The changing circumstance of atrial fibrillation - progress towards precision medicine.

The prevalence of atrial fibrillation (AF) in the general population is between 1% and 2% in the developed world and is higher in men than in women. The arrhythmia occurs much more commonly in the elderly, and the estimated lifetime risk of developing AF is one in four for men and women aged 40 years and above. Projected data from multiple population-based studies in the USA and Europe predict a two- to threefold increase in the number of AF patients by 2060. The high lifetime risk of AF and increased longevity underscore the important public health burden posed by this arrhythmia worldwide. AF has multiple aetiologies and a broad variety of presentations. The primary pathologies underlying or promoting the occurrence of AF vary more than for any other cardiac arrhythmia, ranging from autonomic imbalance to organic heart disease and metabolic disorders, such as diabetes mellitus, metabolic syndrome, hyperthyroidism and kidney disease, and lifestyle factors such as smoking, alcohol consumption and participation in endurance sports. Biomarkers are increasingly being investigated and, together with clinical and genetic factors, will eventually lead to a clinically valuable detailed classification of AF which will also incorporate pathophysiological determinants and mechanisms of the arrhythmia. In turn, this will allow the development and application of precision medicine to this troublesome arrhythmia.

Edoxaban vs. warfarin in patients with atrial fibrillation on amiodarone: a subgroup analysis of the ENGAGE AF-TIMI 48 trial.

BACKGROUND: In the ENGAGE AF-TIMI 48 trial, the higher-dose edoxaban (HDE) regimen had a similar incidence of ischaemic stroke compared with warfarin, whereas a higher incidence was observed with the lower-dose regimen (LDE). Amiodarone increases edoxaban plasma levels via P-glycoprotein inhibition. The current pre-specified exploratory analysis was performed to determine the effect of amiodarone on the relative efficacy and safety profile of edoxaban. METHODS AND RESULTS: At randomization, 2492 patients (11.8%) were receiving amiodarone. The primary efficacy endpoint of stroke or systemic embolic event was significantly lower with LDE compared with warfarin in amiodarone treated patients vs. patients not on amiodarone (hazard ratio [HR] 0.60, 95% confidence intervals [CIs] 0.36-0.99 and HR 1.20, 95% CI 1.03-1.40, respectively; P interaction <0.01). In patients randomized to HDE, no such interaction for efficacy was observed (HR 0.73, 95% CI 0.46-1.17 vs. HR 0.89, 95% CI 0.75-1.05, P interaction = 0.446). Major bleeding was similar in patients on LDE (HR 0.35, 95% CI 0.21-0.59 vs. HR 0.53, 95% CI 0.46-0.61, P interaction = 0.131) and HDE (HR 0.94, 95% CI 0.65-1.38 vs. HR 0.79, 95% CI 0.69-0.90, P interaction = 0.392) when compared with warfarin, independent of amiodarone use. CONCLUSIONS: Patients randomized to the LDE treated with amiodarone at the time of randomization demonstrated a significant reduction in ischaemic events vs. warfarin when compared with those not on amiodarone, while preserving a favourable bleeding profile. In contrast, amiodarone had no effect on the relative efficacy and safety of HDE.

Atrial fibrillation in the military patient: a review.

Atrial fibrillation (AF) is the most common sustained atrial arrhythmia, and increases an individual's risk of morbidity and mortality from cardiovascular and thromboembolic events. In this article, we review the pathophysiology and clinical presentations of AF and describe appropriate investigations and management likely to be appropriate for a military population, in line with current National Institute for Health and Care Excellence and European Society of Cardiology guidelines. The implications for the individual's Medical Employment Standard in the UK Armed Forces, with specific reference to specific military occupational activities such as aviation, diving and driving occupationally, are also reviewed.

Novel oral anticoagulants and stroke prevention in atrial fibrillation and chronic heart failure.

