Arrhythmogenic response to isoproterenol testing vs. exercise testing in arrhythmogenic right ventricular cardiomyopathy patients.

Aims: To compare the arrhythmic response to isoproterenol and exercise testing in newly diagnosed arrhythmogenic right ventricular cardiomyopathy (ARVC) patients. Methods and results: We studied isoproterenol [continuous infusion (45 µg/min) for 3 min] and exercise testing (workload increased by 30 W every 3 min) performed in consecutive newly diagnosed ARVC patients. Both tests were evaluated with regard to the incidence of (i) polymorphic premature ventricular contractions (PVCs) and couplet(s) or (ii) sustained or non-sustained ventricular tachycardia (VT) with left bundle branch block [excluding right ventricular outflow tract VT]; and compared to a control group referred for the evaluation of PVCs without structural heart disease. Thirty-seven ARVC patients (63.5% male, age 38 ± 16 years) were included. The maximal sinus rhythm heart rate achieved during isoproterenol testing was significantly lower compared to exercise testing (149 ± 17 bpm vs. 166 ± 19 bpm, P < 0.0001). However, the incidence of polymorphic ventricular arrhythmias was much higher during isoproterenol testing compared to exercise testing [33/37 (89.2%) vs. 16/37 (43.2%), P < 0.0001]. Interestingly, isoproterenol testing was arrhythmogenic in all 15 patients in whom baseline PVCs were reduced or suppressed during exercise testing. During both isoproterenol and exercise testing, control group presented a low incidence of ventricular arrhythmias compared to ARVC patients (8.1% vs. 89.2%, P < 0.0001 and 2.7% vs. 43.2%, P < 0.0001, respectively). Conclusions: The incidence of polymorphic ventricular arrhythmias is significantly higher during isoproterenol compared to exercise testing in newly diagnosed ARVC patients, suggesting its potential utility for the diagnosis.

Combination of principal component analysis and optical-flow motion compensation for improved cardiac MR thermometry.

The use of magnetic resonance (MR) thermometry for the monitoring of thermal ablation is rapidly expanding. However, this technique remains challenging for the monitoring of the treatment of cardiac arrhythmia by radiofrequency ablation due to the heart displacement with respiration and contraction. Recent studies have addressed this problem by compensating in-plane motion in real-time with optical-flow based tracking technique. However, these algorithms are sensitive to local variation of signal intensity on magnitude images associated with tissue heating. In this study, an optical-flow algorithm was combined with a principal component analysis method to reduce the impact of such effects. The proposed method was integrated to a fully automatic cardiac MR thermometry pipeline, compatible with a future clinical workflow. It was evaluated on nine healthy volunteers under free breathing conditions, on a phantom and in vivo on the left ventricle of a sheep. The results showed that local intensity changes in magnitude images had lower impact on motion estimation with the proposed method. Using this strategy, the temperature mapping accuracy was significantly improved.

Atrial fibrillation and rapid acute pacing regulate adipocyte/adipositas-related gene expression in the atria.

PURPOSE: Atrial fibrillation (AF) has been associated with increased volumes of epicardial fat and atrial adipocyte accumulation. Underlying mechanisms are not well understood. This study aims to identify rapid atrial pacing (RAP)/AF-dependent changes in atrial adipocyte/adipositas-related gene expression (AARE). METHODS: Right atrial (RA) and adjacent epicardial adipose tissue (EAT) samples were obtained from 26 patients; 13 with AF, 13 in sinus rhythm (SR). Left atrial (LA) samples were obtained from 9 pigs (5 RAP, 4 sham-operated controls). AARE was analyzed using microarrays and RT-qPCR. The impact of diabetes/obesity on gene expression was additionally determined in RA samples (RAP ex vivo and controls) from 3 vs. 6 months old ZDF rats. RESULTS: RAP in vivo of pigs resulted in substantial changes of AARE, with 66 genes being up- and 53 down-regulated on the mRNA level. Differential expression during adipocyte differentiation was confirmed using 3T3-L1 cells. In patients with AF (compared to SR), a comparable change in RA mRNA levels concerned a fraction of genes only (RETN, IGF1, HK2, PYGM, LOX, and NR4A3). RA and EAT were affected by AF to a different extent. In patients, concomitant disease contributes to AARE changes. CONCLUSIONS: RAP, and to lesser extent AF, provoke significant changes in atrial AARE. In chronic AF, activation of this gene panel is very likely mediated by AF itself, AF risk factors and concomitant diseases. This may facilitate the development of an AF substrate by increasing atrial ectopic fat and fat infiltration of the atrial myocardium.

