Electrocardiographic recording direction impacts ventricular fibrillation waveform measurements: A potential pitfall for VF-waveform guided defibrillation protocols.

AIM: In cardiac arrest, ventricular fibrillation (VF) waveform analysis has identified the amplitude spectrum area (AMSA) as a key predictor of defibrillation success and favorable neurologic survival. New resuscitation protocols are under investigation, where prompt defibrillation is restricted to cases with a high AMSA. Appreciating the variability of in-field pad placement, we aimed to assess the impact of recording direction on AMSA-values, and the inherent defibrillation advice. METHODS: Prospective VF-waveform study on 12-lead surface electrocardiograms (ECGs) obtained during defibrillation testing in ICD-recipients (2010-2017). AMSA-values (mVHz) of simultaneous VF-recordings were calculated and compared between all limb leads, with lead II as reference (proxy for in-field pad position). AMSA-differences between leads I and II were quantified using Bland-Altman analysis. Moreover, we investigated differences between these adjacent leads regarding classification into high (≥15.5), intermediate (6.5-15.5) or low (≤6.5) AMSA-values. RESULTS: In this cohort (n = 243), AMSA-values in lead II (10.2 ± 4.8) differed significantly from the other limb leads (I: 8.0 ± 3.4; III: 12.9 ± 5.6, both p < 0.001). The AMSA-value in lead I was, on average, 2.24 ± 4.3 lower than in lead II. Of the subjects with high AMSA-values in lead II, only 15% were classified as high if based on assessments of lead I. For intermediate and low AMSA-values, concordances were 66% and 72% respectively. CONCLUSIONS: ECG-recording direction markedly affects the result of VF-waveform analysis, with 20-30% lower AMSA-values in lead I than in lead II. Our data suggest that electrode positioning may significantly impact shock guidance by 'smart defibrillators', especially affecting the advice for prompt defibrillation.

Computerized Analysis of the Ventricular Fibrillation Waveform Allows Identification of Myocardial Infarction: A Proof-of-Concept Study for Smart Defibrillator Applications in Cardiac Arrest.

Background In cardiac arrest, computerized analysis of the ventricular fibrillation (VF) waveform provides prognostic information, while its diagnostic potential is subject of study. Animal studies suggest that VF morphology is affected by prior myocardial infarction (MI), and even more by acute MI. This experimental in-human study reports on the discriminative value of VF waveform analysis to identify a prior MI. Outcomes may provide support for in-field studies on acute MI. Methods and Results We conducted a prospective registry of implantable cardioverter defibrillator recipients with defibrillation testing (2010-2014). From 12-lead surface ECG VF recordings, we calculated 10 VF waveform characteristics. First, we studied detection of prior MI with lead II, using one key VF characteristic (amplitude spectrum area [AMSA]). Subsequently, we constructed diagnostic machine learning models: model A, lead II, all VF characteristics; model B, 12-lead, AMSA only; and model C, 12-lead, all VF characteristics. Prior MI was present in 58% (119/206) of patients. The approach using the AMSA of lead II demonstrated a C-statistic of 0.61 (95% CI, 0.54-0.68). Model A performance was not significantly better: 0.66 (95% CI, 0.59-0.73), P=0.09 versus AMSA lead II. Model B yielded a higher C-statistic: 0.75 (95% CI, 0.68-0.81), P<0.001 versus AMSA lead II. Model C did not improve this further: 0.74 (95% CI, 0.67-0.80), P=0.66 versus model B. Conclusions This proof-of-concept study provides the first in-human evidence that MI detection seems feasible using VF waveform analysis. Information from multiple ECG leads rather than from multiple VF characteristics may improve diagnostic accuracy. These results require additional experimental studies and may serve as pilot data for in-field smart defibrillator studies, to try and identify acute MI in the earliest stages of cardiac arrest.

Meta-Analysis Comparing Cardiac Arrest Outcomes Before and After Resuscitation Guideline Updates.

