Thomas Fetsch

Angiotensin II-Antagonist in Paroxysmal Atrial Fibrillation (ANTIPAF) Trial

Background— Unlike antiarrhythmic drugs, the safety and beneficial effects of angiotensin II receptor blockade (ARB) in patients with structural heart disease is well established. The clinical efficacy of ARBs to prevent atrial fibrillation (AF) so far only has been shown in patients with structural heart disease. Here, we report the primary outcome of the Angiotensin II-Antagonist in Paroxysmal Atrial Fibrillation (ANTIPAF) trial, which investigated the effect of olmesartan medoxomil compared with placebo on AF burden in patients with paroxysmal AF without structural heart disease. Methods and Results— The ANTIPAF trial was a prospective, randomized, placebo-controlled, multicenter trial analyzing the AF burden (percentage of days with documented episodes of paroxysmal AF) during a 12-month follow-up as the primary study end point. Four hundred thirty patients with documented paroxysmal AF without structural heart disease were randomized to placebo or 40 mg olmesartan per day. Concomitant therapy with ARBs, angiotensin-converting enzyme inhibitors, and antiarrhythmic drugs was prohibited. Patients were followed using daily transtelephonic ECG (tele-ECG) recordings independent of symptoms. The intention-to-treat population of the trial encompassed 425 patients (placebo group, n=211; olmesartan group, n=214). A total of 87 818 tele-ECGs were analyzed in these patients during follow-up (placebo group, 44 888 ECGs; olmesartan group, 42 930 ECGs). Thus, a mean of 207 tele-ECGs were recorded per patient. The primary end point (AF burden) was not different between the 2 groups (P=0.770). Secondary outcome parameters, including quality of life, also were not different. In particular, time to first AF recurrence, time to persistent AF, and number of hospitalizations were not different between the 2 groups. The time to prescription of recovery medication (amiodarone) was the only parameter showing an intergroup difference, with earlier prescription of amiodarone in the placebo group (P=0.022). Conclusions— One year of ARB therapy per se does not reduce the number of AF episodes in patients with documented paroxysmal AF without structural heart disease. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00098137.

Personalized management of atrial fibrillation: Proceedings from the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association consensus conference.

The management of atrial fibrillation (AF) has seen marked changes in past years, with the introduction of new oral anticoagulants, new antiarrhythmic drugs, and the emergence of catheter ablation as a common intervention for rhythm control. Furthermore, new technologies enhance our ability to detect AF. Most clinical management decisions in AF patients can be based on validated parameters that encompass type of presentation, clinical factors, electrocardiogram analysis, and cardiac imaging. Despite these advances, patients with AF are still at increased risk for death, stroke, heart failure, and hospitalizations. During the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association (AFNET/EHRA) consensus conference, we identified the following opportunities to personalize management of AF in a better manner with a view to improve outcomes by integrating atrial morphology and damage, brain imaging, information on genetic predisposition, systemic or local inflammation, and markers for cardiac strain. Each of these promising avenues requires validation in the context of existing risk factors in patients. More importantly, a new taxonomy of AF may be needed based on the pathophysiological type of AF to allow personalized management of AF to come to full fruition. Continued translational research efforts are needed to personalize management of this prevalent disease in a better manner. All the efforts are expected to improve the management of patients with AF based on personalized therapy.

Predictive Value of Wavelet Correlation Functions of Signal-Averaged Electrocardiogram in Patients After Anterior Versus Inferior Myocardial Infarction

OBJECTIVES This study sought to evaluate the prognostic value of wavelet correlation functions of the signal-averaged electrocardiogram (ECG) for arrhythmic events in patients after myocardial infarction. BACKGROUND Wavelet transform of the signal-averaged ECG has been shown to be a nonstationary analysis technique describing the time evolution of frequency spectra throughout the QRS complex. To quantify the wavelet transform, we introduced the new concept of the wavelet correlation function. METHODS The relation among wavelet correlation functions, ventricular late potentials and the site of infarction was investigated in 769 men < 66 years old who survived the acute phase of myocardial infarction (351 [46%] anterior, 418 [54%] inferior infarctions). Signal-averaged ECG recordings were obtained 2 to 3 weeks after infarction. During 6 months of follow-up, 33 patients (4.3%) experienced a malignant arrhythmic event. Wavelet correlation functions of the signal-averaged ECG were evaluated in a time-frequency plane ranging from 25 ms before QRS onset to 25 ms after QRS offset in the frequency range between 40 and 100 Hz. RESULTS Patients with an anterior infarction had lower mean wavelet correlation coefficients (p < 0.001) and a lower incidence of ventricular late potentials than patients with an inferior infarction (32.3% vs. 42.7%, p = 0.003). The combination of wavelet correlation functions and late potentials increased the total predictive accuracy from 52% to 72% for inferior and from 64% to 76% for anterior infarctions. CONCLUSIONS Spectral changes in the signal-averaged QRS complex are more prominent in anterior than inferior infarctions. Combination of late potential analysis and wavelet correlation functions increases the prognostic value for serious arrhythmic events after myocardial infarction.