Heart failure (HF) and atrial fibrillation (AF) frequently coexist and share a reciprocal relationship. The presence of AF increases the propensity to HF and can worsen its severity as well as escalating the risk of stroke. Despite the proven efficacy of vitamin K antagonists and warfarin for stroke prevention in AF, their use is beset by numerous problems. These include their slow onset and offset of action, unpredictability of response, the need for frequent coagulant monitoring and serious concerns around the increased risks of intracranial and major bleeding. Three recently approved novel anticoagulants (dabigatran, rivaroxaban and apixaban) are already challenging warfarin use in AF. They have a predictable therapeutic response and a wide therapeutic range and do not necessitate coagulation monitoring. In this article, the relationship between HF and AF and the mechanisms for their compounded stroke risk are reviewed. The evidence to support the use of these three NOACs amongst patients with AF and HF is further explored.

Ischaemic stroke prevention in patients with atrial fibrillation and high bleeding risk: opportunities and challenges for percutaneous left atrial appendage occlusion.

Patients with atrial fibrillation (AF) are at an increased risk of ischaemic stroke. The efficacy of stroke prevention with vitamin K antagonists in these patients has been well established. However, associated bleeding risks may offset the therapeutic benefits in patients with risk factors for bleeding. Despite improvements achieved by novel oral anticoagulants, bleeding remains a clinically relevant problem, especially gastrointestinal bleeding. Percutaneous occlusion of the left atrial appendage (LAA) may be considered as an alternative stroke prevention therapy in AF patients with a high bleeding risk. This paper explores patient groups in whom oral anticoagulation may be challenging and percutaneous LAA occlusion (LAAO) has a potentially better risk-benefit balance. The current status of LAAO and future directions are reviewed, and particular challenges for LAA occlusion requiring further clinical data are discussed. This article is a summary of the Third Global Summit on LAA occlusion, 15 March 2013, Barcelona, Spain.

State of play and future direction with NOACs: An expert consensus.

Atrial fibrillation (AF) and venous thromboembolism (VTE) are cardiovascular conditions significant in contemporary practice. In both, the use of anticoagulation with vitamin K antagonists (VKAs) has been traditionally used to prevent adverse events. However, VKA therapy is associated with challenges relating to dose maintenance, the need to monitor anticoagulation, and bleeding risks. The non-vitamin K oral anticoagulants (NOACs) are becoming accepted as a clear alternative to VKA therapy for both AF and VTE management. The aim of this paper was to review contemporary evidence on the safety of NOACs in both conditions. A comprehensive literature review was conducted to explore key safety issues and expert consensus was achieved from eight professionals specialised in AF and VTE care. Consensus-based statements were formulated where available evidence was weak or contradictory. The expert statements in this paper form a key overview of the safety of NOACs compared with VKA therapy, and the comparative safety of different NOACs. It is apparent that a detailed patient work-up is required in order to identify and manage individual risk factors for bleeding and thrombosis prior to NOAC therapy. Additional measures, such as dose reductions, may also be used to maintain the safety of NOACs in practice.

Conventional and dedicated atrial overdrive pacing for the prevention of paroxysmal atrial fibrillation: the AFTherapy study.

AIMS: This investigation was conducted to determine the effectiveness of several conventional overdrive pacing modalities (single rate and rate responsive pacing at various lower rates) and of four dedicated preventive pacing algorithms in the suppression of paroxysmal atrial fibrillation (AF). METHOD AND RESULTS: In this multi-centre, randomized trial, 372 patients with drug-refractory paroxysmal AF were enrolled. Patients received a dual-chamber pacing device capable of delivering conventional pacing therapy as well as dedicated AF prevention pacing therapies and to record detailed AF-related diagnostics. The primary endpoint was AF burden, whereas secondary endpoints were time to first AF episode and averaged sinus rhythm duration. During a conventional pacing phase, patients were randomized to single rate or rate-responsive pacing with lower rates of either 70 or 85 min(-1) or to a control group with single rate pacing at 40 min(-1). In the subsequent preventive pacing phase, patients underwent pacing at a lower rate of 70 min(-1) with or without concomitant application of four preventive pacing algorithms. A substantial amount of data was excluded from the analysis because of atrial-sensing artefacts, identified in the device-captured diagnostics. In the conventional pacing phase, no significant differences were found between various lower rates and the control group receiving single rate pacing at 40 min(-1) or between single rate and rate-responsive pacing. Patients receiving preventive pacing with all four therapies enabled had a similar AF burden compared with patients treated with conventional pacing at 70 min(-1) (P = 0.47). CONCLUSIONS: The results do not demonstrate a significant effect of conventional atrial overdrive pacing or preventive pacing therapies. However, the observations provided important information for further consideration with respect to the design and conduct of future studies on the effect of atrial pacing therapies for the reduction of AF.