Updates of resuscitation guidelines have limited high-level supporting evidence. Moreover, the overall effect of such bundled practice changes depends not only on the impact of the individual interventions but also on their interplay and swift functioning of the entire chain of survival. Therefore, real-world data monitoring is essential. We performed a meta-analysis of comparative studies on outcomes before and after successive guideline updates. On January 16, 2019, we searched for comparative studies (PubMed, Web-of-Science, Embase, and the Cochrane Libraries) reporting outcomes before and after resuscitation guidelines 2005, 2010, and 2015. We followed PRISMA, Cochrane, and Moose-recommendations. Studies on outcomes during the 2005 versus 2000 guideline period (n = 23; 40,859 patients) reported significantly higher ROSC (odds ratio [OR] 1.21 [1.04 to 1.42], p = 0.014), survival to admission (OR 1.34 [1.09 to 1.65], p = 0.005), survival to discharge (OR 1.46 [1.25 to 1.70], p <0.001), and favorable neurologic outcome (OR 1.35 [1.01 to 1.81], p = 0.040). Studies on outcomes during the 2010 versus 2005 guideline period (n = 11; 1,048,112 patients) indicated no difference in ROSC (OR 1.25 [95% confidence interval 0.95 to 1.63], p = 0.11), whereas survival to discharge improved significantly (OR 1.30 [1.17 to 1.45], p <0.001). Only 2 studies reported on neurologic outcomes, both showing improved outcome after the 2010 guideline update. No data on the 2015 guidelines were available. This meta-analysis on real-world data of >1 million patients demonstrates improved outcomes after the 2005 and 2010 resuscitation guideline updates, and a lack of data on the 2015 guideline. In conclusion, although limited in terms of causality, this study suggests that the sum of all efforts to improve outcomes, including updated CPR guidelines, contributed to increased survival after cardiac arrest.

Ventricular fibrillation waveform characteristics of the surface ECG: Impact of the left ventricular diameter and mass.

BACKGROUND: Despite a promising association between VF waveform characteristics and prognosis after resuscitation, studies with VF-guided treatment have so far not improved outcomes. While driven by the idea that the VF waveform reflects arrest duration, increasing evidence suggests that pre-existent disease-related changes of the myocardium affect ECG-characteristics of VF as well. In this context, we studied the impact of the left ventricular (LV) diameter and mass. METHODS: Cohort of 193 ICD-patients with defibrillation testing at the Radboudumc (2010-2014). Surface ECG-recordings (leads I,II,aVF,V1,V3,V6) were analysed to study amplitude and frequency characteristics of the induced VF. Both for LV diameter and mass, patients were categorised in two groups, using echocardiographic data (ASE-guidelines). RESULTS: In all ECG-leads, dominant and median frequencies were significantly lower in patients with (n=40) than in patients without (n=151) an increased LV diameter. The mean amplitude and amplitude spectrum area (AMSA) did not differ. In contrast, we observed no differences in frequency characteristics in relation to the LV mass, whereas mean amplitude (I,aVF,V3) and AMSA (I,V3) were significantly higher in patients with (n=57) than in patients without (n=120) an increased LV mass. CONCLUSIONS: Frequency characteristics of VF were consistently lower in case of an increased LV diameter. Whereas LV mass does not affect the frequency of the VF waveform, amplitudes seem higher with increasing mass. These findings add to the current knowledge of factors that modulate VF characteristics of the surface ECG and provide insight into factors which may be accounted for in future studies on VF-guided resuscitative interventions.

Termination of resuscitation in the prehospital setting: A comparison of decisions in clinical practice vs. recommendations of a termination rule.