Prevalence, characteristics, and prognosis role of type 1 ST elevation in the peripheral ECG leads in patients with Brugada syndrome.

BACKGROUND: Despite isolated reports of Brugada syndrome (BrS) in the inferior or lateral leads, the prevalence and prognostic value of ST elevation in the peripheral electrocardiographic (ECG) leads in patients with BrS remain poorly known. OBJECTIVE: To study the prevalence, characteristics, and prognostic value of type 1 ST elevation and ST depression in the peripheral ECG leads in a large cohort of patients with BrS. METHODS: ECGs from 323 patients with BrS (age 47 ± 13 years; 257 men) with spontaneous (n = 141) or drug-induced (n = 182) type 1 ECG were retrospectively reviewed. Two hundred twenty-five (70%) patients were asymptomatic, 72 (22%) patients presented with unexplained syncope, and 26 (8%) patients presented with sudden death (12 patients) or appropriated implantable cardioverter-defibrillator therapies (14 patients) at diagnosis or over a mean follow-up of 48 ± 34 months. RESULTS: Thirty (9%) patients presented with type 1 ST elevation in at least 1 peripheral lead (22 patients in the aVR leads, 2 in the inferior leads, 5 in both aVR and inferior leads, and 1 in the aVR and VL leads). Patients with type 1 ST elevation in the peripheral leads more often had mutations in the SCN5A gene, were more often inducible, had slower heart rate, and higher J-wave amplitude in the right precordial leads. Twenty-seven percent (8 of 30) of the patients with type 1 ST elevation in the peripheral leads experimented sudden death/appropriate implantable cardioverter-defibrillator therapy, whereas it occurred in only 6% (18 of 293) of other patients (P < .0001). In multivariate analysis, type 1 ECG in the peripheral leads was independently associated with malignant arrhythmic events (odds ratio 4.58; 95% confidence interval 1.7-12.32; P = .0025). CONCLUSIONS: Type 1 ST elevation in the peripheral ECG leads can be seen in 10% of the patients with BrS and is an independent predictor for a malignant arrhythmic event.

Towards optimized MR thermometry of the human heart at 3T.

Catheter ablation using radio frequency (RF) has been used increasingly for the treatment of cardiac arrhythmias and may be combined with proton resonance frequency shift (PRFS) -based MR thermometry to determine the therapy endpoint. We evaluated the suitability of two different MR thermometry sequences (TFE and TFE-EPI) and three blood suppression techniques. Experiments were performed without heating, using an optimized imaging protocol including navigator respiratory compensation, cardiac triggering, and image processing for the compensation of motion and susceptibility artefacts. Blood suppression performance and its effect on temperature stability were evaluated in the ventricular septum of eight healthy volunteers using multislice double inversion recovery (MDIR), motion sensitized driven equilibrium (MSDE), and inflow saturation by saturation slabs (IS). It was shown that blood suppression during MR thermometry improves the contrast-to-noise ratio (CNR), the robustness of the applied motion correction algorithm as well as the temperature stability. A gradient echo sequence accelerated by an EPI readout and parallel imaging (SENSE) and using inflow saturation blood suppression was shown to achieve the best results. Temperature stabilities of 2 °C or better in the ventricular septum with a spatial resolution of 3.5 × 3.5 × 8mm(3) and a temporal resolution corresponding to the heart rate of the volunteer, were observed. Our results indicate that blood suppression improves the temperature stability when performing cardiac MR thermometry. The proposed MR thermometry protocol, which optimizes temperature stability in the ventricular septum, represents a step towards PRFS-based MR thermometry of the heart at 3 T.

[Catheter ablation for atrial fibrillation]. / Ablation par radiofréquence de la fibrillation atriale.

The mainstay of treatment for atrial fibrillation (AF) remains pharmacological, however, catheter ablation, since an early attempt in 1994 has undergone many evolutions up to the present day whereby it has taken an increasing place in the management of this arrhythmia. In paroxysmal AF, the most recent studies report a success rate of more than 80% at 1 year of follow-up after a single procedure (free of symptoms without antiarrhythmic drugs). In persistent AF the technique continues to evolve with a success rates between 70% and 95% even if several long and complex procedures are often needed, which are not without risk, to achieve these results. With constant improvement in this field catheter ablation has become a valuable tool in the management strategy of AF.