Double-blind placebo-controlled trial of digoxin in symptomatic paroxysmal atrial fibrillation.

BACKGROUND: Digoxin is commonly prescribed in symptomatic paroxysmal atrial fibrillation (AF) but has never been evaluated in this condition. METHODS AND RESULTS: From a multicenter registry, 43 representative patients with frequent symptomatic AF episodes were recruited into a randomized, double-blind crossover comparison of digoxin (serum concentration, 1.29+/-0.35 nmol/L) and placebo. The study end point was the occurrence of 2 AF episodes (documented by patient-activated monitors), censored at 61 days. The median time to 2 episodes was 13.5 days on placebo and 18.7 days on digoxin (P<0. 05). The relative risk (95% CI) of 2 episodes (placebo:digoxin) was 2.19 (1.07 to 4.50). A similar effect was seen on the median time to 1 episode: increased from 3.5 to 5.4 days (P<0.05), relative risk 1. 69 (0.88 to 3.24). The mean+/-SD ventricular rates during AF recordings during placebo and digoxin treatment were 138+/-32 and 125+/-35 bpm, respectively (P<0.01). Twenty-four-hour ambulatory ECG recordings did not show significant differences in the frequency or duration of AF or in ventricular rate. CONCLUSIONS: Digoxin reduces the frequency of symptomatic AF episodes. However, the estimated effect is small and may be due to a reduction in the ventricular rate or irregularity rather than an antiarrhythmic action.

Amiodarone interaction with beta-blockers: analysis of the merged EMIAT (European Myocardial Infarct Amiodarone Trial) and CAMIAT (Canadian Amiodarone Myocardial Infarction Trial) databases. The EMIAT and CAMIAT Investigators.

BACKGROUND: Investigations with in vitro and animal models suggest an interaction between amiodarone and beta-blockers. The objective of this work was to explore if an interaction with beta-blocker treatment plays a role in the decrease of cardiac arrhythmic deaths with amiodarone in patients recovered from an acute myocardial infarction. METHODS AND RESULTS: A pooled database from 2 similar randomized clinical trials, the European Amiodarone Myocardial Infarction Trial (EMIAT) and the Canadian Amiodarone Myocardial Infarction Trial (CAMIAT), was used. Four groups of post-myocardial infarction patients were defined: beta-blockers and amiodarone used, beta-blockers used alone, amiodarone used alone, and neither used. All analyses were done on an intention-to-treat basis. Unadjusted and adjusted relative risks for all-cause mortality, cardiac death, arrhythmic cardiac death, nonarrhythmic cardiac death, arrhythmic death, or resuscitated cardiac arrest were lower for patients receiving beta-blockers and amiodarone than for those without beta-blockers, with or without amiodarone. The interaction was statistically significant for cardiac death and arrhythmic death or resuscitated cardiac arrest (P=0.05 and 0.03, respectively). Findings were consistent across subgroups. CONCLUSIONS: These findings are based on a post hoc analysis. However, they confirm prior results from in vitro and animal experiments suggesting an interaction between beta-blockers and amiodarone. In practice, not only is the adjunct of amiodarone to beta-blockers not hazardous, but beta-blocker therapy should be continued if possible in patients in whom amiodarone is indicated.

Geometrically accurate transaortic mapping of left ventricular endocardial activation during surgery.