BACKGROUND: Of the proposed algorithms that provide guidance for in-field termination of resuscitation (TOR) decisions, the guidelines for cardiopulmonary resuscitation (CPR) refer to the basic and advanced life support (ALS)-TOR rules. To assess the potential consequences of implementation of the ALS-TOR rule, we performed a case-by-case evaluation of our in-field termination decisions and assessed the corresponding recommendations of the ALS-TOR rule. METHODS: Cohort of non-traumatic out-of-hospital cardiac arrest (OHCA)-patients who were resuscitated by the ALS-practising emergency medical service (EMS) in the Nijmegen area (2008-2011). The ALS-TOR rule recommends termination in case all following criteria are met: unwitnessed arrest, no bystander CPR, no shock delivery, no return of spontaneous circulation (ROSC). RESULTS: Of the 598 cases reviewed, resuscitative efforts were terminated in the field in 46% and 15% survived to discharge. The ALS-TOR rule would have recommended in-field termination in only 6% of patients, due to high percentages of witnessed arrests (73%) and bystander CPR (54%). In current practice, absence of ROSC was the most important determinant of termination [aOR 35.6 (95% CI 18.3-69.3)]. Weaker associations were found for: unwitnessed and non-public arrests, non-shockable initial rhythms and longer EMS-response times. CONCLUSION: While designed to optimise hospital transportations, application of the ALS-TOR rule would almost double our hospital transportation rate to over 90% of OHCA-cases due to the favourable arrest circumstances in our region. Prior to implementation of the ALS-TOR rule, local evaluation of the potential consequences for the efficiency of triage is to be recommended and initiatives to improve field-triage for ALS-based EMS-systems are eagerly awaited.

Risk Factors for Inadequate Defibrillation Safety Margins Vary With the Underlying Cardiac Disease: Implications for Selective Testing Strategies.

INTRODUCTION: In view of the shift from routine toward no or selective defibrillation testing, optimization of the current risk stratification for inadequate defibrillation safety margins (DSMs) could improve individualized testing decisions. Given the pathophysiological differences in myocardial substrate between ischemic and nonischemic heart disease (IHD/non-IHD) and the accompanying differences in clinical characteristics, we studied inadequate DSMs and their predictors in relation to the underlying etiology. METHODS AND RESULTS: Cohort of routine defibrillation tests (n = 785) after first implantable cardioverter defibrillator (ICD)-implantations at the Radboud UMC (2005-2014). A defibrillation threshold >25 J was regarded as an inadequate DSM. In total, 4.3% of patients had an inadequate DSM; in IHD 2.5% versus 7.3% in non-IHD (P = 0.002). We identified a group of non-IHD patients at high risk (13-42% inadequate DSM); the remainder of the cohort (>70%) had a risk of only 2% (C-statistic entire cohort 0.74; C-statistic non-IHD 0.82). This was based upon two identified interaction terms: (1) non-IHD and age (aOR 0.94 [95% CI 0.91-0.97]); (2) non-IHD and the indexed left ventricular (LV) internal diastolic diameter (aOR 3.50 [95% CI 2.10-5.82]). CONCLUSION: The present study on risk stratification for an inadequate DSM not only confirms the importance of making a distinction between IHD and non-IHD, but also shows that risk factors in an entire cohort (LV dilatation, age) may only apply to a subgroup (non-IHD). Appreciation of this concept could favorably affect current risk stratification. If confirmed, our approach may be used to optimize individualized testing decisions in an upcoming era of non-routine testing.

Manual Cardiopulmonary Resuscitation Versus CPR Including a Mechanical Chest Compression Device in Out-of-Hospital Cardiac Arrest: A Comprehensive Meta-analysis From Randomized and Observational Studies.