[Identification of candidates for multisite pacing: results and presumed mechanisms of action after five years experience]. / Identification des patients candidats a la stimulation multisite. Résultats et mécanismes d'action supposés a l'issue d'une expérience monocentrique de 5 ans.

Biventricular resynchronisation is an additional therapeutic option in the management of refractory heart failure, with a functional and haemodynamic benefit as well as an improved morbidity and mortality. However, the rate of non-responsive patients has prompted a re-think about the presumed mechanisms of action for this procedure. This study aims to identify candidates more successfully. Based on five years experience in this centre, our work confirmed a medium and long term clinical benefit with multisite pacing. Nevertheless, there was evidence of a relative discordance between the functional benefit and the haemodynamic impact in terms of ejection fraction achieved with resynchronisation. While QRS narrowing appears to be a predictive factor for a successful procedure, the ECG alone is not sufficient to select 'unsynchronised' candidates. Statistical analysis reveals that before implantation the independent predictive factors to identify non-responsive patients include the presence of a complication of myocardial infarction and a low grade mitral leak. The limits of the ECG suggest a more mechanical than electrical approach to understanding the mechanisms of action for resynchronisation. Its effectiveness in cases of right bundle branch block confirm the hypothesis of left intra-ventricular conduction defects, not apparent on the surface ECG but accessible through new imaging techniques. Based on the hypothesis of delayed movement of the ventricular walls, the principle of resynchronisation aims to restore homogenous contraction. Echocardiography allows observation of electromechanical delay and opens new perspectives in the future for selecting patients for pacing. Ar

[Characterization of premature ventricular contraction initiating ventricular fibrillation]. / Caractéristiques morphologiques des extrasystoles ventriculaires initiatrices des fibrillations ventriculaires.

UNLABELLED: The aim of this study is to characterize the electrocardiographic features of premature ventricular contractions (PVC) from different anatomical region that trigger ventricular fibrillation (VF). METHODS AND RESULTS: 36 consecutives patients (20 males, 42+/-14 yrs) undergoing VF ablation from 7 centres were studied (22 with idiopathic VF, 4 associated with a long QT syndrome, 3 with Brugada syndrome, 4 with ischaemic cardiomyopathy and 3 associated with other substrate). Mapping of these PVC showed 2 different origins, which were then confirmed by ablation: right ventricular outflow tract (RVOT) (22%) and peripheral Purkinje network (81%). One patient had PVC from both origins (Brugada). RVOT PVC were frequent but had triggered only 5+/-5 episodes of VF for 26+/-33 months. Purkinje PVC were more likely to be present during electrical storm with 18+/-28 episodes of VF for 33+/-45 months. Right Purkinje PVC have a left bundle branch block with superior axis morphology whereas left Purkinje ones have a right bundle branch block. The axis of activation showed variation from inferior to superior depending on the area of origin from the Purkinje network and the exit site to the myocardium. However Purkinje PVC were characterized by short QRS duration (126+/-18 vs 145+/-13ms for RVOT PVC; p=0.05). In addition the coupling interval was significantly shorter compared to RVOT PVC (292+/-45 vs 358+/-37ms respectively; p=0.005). CONCLUSION: PVC initiating VF demonstrate specific electrocardiographic features that facilitate determination of their origin. Ablation of these typical PVC is feasible in order to reduce ICD shock.

Echocardiographic advances in atrial fibrillation and supraventricular arrhythmias.

Advances in echocardiography have paved the way for the development of intracardiac catheters with ultrasound transducers mounted on its tip. With this technology it has become possible for the interventional electrophysiologist to perform continuous echocardiographic examination during a procedure without the need for general anaesthesia or additional staff. Intracardiac echocardiography (ICE) allows the monitoring of catheter movement in real-time, assessment of catheter-tissue contact and potentially prevents and recognizes complications like thrombus formation and pericardial effusion. In addition recent technologies allow acquiring the full spectrum of Doppler-imaging permitting evaluation of haemodynamic data during the procedure. All these advances have made ICE an ideal tool for the interventional electrophysiologist, serving as a diagnostic and imaging tool during invasive electrophysiological procedures. This review will summarize currently available technology of ICE and its indications and applications in electrophysiological procedures.