Angiotensin II antagonist in paroxysmal atrial fibrillation (ANTIPAF) trial: rationale and study design.

Background and objective:Atrial fibrillation (AF) is the most common cardiac arrhythmia. Recent experimental data and retrospective analyses of clinical trials suggest that increased levels of angiotensin II can induce an arrhythmogenic atrial substrate, which favours the occurrence of AF.The purpose of the ANTIPAF (Angiotensin II Antagonist in Paroxysmal Atrial Fibrillation) trial is to prove the principal concept that blockade of angiotensin II type 1 receptors with olmesartan medoxomil 40 mg/day suppresses paroxysmal AF episodes during a 12-month follow-up. The ANTIPAF trial is the first placebo-controlled trial analysing the occurrence of AF as the primary study endpoint.Methods:Examination of the study hypothesis in a prospective, randomised, placebo-controlled, double-blind group comparison in patients with documented paroxysmal AF (total of 422 patients) stratified by β-adrenoceptor antagonist use. The primary endpoint of the study is the percentage of days with documented episodes of paroxysmal AF identified on daily transtelephonic tele-ECG recordings. Patients will record and transmit at least one 1-minute ECG per day independent of symptoms. Furthermore, tele-ECG recordings will be transmitted in any case of symptomatic AF. The present paper summarises the rationale and design of the ANTIPAF trial

Prediction of Arrhythmia Risk Based on Signal‐Averaged ECG in Postinfarction Patients

In patients surviving acute MI, identification of those at high risk for life‐threatening ventricular tachyarrhythmias and/or sudden death is of great importance. Numerous strategies based on indices such as the degree of left ventricular dysfunction, complex ventricular arrhythmias, or parameters of autonomic dysfunction have not yet led to an effective identification of the individual patient at risk. During the past decade, many investigators have recorded low amplitude, high frequency components in the terminal QRS complex (so‐called late potentials) from patients prone to sustained ventricular tachycardia. The SAECG has been used to predict life‐threatening tachyarrhythmias in patients after acute MI and to screen for inducible ventricular tachycardia in patients with unexplained syncope or sustained ventricular tachycardia. This review article describes the most frequently applied methodology and clinical applications of the SAECG in post‐MI patients and discusses the usefulness of noninvasive recordings in various other clinical settings.

Noninvasive Risk Modeling After Myocardial Infarction

The aim of this study was to extract and combine non-invasive risk parameters from the signal-averaged electrocardiogram (SAECG) and heart rate variability (HRV) based on 24-hour ambulatory electrocardiography to optimize the prognostic value for arrhythmic events after acute myocardial infarction. A prospective series of 553 men < 66 years of age enrolled in the Post-Infarction Late Potential study were analyzed. Within 2 to 4 weeks after acute myocardial infarction, all patients underwent SAECG and 24-hour ambulatory electrocardiography before hospital discharge. During 6 months of followup, 25 patients (4.5%) experienced arrhythmic events (sustained ventricular tachycardia, n = 11; ventricular fibrillation, n = 7; sudden cardiac death, n = 7). The predictive power of SAECG and HRV parameters was assessed using a Cox proportional-hazards model. In HRV analysis, the most significant differences between patients with and without arrhythmic events were observed for the beat-to-beat parameter root-meansquare of successive RR differences [RMSSD]): 25.7 +/- 16.9 ms in patients with arrhythmic events versus 34.1 +/- 18.6 ms in patients free of arrhythmic events (p = 0.004). Time domain analysis of the SAECG showed the QRS duration to be most significantly different in both patient groups: 106.4 +/- 18.7 ms (arrhythmic events) versus 95.3 +/- 18.7 ms (no arrhythmic events) (p = 0.001). Based on the Cox regression model, RMSSD and QRS duration were demonstrated to be independent significant risk factors (regression coefficient for QRS duration: cq = 0.014 +/- 0.006 ms(-1), p = 0.014; for RMSSD: cr = -0.041 +/- 0.016 ms(-1), p = 0.009). Based on the regression coefficients, an analytic risk model was developed describing the arrhythmic risk as a function of QRS duration, RMSSD, and time after infarction. We conclude that the combination of beat-to-beat changes of heart rate measured by RMSSD and QRS duration from the SAECG enhances noninvasive risk stratification after myocardial infarction.

Emergency coronary artery bypass grafting after failed coronary angioplasty: what has changed in a decade?