STUDY OBJECTIVE: Mechanical chest compression devices have been developed to facilitate continuous delivery of high-quality cardiopulmonary resuscitation (CPR). Despite promising hemodynamic data, evidence on clinical outcomes remains inconclusive. With the completion of 3 randomized controlled trials, we conduct a meta-analysis on the effect of in-field mechanical versus manual CPR on clinical outcomes after out-of-hospital cardiac arrest. METHODS: With a systematic search (PubMed, Web of Science, EMBASE, and the Cochrane Libraries), we identified all eligible studies (randomized controlled trials and nonrandomized studies) that compared a CPR strategy including an automated mechanical chest compression device with a strategy of manual CPR only. Outcome variables were survival to hospital admission, survival to discharge, and favorable neurologic outcome. RESULTS: Twenty studies (n=21,363) were analyzed: 5 randomized controlled trials and 15 nonrandomized studies, pooled separately. For survival to admission, the pooled estimate of the randomized controlled trials did not indicate a difference (odds ratio 0.94; 95% confidence interval 0.84 to 1.05; P=.24) between mechanical and manual CPR. In contrast, meta-analysis of nonrandomized studies demonstrated a benefit in favor of mechanical CPR (odds ratio 1.42; 95% confidence interval 1.21 to 1.67; P<.001). No interaction was found between the endorsed CPR guidelines (2000 versus 2005) and the CPR strategy (P=.27). Survival to discharge and neurologic outcome did not differ between strategies. CONCLUSION: Although there are lower-quality, observational data that suggest that mechanical CPR used at the rescuer's discretion could improve survival to hospital admission, the cumulative high-quality randomized evidence does not support a routine strategy of mechanical CPR to improve survival or neurologic outcome. These findings are irrespective of the endorsed CPR guidelines during the study periods.

Ventricular fibrillation waveform characteristics differ according to the presence of a previous myocardial infarction: A surface ECG study in ICD-patients.

BACKGROUND: Characteristics of the ventricular fibrillation (VF) waveform reflect arrest duration and have been incorporated in studies on algorithms to guide resuscitative interventions. Findings in animals indicate that VF characteristics are also affected by the presence of a previous myocardial infarction (MI). As studies in humans are scarce, we assessed the impact of a previous MI on VF characteristics in ICD-patients. METHODS: Prospective cohort of ICD-patients (n=190) with defibrillation testing at the Radboudumc (2010-2013). VF characteristics of the 12-lead surface ECG were compared between three groups: patients without a history of MI (n=88), with a previous anterior (n=47) and a previous inferior MI (n=55). RESULTS: As compared to each of the other groups, the mean amplitude and amplitude spectrum area were lower, for an anterior MI in lead V3 and for an inferior MI in leads II and aVF. Across the three groups, the bandwidth was broader in the leads corresponding with the infarct localisation. In contrast, the dominant and median frequencies only differed between previous anterior MI and no history of MI, being lower in the former. CONCLUSIONS: The VF waveform is affected by the presence of a previous MI. Amplitude-related measures were lower and VF was less organised in the ECG-lead(s) adjacent to the area of infarction. Although VF characteristics of the surface ECG have so far primarily been considered a proxy for arrest duration and metabolic state, our findings question this paradigm and may provide additional insights into the future potential of VF-guided resuscitative interventions.

Characteristics of ventricular fibrillation in relation to cardiac aetiology and shock success: A waveform analysis study in ICD-patients.

BACKGROUND: Ventricular fibrillation (VF) waveform characteristics are associated with cardiac arrest duration and defibrillation success. Recent animal studies found that VF characteristics and shock success also depend on the presence of myocardial infarction (MI). In patients, VF induction after implantable cardioverter defibrillator (ICD) implantation offers a unique setting to study early VF characteristics: we studied the relation with cardiac disease--either presence or absence of a previous MI--and with shock success. METHODS: Retrospective cohort study of ICD-patients who underwent defibrillation testing, 117 (63%) with and 69 (37%) without a previous MI. Intracardiac recordings of induced VF were analysed using Fourier analysis. RESULTS: In previous MI-patients, the fundamental frequency and organisation index of the VF signal were significantly lower as compared with patients without a previous MI: 4.9 Hz ± 0.6 vs. 5.2 Hz ± 0.6 (p = 0.005) and 56% ± 10 vs. 60% ± 9 (p = 0.001), respectively. The median frequency was not different (p = 0.25). We found no association between VF characteristics and ICD shock success. CONCLUSIONS: In analogy with observations in animals, we found that a history of a previous MI was associated with slower and less organised VF. In our cohort of ICD-patients, early VF waveform characteristics were not associated with shock outcomes. Further study is warranted to determine to what extent VF characteristics are influenced by the underlying aetiology on the one hand, and time delay on the other. These findings could improve insight into the potential value of VF analysis to guide shock delivery.

