atrial fibrillation resistant to transthoracic shocks. METHODS: Low energy internal cardioversion was attempted in 11 patients who had been in atrial fibrillation for 233 (SD 193) days and had failed to cardiovert with transthoracic shocks of 360 J in both apex-base and anterior-posterior positions. Synchronised biphasic shocks of up to 400 V (approximately 6 J) were delivered, usually with intravenous sedation only, between high surface area electrodes in the right atrium and the left atrium (coronary sinus in nine, left pulmonary artery in one, left atrium via patent foramen ovale in one). RESULTS: Sinus rhythm was restored in 8/11 patients. The mean leading edge voltage of successful shocks was 363 (46) V [4.9 (1.2) J]. Higher energy shocks induced transient bradycardia [time to first R wave 1955 (218) ms]. No proarrhythmia or other acute complications were observed. CONCLUSIONS: Low energy internal cardioversion of atrial fibrillation can restore sinus rhythm in patients in whom conventional transthoracic shocks have failed.

Effects of radiofrequency catheter ablation on patients with permanent pacemakers.

The objective of this study was to assess the effects of radiofrequency energy application on implanted pacemaker functions. Radiofrequency (RF) catheter ablation may cause pacemaker dysfunction due to electromagnetic interferences. The effects of RF on pacemaker behavior were studied in a series of 38 pacemakers, implanted 18 +/- 26 months prior to a RF procedure using either a right ventricular approach (AV node ablation, n = 35) or a left ventricular approach (left concealed accessory pathway ablation, n = 1; VT ablation, n = 2). The 38 patients (mean age 65 +/- 9 years) included 20 men and 18 women. Before energy applications, the 23 different pacemaker models were programmed to the VVI mode at the lowest available rate. The continuous surface ECG was recorded throughout the procedure. Thorough testing of the devices was performed before and after each RF delivery. Unusual pacemaker responses occurred in 20 of the 38 cases studied (53%). The impact of RF delivery was unpredictable, and variable dysfunctions were observed at different times for a given patient or could vary for a given model. Unusual pacemaker responses included pacemaker inhibition (n = 8), untoggled backup mode (n = 3), electromagnetic interference noise mode (n = 3), temporary RF-induced pacemaker tachycardia (n = 2), erratic behavior (n = 1), oversensing of RF onset and offset (n = 8), and transient loss of ventricular capture, (n = 1). Postablation, most devices automatically toggled back to full functionality. The three devices in the untoggled backup mode had to be reprogrammed to obtain normal operations. At the end of the procedure, pacing thresholds remained unchanged in all but one patient, in whom the increase in ventricular threshold was due to a nicked lead. In conclusion, implanted pacemakers frequently exhibit transient, unpredictable responses to RF energy application. Although all pacemaker functions were restored postablation, some devices had to be reset manually. The anomalies observed during the RF application argue for the simultaneous use of an external pacemaker in pacing-dependent patients.

[Risk of mortality after myocardial infarction: value of heart rate, its variability and left ventricular ejection fraction]. / Risque de mortalité après un infarctus du myocarde: apport de la fréquence cardiaque, de sa variabilité, et de la fraction d'éjection ventriculaire gauche.

Heart rate variability is a useful parameter for risk stratification after myocardial infarction. However, the relationship between heart rate itself and its variability has not been adequately studied. The authors compared the average RR interval of 24 hours recorded by Holter monitoring with the variability of heart rate and of left ventricular ejection fraction to assess the risk of death after myocardial infarction. A total of 579 patients was followed up for 2 years after acute myocardial infarction. During this period, there were 54 deaths, 42 of cardiac origin, 26 being classified as sudden death. The positive predictive value of left ventricular ejection fraction was lower than those of mean RR interval and the variability of heart rate for overall mortality, cardiac mortality and sudden death. The three indices were essentially equivalent for the prediction of non-sudden cardiac death. The positive predictive value of heart rate variability was better than the mean RR interval for sensitivities < 40%, for all cause mortality. However, for sensitivities > 40%, the two parameters were equivalent or slightly in favour of the mean heart rate over 24 hours. The authors conclude that the mean RR interval over 24 hours is an important prognostic index after myocardial infarction. This index is more powerful than left ventricular ejection fraction and comparable to heart rate variability.

[Influence of the duration of recording in the reproducibility of the signal averaged electrocardiogram]. / Influence de la durée de l'enregistrement sur la reproductibilité de l'électrocardiogramme à haute amplification.

The authors studied the possibility of improving the reproducibility of the signal averaged ECG by increasing the number of averaged QRS complexes. One hundred patients were included in the study. In each cases, 400 QRS complexes were recorded on twice, consecutively, in strictly identical conditions. During each recording, the total duration of the amplified and averaged QRS complex (tQRS), the duration of the terminal signal below 40 microV (LAS) and the root mean square of the amplitude of the last 40 ms (RMS) were determined for 100, 200, 300 and 400 recorded QRS complexes. The presence of late potentials was defined as the positivity of two of the following criteria: tQRS > 114 ms, LAS > 38 ms, RMS < 20 microV. The number of contradictory diagnostic conclusions between two successive recordings of the same duration decreased progressively with the number of averaged QRS complexes: 10 for 100 QRS, 10 for 200 QRS, 9 for 300 QRS and 6 for 400 QRS complexes, but this improvement was not statistically significant. The absolute differences of tQRS and RMS between two successive recordings of the same duration were statistically different for the four durations of recording (p = 0.05) and there was a tendency towards statistical significance for LAS (p = 0.09). The best quantitative reproducibility of the 3 parameters was obtained with the recording of 300 QRS complexes. In conclusion, the reproducibility of the signal averaged ECG is improved when the number of average QRS complexes is increased. The authors' results suggests that reproducibility this is optimal with the amplification and averaging of 300 QRS complexes.