BACKGROUND We assessed the impact of patient and procedural characteristics on the outcome after emergency coronary artery bypass grafting (CABG) for failed percutaneous transluminal coronary angioplasty (PTCA) and temporal changes in these factors. METHODS Patients who underwent PTCA and subsequent emergency CABG were identified from the databases of the Departments of Cardiology and Cardiothoracic Surgery. RESULTS Two periods of clinical practice were compared. In 1989 to 1993, 2,880 PTCAs were performed, 64 patients underwent emergency CABG (2.3%), and 7 patients died (10.9%). During 1994 to 1998, 46 patients of 3,801 PTCAs underwent emergency CABG (1.2%, p < 0.01), and 7 patients died (15.2%, NS). The average rate of stenting increased from 0.8% to 24% in 1994 to 1998 as well as the frequency of arterial bypass grafts (0% vs 39%). In the latter period, patients were older, were more often females, had more cardiovascular risk factors, a higher Cleveland score (each p < 0.05), and suffered more often from periprocedural myocardial infarctions (p < 0.001) and nonfatal periprocedural complications (p < 0.01). CONCLUSIONS Although the frequency of emergency CABG after failed PTCA declined, perioperative mortality tended to increase according to an unfavorable shift in patient risk factors and morbidity.

Multiresolution decomposition of the signal-averaged ECG using the mallat approach for prediction of arrhythmic events after myocardial infarction

The aim of this study was to analyze the ability of the multiresolution decomposition of the signal-averaged electrocardiogram (ECG) to discriminate between patients who develop life-threatening ventricular arrhythmias after myocardial infarction and those who do not and to compare the predictive values of this approach with those obtained from the analysis of ventricular late potentials in the time domain. Signal-averaged ECGs of 769 prospectively included patients were analyzed. A total of 42 arrhythmic events occurred during the follow-up period. For numerical calculations of wavelet analysis, the total and relative energies of the QRS complex were obtained in seven frequency bands. The combination of the relative energy in the frequency bands 7.8-15.6 Hz and 62.5-125 Hz enhanced statistical performance as compared with the time-domain parameters (positive predictive accuracy, 11.3 vs 8.2%). Combining wavelet transform and time-domain parameters enhanced the predictive values even more (positive predictive accuracy, 14.3%) compared with applying each method alone.

Reduced Beat-to-Beat Changes of Heart Rate: An Important Risk Factor after Acute Myocardial Infarction

The prognostic significance of heart rate variability derived from 24-hour electrocardiographic recordings was investigated in 250 patients with acute myocardial infarction. During a follow-up of 6 months 15 patients experienced a serious arrhythmic event. These patients showed a significantly reduced beat to beat variability (p = 0.006), a slightly reduced 5-min variability (p = 0.04) and no significant differences in the 24-hour variability compared to the patients free of arrhythmic events. Based on Cox proportional hazard analysis, beat to beat variability remained an independent risk factor (p = 0.0036) in addition to the presence or absence of ventricular late potentials (p = 0.0004) and history of previous infarction (p = 0.04).

Apixaban in patients at risk of stroke undergoing atrial fibrillation ablation

Abstract Aims It is recommended to perform atrial fibrillation ablation with continuous anticoagulation. Continuous apixaban has not been tested. Methods and results We compared continuous apixaban (5 mg b.i.d.) to vitamin K antagonists (VKA, international normalized ratio 2–3) in atrial fibrillation patients at risk of stroke a prospective, open, multi-centre study with blinded outcome assessment. Primary outcome was a composite of death, stroke, or bleeding (Bleeding Academic Research Consortium 2–5). A high-resolution brain magnetic resonance imaging (MRI) sub-study quantified acute brain lesions. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) at baseline and at end of follow-up. Overall, 674 patients (median age 64 years, 33% female, 42% non-paroxysmal atrial fibrillation, 49 sites) were randomized; 633 received study drug and underwent ablation; 335 undertook MRI (25 sites, 323 analysable scans). The primary outcome was observed in 22/318 patients randomized to apixaban, and in 23/315 randomized to VKA {difference −0.38% [90% confidence interval (CI) −4.0%, 3.3%], non-inferiority P = 0.0002 at the pre-specified absolute margin of 0.075}, including 2 (0.3%) deaths, 2 (0.3%) strokes, and 24 (3.8%) ISTH major bleeds. Acute small brain lesions were found in a similar number of patients in each arm [apixaban 44/162 (27.2%); VKA 40/161 (24.8%); P = 0.64]. Cognitive function increased at the end of follow-up (median 1 MoCA unit; P = 0.005) without differences between study groups. Conclusions Continuous apixaban is safe and effective in patients undergoing atrial fibrillation ablation at risk of stroke with respect to bleeding, stroke, and cognitive function. Further research is needed to reduce ablation-related acute brain lesions.