Legal responsibilities of physicians when making participation decisions in athletes with cardiac disorders: Do guidelines provide a solid legal footing?

Safe sports participation involves protecting athletes from injury and life-threatening situations. Preparticipation cardiovascular screening (PPS) in athletes is intended to prevent exercise-related sudden cardiac death by medical management of athletes at risk, which may include disqualification from sports participation. The screening physician relies on current guidelines and expert recommendations for management and decision-making. There is concern about false-positive screening results and wrongly grounding an athlete. Similarly, there is a concern about false-negative screening results and athletes participating with potentially lethal disorders. Who is legally responsible if an athlete suddenly dies after a proper PPS resulting in low risk? Several consensus documents based on expert opinion describe only a few lines on legal responsibilities in eligibility screening and disqualification decision-making in athletes. This article discusses legal responsibilities and concerns in eligibility decision-making for physicians.

Aspirin versus vitamin K antagonist treatment guided by transoesophageal echocardiography in patients with atrial fibrillation: a pilot study.

OBJECTIVE: Current stroke risk schemes need improvement of predictive value in patients with atrial fibrillation. Transoesophageal echocardiography (TEE) may facilitate stroke risk assessment in such patients and guide antithrombotic treatment. METHODS: We randomised 238 patients with non-valvular atrial fibrillation and a moderate stroke risk to aspirin or adjusted vitamin K antagonist therapy after TEE had ruled out thrombogenic features in the atria and aorta. The primary outcome was a composite of stroke, major bleeding, peripheral embolism and all-cause mortality. RESULTS: Mean CHA2DS2-VASc score was 2.1±1.1. The incidences of the composite primary outcome at a mean follow-up of 1.6 years were 3.2% (2.02% per year) in the aspirin group compared to 6.1% (3.84% per year) in the vitamin K antagonists group with an absolute advantage of 2.9 percentage points. Aspirin was non-inferior to vitamin K antagonists (p<0.0001) because the upper limit of the 90% CI did not exceed the 7% absolute difference in event rate between the two treatment arms. CONCLUSIONS: This hypothesis-generating pilot trial has found that TEE may be used for refinement of stroke risk in paroxysmal atrial fibrillation patients. A larger trial is needed to confirm these data. (ClinicalTrials.gov number NTC00224757).

Fibrosis and electrophysiological characteristics of the atrial appendage in patients with atrial fibrillation and structural heart disease.

PURPOSE: This study was conducted to investigate the degree of fibrosis in atrial appendages of patients with and without atrial fibrillation (AF) undergoing cardiac surgery. In addition, we hypothesized that areas of atrial fibrosis can be identified by electrogram fractionation and low voltage for potential ablation therapy. METHODS: Interstitial fibrosis from right (RAA) and/or left atrial appendages (LAA) was studied in patients with sinus rhythm (SR, n = 8), paroxysmal (n = 21), and persistent AF (n = 20) undergoing coronary artery bypass and/or aortic or mitral valve surgery. Atrial fibrosis quantification was performed with Masson trichrome staining. Intraoperative bipolar epicardial electrophysiological measurements were performed to correlate fibrosis to electrogram fractionation, voltage, and AF cycle length. RESULTS: The average degree of fibrosis was 11.2 ± 7.2 % in the LAA and 22.8 ± 7.6 % in the RAA (p < 0.001). Fibrosis was not significantly higher in paroxysmal AF patients compared to SR subjects (18.2 ± 8.7 versus 20.7 ± 5.3 %). Persistent AF patients had a higher degree of LAA and RAA fibrosis compared to paroxysmal AF patients (LAA 14.6 ± 8.7 versus 8.6 ± 4.7 %, p = 0.02, and RAA 28.2 ± 7.9 versus 18.2 ± 8.7 %, respectively, p = 0.04). The left atrial end diastolic volume index was higher in persistent AF patients compared to SR controls (38.3 ± 16.4 and 28 ± 11 ml/m(2), respectively, p = 0.04). No correlation between atrial fibrosis and electrogram fractionation or voltage was found. CONCLUSION: Patients with structural heart disease undergoing cardiac surgery have more fibrosis in the RAA than in the LAA. Furthermore, RAA fibrosis is increased in persistent AF but not paroxysmal AF patients compared to control subjects. Electrogram fractionation and low voltage did not provide accurate identification of the fibrotic substrate.