A device was developed for mapping left ventricular endocardial activation through the aortic valve during surgery. It uses an exploring electrode at the tip of a hand-held probe that is mounted on a mechanical arm with six joints whose movements are digitized by a computer while the position of the probe tip is calculated continuously. The probe is inserted by the surgeon into the left ventricle retrogradely through the aortic valve after the patient is on total cardiopulmonary bypass, the aorta has been opened and the coronary arteries cannulated. The electrode position relative to the aortic valve and left ventricular apex is displayed continuously on a computer screen. When electrograms are recorded from the probe, their positions are displayed on the screen relative to a stylized grid of the left ventricular endocardial surface and are color-coded to indicate the activation sequence. In a patient with nonischemic ventricular tachycardia, the arrhythmia was successfully mapped and cryoablated with use of the device. The device will be developed so that a cryoprobe can be substituted for the exploring electrode and positioned at the source of activation determined by the map.

Distinction between arrhythmic and nonarrhythmic death after acute myocardial infarction based on heart rate variability, signal-averaged electrocardiogram, ventricular arrhythmias and left ventricular ejection fraction.

OBJECTIVES: We investigated whether heart rate variability, the signal-averaged electrocardiogram (ECG), ventricular arrhythmias and left ventricular ejection fraction predict the mechanism of cardiac death after myocardial infarction. BACKGROUND: Postinfarction risk stratification studies have almost exclusively focused on predicting the risk of arrhythmic death. The factors that identify and distinguish persons at risk for arrhythmic and nonarrhythmic death are poorly known. METHODS: Heart rate variability, the signal-averaged ECG, ventricular arrhythmias and left ventricular ejection fraction were assessed in 575 survivors of acute myocardial infarction. The patients were followed up for 2 years; arrhythmic and nonarrhythmic cardiac deaths were used as clinical end points. During the follow-up period, 47 cardiac deaths occurred, 29 (62%) arrhythmic and 18 (38%) nonarrhythmic. RESULTS: All risk factors were associated with cardiac mortality in univariate analysis. With the exception of left ventricular ejection fraction, they were also predictors of arrhythmic death. Depressed heart rate variability (p < 0.001), ventricular ectopic beats (p < 0.001) and low ejection fraction (p < 0.001) were related to nonarrhythmic death. In multivariate analysis, depressed heart rate variability (p < 0.001) and runs of ventricular tachycardia (p < 0.05) predicted arrhythmic death. Nonarrhythmic death was associated with depressed heart rate variability (p < 0.001), ventricular ectopic beats (p < 0.001) and low ejection fraction (p < 0.01). By selecting patients with depressed heart rate variability, long filtered QRS duration or ventricular arrhythmias and excluding patients with the lowest ejection fraction, we identified a group in which 75% of deaths were arrhythmic. Similarly, by selecting patients with a low ejection fraction and excluding patients with the lowest heart rate variability, we identified a group in which 75% of deaths were nonarrhythmic. CONCLUSIONS: Arrhythmic death was associated predominantly with depressed heart rate variability and ventricular tachycardia runs, and nonarrhythmic death with low ejection fraction, ventricular ectopic beats and depressed heart rate variability. A combination of risk factors identified patient groups in which a majority of deaths were either arrhythmic or nonarrhythmic.

Inducibility of sustained monomorphic ventricular tachycardia as a prognostic indicator in survivors of recent myocardial infarction: a prospective evaluation in relation to other prognostic variables.

The prognostic significance of sustained monomorphic ventricular tachycardia inducible with up to three extrastimuli was assessed in relation to other prognostic markers, including clinical assessment, signal-average electrocardiogram (ECG), Holter monitoring, ejection fraction measurement and exercise testing, in 75 patients after recent myocardial infarction. Among eight patients with inducible sustained monomorphic ventricular tachycardia, six suffered arrhythmic events during a median follow-up period of 16 months. No patient without inducible sustained monomorphic ventricular tachycardia suffered an arrhythmic event. Multivariate analysis showed that of all the variables examined, inducible sustained monomorphic ventricular tachycardia was the only independent predictor of arrhythmic events during the follow-up period. The sensitivity for predicting arrhythmic events by this response was 100%, the specificity 97% and the positive predictive accuracy 75%. Individually, the other prognostic variables were less sensitive and much less accurate predictors of arrhythmic events, but the combination of the occurrence of acute phase complications or frequent ectopic activity with an abnormal signal-averaged ECG approached the sensitivity and accuracy of inducible sustained monomorphic ventricular tachycardia. The prognostic utility of programmed ventricular stimulation in patients with recent myocardial infarction is limited because comparable information can be obtained less invasively. However, the test may have a role in selecting therapy in patients judged to be at risk from arrhythmias on the basis of noninvasive assessment.