[Mapping and ablation of malignant ventricular arrhythmias]. / Cartographie et ablation des arythmies ventriculaires malignes.

Endocavitary investigations showed that the ventricular extrasystoles originated in the common ventricular myocardium (pulmonary infundibulum) in only 9 cases whereas the majority arose from the Parkinje system either on the anterior wall of the right ventricle or in septal region of the left ventricle. The extrasystoles arising from the Parkinje system and pulmonary infundibulum differed in their duration and polymorphism (128 +/- 18 ms vs 145 +/- 13 ms, p = 0.05; 3.3 +/- 2.7 morphologies vs 1.1 +/- 0.4, p < 0.001, respectively). During the extrasystoles, the local Pukinje potential preceded the ventricular activation by variable intervals, some of which were very long, up to 150 ms. Seven applications of radiofrequency were delivered on average per patient on the most distal part of the Purkinje system leading to ablation of the specific activation. The clinical results were spectacular: 88% of patients had no further episodes of ventricular fibrillation as demonstrated by analysis of the defibrillator with an average follow-up period of more than 34 months.

Catheter ablation for atrial fibrillation.

Recent advancements in our understanding of atrial fibrillation have led to the development of catheter ablation techniques that feasibly could achieve a cure for AF.

[The place of ablation in the treatment of atrial fibrillation: where are we and where are we going?]. / Place de l'ablation dans le traitement de la fibrillation auriculaire: où en sommes-nous? où allons-nous?

Atrial fibrillation, the most common arrhythmia, is frequently disabling and drug resistant and is associated with significant complications, especially thromboembolic events. Non-pharmacological approaches including surgery and catheter-based ablation have been developed for the most symptomatic patients. These new treatment strategies have dramatically increased our knowledge of the pathophysiology of this arrhythmia but most importantly have demonstrated that atrial fibrillation is curable. Since 1994, 2 different concepts have been used, aiming to modify the substrate responsible for AF maintenance using linear lesions, or to ablate the triggers located from within the pulmonary veins (PV) in about 90% of cases. The vast majority of the laboratories in the world are now using approaches centred on isolation of the PV. These approaches are far from being perfect but good enough to be offered in routine practice to selected patients in experienced centres. The importance of PVs in the initiation of AF has been clearly demonstrated and they also have a possible role in the maintenance of AF. However, the existence of non venous foci or a prominent substrate for AF maintenance limits the success rate to about 70%. As a consequence, a combination of PV isolation and linear lesions is commonly used. This more complex procedure carries a significantly higher success rate however with an increased risk of tamponade. As a consequence, we need to identify which patients will require linear lesions in addition to PV isolation. At the present time, AF ablation is restricted to symptomatic patients who have failed at least 1-2 antiarrhythmic drugs but future technical improvements based on presently applied concepts are likely to widen the indications for ablation therapy of AF.

Mapping and ablation of ventricular fibrillation.

Sudden cardiac death frequently results from ventricular fibrillation (VF). While VF is frequently the eventual mode of death in patients with abnormal ventricular substrates, it has also been described in patients with structurally normally hearts. Until recently, the management of patients who have survived sudden cardiac death has focused on treating the consequences by implantation of a defibrillator. However, such therapy remains restricted in many countries, is associated with a prohibitive cost to the community, and may be a cause of significant morbidity in patients with frequent episodes or storms of arrhythmia. Evidence emerging from the study of fibrillation both in the atria and the ventricle suggests an important role for triggers arising from the Purkinje network or the right ventricular outflow tract in the initiation of VF. Initial experience in patients with idiopathic VF and even those with VF associated with abnormal repolarization syndromes (LQT or Brugada syndrome) or myocardial infarction suggests that long term suppression of recurrent VF may be feasible by the elimination of these triggers. With the development of new mapping and ablation technologies, and greater physician experience, catheter ablation of VF, with the ultimate aim of curing such patients at risks of sudden cardiac death, may not be an unrealistic goal in the future.

[Catheter ablation of paroxysmal atrial fibrillation]. / Ablation endocavitaire des fibrillations atriales paroxystiques.