High incidence of implantable cardioverter defibrillator malfunctions during radiation therapy: neutrons as a probable cause of soft errors.

AIMS: To investigate the behaviour of the implantable cardioverter defibrillator (ICD) function during actual radiotherapy sessions. METHODS AND RESULTS: Fifteen patients with an ICD underwent 17 radiation treatments for cancer [cumulative dose to the tumour was between 16 Gray (Gy) and 70 Gy; photon beams with maximum energies between 6 megaelectronvolt (MeV) and 18 MeV were employed]. During every session, the ICD was programmed to a monitoring mode to prevent inappropriate therapy delivery. Afterwards, the ICDs were interrogated to ensure proper function. Calculated radiation dose at the ICD site was <1 Gy in all patients. In 5 out of 17 radiation treatments (29%) the ICDs showed 6 malfunctions (35%). We noticed four disturbances in the memory data or device resets during radiation treatment and one case of inappropriate ventricular fibrillation detection due to external noise. In one case a late device data error was observed. All malfunctions occurred at 10 and 18 MeV beam energies. CONCLUSION: Despite the fact that all recommended precautions were taken to minimize the damage to the ICDs during radiotherapy and the calculated dose to the ICDs was <1 Gy, in 29% of the treatments a malfunction occurred. We observed a possible correlation between the beam energy and the malfunctions. This correlation may be due to an interaction between neutrons produced in the head of the linear accelerator at beam energies ≥10 MeV, and boron-10 which is present in the integrated circuit.

[Idiopathic ventricular tachycardia, an arrhythmia with good prognosis]. / Idiopathische ventrikeltachycardie, een ritmestoornis met gunstige prognose.

Three patients, one experiencing palpitations and two complaining of chest pain in stressful situations, appeared to have monomorphic wide complex tachycardia. After excluding channelopathy, structural abnormalities and ischaemia of the heart, this arrhythmia was classified as idiopathic. Symptoms disappeared in one patient after using metoprolol, a ß-adrenoceptor blocker. The other two patients were treated with radiofrequency ablation of the focus from which the tachycardias arose. Idiopathic ventricular tachycardia mostly arises from the right ventricular outflow tract. The diagnosis is made upon history taking, including family history, echocardiography, 12-lead ECG, exercise testing and 24-hour Holter monitoring. The prognosis is excellent and sudden cardiac death is rarely seen.

Electropathological substrate of longstanding persistent atrial fibrillation in patients with structural heart disease: epicardial breakthrough.