Assessment of autonomic function in patients with neurally mediated syncope: augmented cardiopulmonary baroreceptor responses to graded orthostatic stress.

OBJECTIVES: The purpose of this study was to assess vagal tone and cardiopulmonary baroreceptor activity in patients with tilt-induced neurally mediated syncope. BACKGROUND: The causes of individual susceptibility to orthostatic stress leading to recurrent neurally mediated syncope remain obscure. The trigger for sympathetic withdrawal and increased vagal activity is believed to be stimulation of ventricular mechanoreceptors. METHODS: Seventeen patients (mean age 50.6 years) with recurrent syncope and a positive response on a 45-min 60 degrees head-up tilt test were compared with a control group of 17 patients (mean age 47.5 years) with unexplained syncope and negative tilt test findings. Vagal activity was assessed by high pressure baroreceptor testing and by temporal and spectral analysis of heart rate variability during Holter ambulatory electrocardiographic monitoring. Cardiopulmonary baroreceptor sensitivity was assessed by measurement of forearm vascular responses to lower body negative pressure. RESULTS: Mean high pressure baroreceptor sensitivity was 16.4 +/- 12.2 ms/mm Hg in the group with a positive tilt test response compared with 15.1 +/- 13.0 ms/mm Hg in the control group (p = NS). There were no significant differences between the groups in any of the temporal or spectral measures of heart rate variability. The increase in forearm vascular resistance in response to lower body negative pressure was 11.5 +/- 14.2 U in patients with tilt-induced syncope and 3.5 +/- 3.2 U in the control group at -5 mm Hg, 16.8 +/- 18.6 U and 4.8 +/- 5.3 U, respectively, at -10 mm Hg and 26.4 +/- 24.3 U and 10.2 +/- 7.8 U, respectively, at -20 mm Hg (p < 0.001). CONCLUSIONS: Patients with tilt-induced neurally mediated syncope have augmented cardiopulmonary baroreceptor responses to orthostatic stress. This finding sheds new light on the etiology of neurally mediated syncope.

Efficacy and tolerability of transvenous low energy cardioversion of paroxysmal atrial fibrillation in humans.

OBJECTIVES: This study investigated the efficacy and tolerability of low energy shocks for termination of atrial fibrillation in patients, using an endocardial electrode configuration that embraced both atria. BACKGROUND: In animals, low energy biphasic shocks delivered between electrodes in the coronary sinus and right atrium have effectively terminated atrial fibrillation. If human defibrillation thresholds are sufficiently low, atrial defibrillation could be achieved in conscious patients using an implanted device. METHODS: Twenty-two consecutive patients with stable atrial fibrillation were studied during electrophysiologic testing. Biphasic R wave synchronous shocks were delivered between large surface area electrodes in the coronary sinus and high right atrium, using a step-up voltage protocol starting at 10 or 20 V and increasing to a maximum of 400 V. Patients were conscious at the start of the study and were asked to report on symptoms but were sedated later if shocks were not tolerated. RESULTS: Cardioversion was achieved in all 19 patients who completed the study, with a mean (+/- SD) leading-edge voltage of 237 +/- 55 V (range 140 to 340) and mean energy of 2.16 +/- 1.02 J (range 0.7 to 4.4). The mean maximal shock delivered without sedation was 116 +/- 51 V (range 60 to 180). No proarrhythmia or mechanical complications occurred. CONCLUSIONS: The delivery of biphasic R wave synchronous shocks between the high right atrium and coronary sinus can terminate atrial fibrillation with very low energies. General anaesthesia is not required, and a minority of fully conscious patients are able to tolerate this method of cardioversion.

Predictive power of increased heart rate versus depressed left ventricular ejection fraction and heart rate variability for risk stratification after myocardial infarction. Results of a two-year follow-up study.