UNLABELLED: Catheter ablation techniques for atrial fibrillation have undergone an extensive evolution, starting with linear lesions in the right, then the left atria before being superseded by ablation of triggers, mainly from the pulmonary veins. We investigate the feasibility and results of combined pulmonary vein and linear ablation utilizing a specific linear lesion connecting the lateral mitral annulus to the left inferior pulmonary vein (left isthmus). METHODS: 115 patients (101 M: 54 +/- 9 years) with paroxysmal atrial fibrillation (7 +/- 5 years) resistant to 4 +/- 1.6 anti-arrhythmic drugs were studied. After electrophysiologically guided disconnection of all four pulmonary veins, the left isthmus line was performed with an irrigated tip catheter. Complete linear block was demonstrated during coronary sinus pacing by local mapping looking for widely separated double potentials and confirmed by differential pacing. Mapping and ablation from within the coronary sinus was performed if an epicardial gap was detected after unsuccessful endocardial radiofrequency delivery. RESULTS: 100% of pulmonary veins were successfully disconnected and the left isthmus line was complete with bi-directional block in 88% after a mean of 22 +/- 12 min of endocardial radiofrequency delivery in 44 patients. In 58 patients, additional radiofrequency delivery was required from within the coronary sinus for 5 +/- 5 min. After a follow-up of 6.5 +/- 2.6 months and a mean of 1.4 +/- 0.6 procedures/patient, 79% were in stable sinus rhythm without antiarrhythmic drugs. CONCLUSION: the left isthmus line is feasible and safe and when performed in addition to pulmonary veins isolation can contribute to an increased success rate.

[Radiofrequency ablation of atrial fibrillation]. / Ablation par radiofréquence de la fibrillation auriculaire.

The possibility of curing patients suffering from paroxysmal atrial fibrillation using a radiofrequency ablation treatment is a major change in the management of this arrhythmia. Pulmonary vein disconnection is efficient and safe after a learning curve of the operator. This pulmonary vein isolation is the first and mandatory step allowing disappearance of atrial fibrillation in 70% of the patients. Modification in fibrillatory substrate using linear lesions increases the rate success to 75% in chronic atrial fibrillation and to 82% in paroxysmal atrial fibrillation. The radiofrequency ablation of atrial fibrillation should be considered as a surgical treatment without an open heart, isolating structures and cutting tissues are technical improvements (new radiofrequency catheters) will probably facilitate in the future. Some comparative studies with medical treatment are currently evaluating their efficacy, safety and respective cost and they may lead to a considerable increase in the number of patients who could benefit from these curative treatments.

Interventricular and intra-left ventricular electromechanical delays in right ventricular paced patients with heart failure: implications for upgrading to biventricular stimulation.

OBJECTIVE: To correlate, in patients with right ventricular pacing (RVP), the QRS width with electromechanical variables assessed by pulsed Doppler tissue imaging echocardiography. Secondly, to find reliable parameters for selecting RVP patients who would respond to biventricular pacing (BVP). METHODS: 26 randomly selected control patients with RVP (mean (SD) ejection fraction 74 (3)%) (group A) were matched on sex and age criteria with 16 RVP patients with drug resistant heart failure (mean (SD) ejection fraction 27 (5)%) (group B). All patients were pacemaker dependent and all underwent pulsed Doppler tissue imaging echocardiography. This technique provided the intra-left ventricular (LV) electromechanical delay and the interventricular electromechanical delay. The Gaussian curve properties of data from group A patients provided the normal range of ECG and echographic parameters. DESIGN: Prospective study. SETTING: University hospital (tertiary referral centre). RESULTS: Data from the control group showed that an interventricular electromechanical delay or an intra-LV electromechanical delay > 50 ms would identify patients with a significantly abnormal ventricular mechanical asynchrony (p < 0.05). In the same manner, a QRS width > 190 ms was considered significantly larger in group B patients (p < 0.05) than in controls. In Group B patients, there was no correlation between the QRS width and the interventricular electromechanical delay (r = -0.23, NS) or the intra-LV electromechanical delay (r = 0.19, NS). Seven group B patients (44%) were misclassified by ECG criteria for ventricular mechanical asynchrony identification: four patients (25%) had a QRS width similar to that of controls but with a significantly prolonged intra-LV electromechanical delay and interventricular electromechanical delay; and three patients (19%) had a QRS width significantly larger than that in controls but without significant ventricular mechanical asynchrony. CONCLUSIONS: The QRS width is not a reliable tool to identify RVP patients with ventricular mechanical asynchrony. In RVP patients, an interventricular electromechanical delay or intra-LV electromechanical delay > 50 ms reflects a significant ventricular mechanical asynchrony and should be required to select patients for upgrading to BVP.