[Reproducibility of signal-averaged electrocardiography]. / Reproductibilité immédiate de l'électrocardiogramme à haute amplification et moyennage.

The reproducibility of the parameters defining the presence of late potentials on the signal-averaged electrocardiogram is one of the limiting factors of the method. The authors studied the coefficients of correlation and reproducibility of these parameters in patients with coronary artery disease. In addition, they tried to determine which parameter was most often responsible for changing a diagnostic conclusion (i.e., presence or absence of late potentials). Two signal-averaged ECGs were recorded one after the other in 127 patients. The presence of late potentials was defined as the presence of a least two of the following criteria: total amplified and averaged QRS duration (tQRS) > 114 ms: duration of the last signal of under 40 microV (LAS) > 38 ms, and root mean square of the amplitude of the last 40 ms (RMS) < 20 microV. The correlation coefficients were 0.98, 0.96 and 0.94 for the duration of tQRS, LAS and RMS respectively (p < 0.0001). The coefficients of reproducibility were 7.0 ms. 7.0 ms and 16.1 microV respectively. Late potentials were present in 22% of patients. A change in diagnosis between the first and second recording was observed in 10 subjects (8% of the population). A combined change in LAS and RMS was responsible for 6 of these revised diagnoses, a change in LAS alone in 2 cases, of the RMS alone in 1 case and the tQRS alone in 1 case. In patients with coronary artery disease, the immediate reproducibility of the diagnosis of late potentials is affected by changes in LAS and RMS. The tQRS is only rarely responsible for a change in diagnosis. This study suggests that the result of the signal-averaged ECG should be interpreted with caution when the LAS or RMS are near their threshold values.

[Activity of the sympathetic nervous system and of the renin-angiotensin system in the acute stage of myocardial infarction]. / Etude de l'activité des systèmes sympathique et rénine-angiotensine à la phase aiguë de l'infarctus myocardique.

We studied sympathetic and renin-angiotensin systems activity in a series of 175 patients suffering from acute myocardial infarction. These two systems were both overactivated especially in the cases complicated by hemodynamically documented left heart failure. The response of these systems to acute heart failure was in the same range for patients younger or older than 65 years and the witness (norepinephrine and plasma renin levels) of sympathetic and renin-angiotensin activities were good independent prognostic factors of in-hospital mortality.

Mianserin and ventricular tachycardia: case report and review of the literature.

Mianserin is a drug frequently used to treat depression and sleep disturbances. Despite documented effects on various cardiac tissues in animal studies, mianserin has a very safe clinical profile. Only one case of ventricular arrhythmias in a patient treated with mianserin has been reported. This patient had a severe cardiac history. Our case is to our knowledge the first report on ventricular arrhythmias in a patient treated with mianserin without previous or present cardiac disease. After discontinuation of mianserin the arrhythmias disappeared within days. The literature on mianserin toxicity is reviewed.

Identification of atrial fibrillation episodes in ambulatory electrocardiographic recordings: validation of a method for obtaining labeled R-R interval files.

Current systems for analyzing ambulatory electrocardiograms (ECGs) are unable to distinguish precisely between sinus rhythm and atrial fibrillation (AF) episodes, and are unable to produce RR interval listings that distinguish AF from sinus rhythm on a beat-to-beat basis. We describe a method for obtaining such a computerized listing ("Composite Rhythm" file) from ambulatory recordings containing episodes of AF. The file lists the rhythm of each beat, its real time, and the QRS complex morphology. A visual inspection is made of a full printout of the recording to identify the precise time of onset and termination of each episode of AF. These times are entered into a computer and identified with the corresponding beats on a conventional RR interval file generated by Holter analysis. The method was validated using 1-hour segments from 20 ambulatory ECGs containing 145 episodes of AF. These were visually identified by four independent observers with a mean sensitivity of 99.1%. The first beat of AF was identified concordantly in 96% of episodes, with a discrepancy of < or = 3 beats in the other episodes. The times of 200 selected QRS complexes were then entered into the computer by each observer; 91.1% of these complexes were identified exactly and 100% were identified to within one beat. The Composite Rhythm files have several potential applications for testing AF detection algorithms and studying the mode of onset of AF.

Accuracy and limitations of published algorithms using the twelve-lead electrocardiogram to localize overt atrioventricular accessory pathways.

INTRODUCTION: The purpose of this study was to evaluate the accuracy and limitations of published algorithms using the 12-lead ECG to localize AV accessory pathways (APs). METHODS AND RESULTS: The 11 relevant algorithms found in the literature (MEDLINE database and major scientific sessions) were tested on a series of 266 consecutive patients who successfully underwent radiofrequency catheter ablation of a single overt AV AP. The positive predictive values (PPV) of the algorithms in applicable patients were significantly lower for algorithms with > 6 accessory location sites (40.6% +/- 10.9% vs 61.2% +/- 8.0%; P < 0.03) and show a tendency for algorithms not relying on delta wave polarity but on QRS polarity only (36.6% +/- 11.2% vs 52.3% +/- 13.1%; P = 0.09). The PPV in applicable patients is related to the AP location (P < 0.001) and ranked from the highest to the lowest as follows: left lateral (mean PPV = 86.3%), posteroseptal (mean PPV = 65.2%), right anteroseptal (mean PPV = 45.2%), and right posterolateral (mean PPV = 23.4%). CONCLUSION: Our study suggests that the accuracy of algorithms relying on the 12-lead ECG depends on AP locations as defined in the algorithms and on the number of AP sites. The accuracy tends to be lower when delta wave polarity is not included in the algorithm's architecture. This should be considered when using these algorithms or when building new ones.