OBJECTIVES: The aim of this study was to compare the predictive value of mean RR interval assessed from predischarge Holter recordings with that of heart rate variability and left ventricular ejection fraction for risk stratification after myocardial infarction. BACKGROUND: Heart rate variability is a powerful tool for risk stratification after myocardial infarction. Although heart rate variability is related to heart rate, little is known of the prognostic value of 24-h mean heart rate. METHODS: A total of 579 patients surviving the acute phase of myocardial infarction were followed up for at least 2 years. Predischarge heart rate variability, 24-h mean RR interval and left ventricular ejection fraction were analyzed. RESULTS: During the first 2 years of follow-up, there were 54 deaths, 42 of which were cardiac (26 sudden). Shorter mean RR interval was a better predictor of all-cause mortality as well as cardiac and sudden death than depressed left ventricular ejection fraction. Depressed heart rate variability predicted the risk of death better than mean RR interval for sensitivities < 40%. For sensitivities > or = 40%, mean RR interval was as powerful as heart rate variability. All three variables performed equally well in predicting nonsudden cardiac death. For cardiac death prediction, a left ventricular ejection fraction < 35% had a 40% sensitivity, 78% specificity and 14% positive predictive accuracy; a mean RR interval < 700 ms had a 45% sensitivity, 85% specificity and 20% positive predictive accuracy; and a heart rate variability < 17 U had a 40% sensitivity, 86% specificity and 20% positive predictive accuracy. CONCLUSIONS: Predischarge 24-h mean heart rate is a strong predictor of mortality after myocardial infarction that can compete with left ventricular ejection fraction and heart rate variability.

Radiofrequency current delivery by way of a bipolar tricuspid annulus-mitral annulus electrode configuration for ablation of posteroseptal accessory pathways.

OBJECTIVES: This report describes a novel technique for ablation of "difficult" posteroseptal pathways. BACKGROUND: Although radiofrequency ablation of accessory atrioventricular (AV) pathways is successful in > or = 90% of cases, particular difficulty may be encountered with some bypass tracts in the posteroseptal region. METHODS: In eight patients with posteroseptal accessory pathways (two concealed), radiofrequency catheter ablation using conventional unipolar current applications from favorable sites along the tricuspid or mitral annulus, or both, was unsuccessful. Subsequently, a bipolar technique was adopted, with current application between the distal electrodes of two catheters positioned against the septal region at sites of early activation along both mitral and tricuspid annuli. RESULTS: The bipolar configuration proved effective in all cases. The number of bipolar lesions required for success was one (five patients), five (two patients) and nine (one patient). In five patients, bipolar current application abolished pathway conduction using positions at which delivery of unipolar lesions had been ineffective or caused transient block. The AV or ventriculoatrial interval at successful sites varied from 20 to 65 ms, and the time from delta wave onset to local ventricular activation was zero or negative. There were no complications attributable to the bipolar technique. During follow-up of 8 to 36 weeks, pathway conduction has not recurred in any patient. CONCLUSIONS: Bipolar radiofrequency current delivery across the septal region using a tricuspid annulus-mitral annulus electrode configuration may abolish accessory pathway conduction when conventional unipolar applications have proved ineffective. The technique may reduce procedure duration, radiation exposure and overall failure rate in these problematic cases.

Is there increased sympathetic activity in patients with hypertrophic cardiomyopathy?