High impedance leads and safety margin. Electrical considerations based on a simplified expression of the 'paradigm'.

For physicians who are not familiar with the electrical basis of cardiac stimulation, high impedance leads previously (10 years ago) considered as bad electrodes (high voltage) are now considered as the 'epitome' of lead technology (low energy drain): clearly impedance is not a good parameter for characterizing the qualities of a pacing lead. Using a simplified approach to the electrostimulation 'paradigm', it is easy to establish that modern high impedance leads are in fact high current density leads and high efficiency leads (better description). It is also possible to establish that routine programming of the safety margin at 100% above threshold parameters is associated with a decrease in the penetration of the electric field according to the reduction of the cathode surface area. For safety and energy saving, a small tip electrode could be combined with a low polarization surface treatment and a reduction in fibrosis development between electrode and myocardium.

[Role of radiofrequency ablation in atrial fibrillation]. / Place de l'ablation par radiofréquence dans la fibrillation auriculaire.

Atrial fibrillation is the most frequently encountered arrhythmia in the human species. Its danger is widely appreciated but it remains for certain patients and their practitioners an awkward or even exasperating problem. Only surgery and radiofrequency ablation allow certain patients to be cured. The surgical approach is of course warranted in the case of an otherwise necessary cardiac intervention. In the absence of a surgical indication, endovenous ablation, which is less aggressive, is preferred. The procedure consists of disconnecting the pulmonary veins which "house" 80 to 95% of the foci, together with the ablation of further non-venous foci, which are always difficult to treat. Side effects in experimental centres are rare and 70% of patients are cured, which allows cessation of antiarrhythmic and anticoagulant treatments. The procedure is currently offered to symptomatic patients having had at least one episode every ten days in spite of antiarrhythmics.

Comparison of permanent left ventricular and biventricular pacing in patients with heart failure and chronic atrial fibrillation: prospective haemodynamic study.

OBJECTIVE: To compare clinical and haemodynamic variables between left ventricular and biventricular pacing in patients with severe heart failure; and to analyse haemodynamic changes during daily life and maximum exercise during chronic left ventricular and biventricular pacing. DESIGN: Prospective single blinded randomised study with crossover. SETTING: University hospital (tertiary referral centre). PATIENTS AND METHODS: 13 patients (mean (SD) age, 62 (6) years) with chronic atrial fibrillation, severe heart failure (mean ejection fraction 24 (8)%), and QRS prolongation of > or = 140 ms had His bundle ablation and installation of a pacemaker providing left ventricular and biventricular pacing. The pacemaker was equipped with a peak endocardial acceleration (PEA) sensor. The PEA pattern was used as a haemodynamic marker during exercise as it is highly correlated with left ventricular dP/dt. After a baseline period of right ventricular pacing, all patients had two months of left ventricular pacing and two months of biventricular pacing in random order. At the end of each phase, an echocardiogram, a haemodynamic analysis at rest and on exercise during a six minute walk test, and a cardiopulmonary exercise test were performed. RESULTS: PEA values were higher with left ventricular pacing (0.58 (0.38) m/s) and biventricular pacing (0.62 (0.24) m/s) than at baseline (0.49 (0.18) m/s) (p < 0.05). The six minute walk test showed similar performance in both pacing modes, but patients had more symptoms with left ventricular pacing at the end of the test (p = 0.035). On cardiopulmonary exercise testing, there was a greater increase in mean percentage variation of PEA with biventricular pacing than with left ventricular pacing (125 (18)% v 97 (36)%, respectively; p = 0.048) and better performance figures (92 (34) W v 77 (23) W; p = 0.03). CONCLUSIONS: During symptom limited and daily life exercise tests, chronic biventricular pacing provides better haemodynamic performance than left ventricular pacing. In heart failure patients with wide QRS complexes, the interventricular dyssynchronisation induced by left ventricular pacing may impair myocardial function during exercise.