BACKGROUND: During persistent atrial fibrillation (AF), waves with a focal spread of activation are frequently observed. The origin of these waves and their relevance for the persistence of AF are unknown. METHODS AND RESULTS: In 24 patients with longstanding persistent AF and structural heart disease, high-density mapping of the right and left atria was performed during cardiac surgery. In a reference group of 25 patients, AF was induced by rapid pacing. For data analysis, a mapping algorithm was developed that separated the fibrillatory process into its individual wavelets and identified waves with a focal origin. During persistent AF, the incidence of focal fibrillation waves in the right atrium was almost 4-fold higher than during acute AF (median, 0.46 versus 0.12 per cycle per 1 cm² (25th to 75th percentile, 0.40 to 0.77 and 0.01 to 0.27; P<0.0001). They were widely distributed over both atria and were recorded at 46 ± 18 of all electrodes. A large majority (90.5) occurred as single events. Repetitive focal activity (>3) happened in only 0.8. The coupling interval was not more than 11 ms shorter than the average AF cycle length (P=0.04), and they were not preceded by a long interval. Unipolar electrograms at the site of origin showed small but clear R waves. These data favor epicardial breakthrough rather than a cellular focal mechanism as the underlying mechanism. Often, conduction from a site of epicardial breakthrough was blocked in 1 or more directions. This generated separate multiple wave fronts propagating in different directions over the epicardium. CONCLUSIONS: Focal fibrillation waves are due to epicardial breakthrough of waves propagating in deeper layers of the atrial wall. In patients with longstanding AF, the frequency of epicardial breakthroughs was 4 times higher than during acute AF. Because they provide a constant source of independent fibrillation waves originating over the entire epicardial surface, they offer an adequate explanation for the high persistence of AF in patients with structural heart disease.

Electropathological substrate of long-standing persistent atrial fibrillation in patients with structural heart disease: longitudinal dissociation.

BACKGROUND: The electropathological substrate of persistent atrial fibrillation (AF) in humans is largely unknown. The aim of this study was to compare the spatiotemporal characteristics of the fibrillatory process in patients with normal sinus rhythm and long-standing persistent AF. METHODS AND RESULTS: During cardiac surgery, epicardial mapping (244 electrodes) of the right atrium (RA), the left lateral wall (LA), and the posterior left atrium (PV) was performed in 24 patients with long-standing persistent AF. Twenty-five patients with normal sinus rhythm, in whom AF was induced by rapid pacing, served as a reference group. A mapping algorithm was developed that separated the complex fibrillation process into its individual elements (wave mapping). Parameters used to characterize the substrate of AF were (1) the total length of interwave conduction block, (2) the number of fibrillation waves, and (3) the ratio of block to collision of fibrillation waves (dissociation index). In 4403 maps of persistent AF, no evidence for the presence of stable foci or rotors was found. Instead, many narrow wavelets propagated simultaneously through the atrial wall. The lateral boundaries of these waves were formed by lines of interwave conduction block, predominantly oriented parallel to the atrial musculature. Lines of block were not fixed but continuously changed on a beat-to-beat basis. In patients with persistent AF, the total length of block in the RA was more than 6-fold higher than during acute AF (median, 21.1 versus 3.4 mm/cm(2); P<0.0001). The highest degree of interwave conduction block was found in the PV area (33.0 mm/cm(2)). The number of fibrillation waves during persistent AF was 4.5/cm(2) compared with 2.3 during acute AF, and the dissociation index was 7.3 versus 1.5 (P<0.0001). The interindividual variation of these parameters among patients was high. CONCLUSIONS: Electric dissociation of neighboring atrial muscle bundles is a key element in the development of the substrate of human AF. The degree of the pathological changes can be measured on an individual basis by electrophysiological parameters in the spatial domain.

An unusual cause of atrial tachycardia in a young patient with lymphoma.

An 8-year-old girl who was recently diagnosed as having anaplastic large-cell lymphoma presented with atrial tachycardia and dilated cardiomyopathy, which is a contraindication for further treatment with cardio-toxic chemotherapy. After starting digoxin therapy, the dilated cardiomyopathy resolved. Repeated episodes of atrial tachycardia in this case were not caused by any common disorder but were due to mechanical stimulation by a central venous catheter. Central venous catheters are known to cause mainly ventricular arrhythmias. However, atrial tachycardia is a rare manifestation of arrhythmia due to mechanical stimulation of the heart by a central venous catheter, with potentially important cardiovascular consequences.