OBJECTIVES: This study aimed to assess autonomic nervous system activity in patients with hypertrophic cardiomyopathy. BACKGROUND: Patients with hypertrophic cardiomyopathy are traditionally thought to have increased sympathetic activity. However, convincing evidence is lacking. METHODS: Heart rate variability was assessed from 24-h ambulatory electrocardiographic (Holter) recordings in 31 patients with hypertrophic cardiomyopathy and 31 age- and gender-matched normal control subjects in a drug-free state. Spectral heart rate variability was calculated as total (0.01 to 1.00 Hz), low (0.04 to 0.15 Hz) and high (0.15 to 0.40 Hz) frequency components using fast Fourier transformation analysis. RESULTS: There was a nonsignificant decrease in the total frequency component of heart rate variability in patients with hypertrophic cardiomyopathy compared with that of normal subjects (mean +/- SD 7.24 +/- 0.88 versus 7.59 +/- 0.57 ln[ms2], p = 0.072). Although there was no significant difference in the high frequency component (5.31 +/- 1.14 versus 5.40 +/- 0.91 ln[ms2], p = 0.730), the low frequency component was significantly lower in patients than in normal subjects (6.25 +/- 1.00 versus 6.72 +/- 0.61 ln[ms2], p = 0.026). After normalization (i.e., division by the total frequency component values), the low frequency component was significantly decreased (38 +/- 8% versus 43 +/- 8%, p = 0.018) and the high frequency component significantly increased (16 +/- 6% versus 12 +/- 6%, p = 0.030) in patients with hypertrophic cardiomyopathy. The low/high frequency component ratio was significantly lower in these patients (0.94 +/- 0.64 versus 1.33 +/- 0.55, p = 0.013). In patients with hypertrophic cardiomyopathy, heart rate variability was significantly related to left ventricular end-systolic dimension and left atrial dimension but not to maximal left ventricular wall thickness. No significant difference in heart rate variability was found between 14 victims of sudden cardiac death and 10 age- and gender-matched low risk patients. CONCLUSIONS: Our observations suggest that during normal daily activities, patients with hypertrophic cardiomyopathy experience a significant autonomic alteration with decreased sympathetic tone.

Depressed heart rate variability identifies postinfarction patients who might benefit from prophylactic treatment with amiodarone: a substudy of EMIAT (The European Myocardial Infarct Amiodarone Trial).

OBJECTIVES: This substudy tested a prospective hypothesis that European Myocardial Infarct Amiodarone Trial (EMIAT) patients with depressed heart rate variability (HRV) benefit from amiodarone treatment. BACKGROUND: The EMIAT randomized 1,486 survivors of acute myocardial infarction (MI) aged < or =75 years with left ventricular ejection fraction (LVEF) < or =40% to amiodarone or placebo. Despite a reduction of arrhythmic mortality on amiodarone, all-cause mortality was not changed. METHODS: Heart rate variability was assessed from prerandomization 24-h Holter tapes in 1,216 patients (606 on amiodarone). Two definitions of depressed HRV were used: standard deviation of normal to normal intervals (SDNN) < or =50 ms and HRV index < or =20 units. The survival of patients with depressed HRV was compared in the placebo and amiodarone arms. A retrospective analysis investigated the prospective dichotomy limits. All tests were repeated in five subpopulations: patients with first MI, patients on beta-adrenergic blocking agents, patients with LVEF < or =30%, patients with Holter arrhythmia and patients with baseline heart rate > or =75 beats/min. RESULTS: Centralized Holter processing produced artificially high SDNN but accurate HRV index values. Heart rate variability index was < or =20 U in 363 (29.9%) patients (183 on amiodarone) with all-cause mortality 22.8% on placebo and 17.5% on amiodarone (23.2% reduction, p = 0.24) and cardiac arrhythmic mortality 12.8% on placebo and 4.4% on amiodarone (66% reduction, p = 0.0054). Among patients with prospectively defined depressed HRV, the largest reduction of all-cause mortality was in patients with first MI (placebo 17.9%, amiodarone 10.3%, 42.5% reduction, p = 0.079) and in patients with heart rate < or =75 beats/min (placebo 29.0%, amiodarone 19.3%, 33.7% reduction, p = 0.075). Among patients with first MI and depressed HRV, amiodarone treatment was an independent predictor of survival in a multivariate Cox analysis. The retrospective analysis found a larger reduction of mortality on amiodarone in 313 (25.7%) patients with HRV index < or =19 U: 23.9% on placebo and 17.1% on amiodarone (28.4% reduction, p = 0.15). This was more expressed in patients with first MI: 49.4% mortality reduction on amiodarone (p = 0.046), on beta-blockers: 69.0% reduction (p = 0.047) and with heart rate > or =75 beats/min: 37.9% reduction (p = 0.054). CONCLUSION: Measurement of HRV in a large set of centrally processed Holter recordings is feasible with robust methods of assessment. Patients with LVEF < or =40% and depressed HRV benefit from prophylactic antiarrhythmic treatment with amiodarone. However, this finding needs confirmation in an independent data set before clinical practice is changed.