G. Hindricks

Regional myocardial sympathetic dysinnervation in arrhythmogenic right ventricular cardiomyopathy. An analysis using 123I-meta-iodobenzylguanidine scintigraphy.

BackgroundIn patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), the frequent provocation of ventricular tachycardia during exercise, the sensitivity toward catecholamines, and the response toward antiarrhythmic drug regimen with antiadrenergic properties suggest an involvement of the sympathetic nervous system in arrhythmogenesis. Methods and ResultsTo analyze the presence, extent, and location of impaired myocardial sympathetic innervation in ARVC, 123I–meta-iodobenzylguanidine (123I-MIBG) scintigraphy was performed in 48 patients with ARVC. For comparison, 9 patients with idiopathic ventricular tachycardia and a control group of 7 patients without heart disease were investigated. In patients with ARVC, the clinical sustained (n=25; 52%) or nonsustained (n=23; 48%) ventricular tachycardia originated in the right ventricular outflow tract in 38 patients (79%), whereas in the remaining 10 patients (21%), the site of origin was the apical (n=5) or inferior (n=5) right ventricle. In 33 patients (69%), nonsustained or sustained ventricular tachycardia was provocable by exercise (n=28 of 48; 58%) and/or by isoproterenol infusion (n= 16 of 37; 43%), whereas programmed ventricular stimulation induced sustained or nonsustained ventricular tachycardia in 16 patients each (33% each). With I MIBG scintigraphy, the right ventricle was not visible in any patient. No areas of intense 11I-MIBG uptake (“hot spots”) were observed. All patients of the control group and 7 of 9 patients (78%) with idiopathic ventricular tachycardia showed a uniform tracer uptake in the left ventricle. In contrast, only 8 of 48 ARVC patients (17%) showed a homogeneous distribution of 123I-MIBG uptake, whereas 40 patients (83%) demonstrated regional reductions or defects of tracer uptake. In 3 of 48 patients (6%), the defect area was < 15%; in 21 patients (44%), it was 15% to 30%; and in 16 patients (33%), it was >30% of the polar map area of the left ventricle (mean, 23±15%; range, 0% to 57%). In 38 of 40 patients (95%) with an abnormal 123I-MIBG scan, reduced tracer uptake was located in the basal posteroseptal left ventricle, involving the adjacent lateral wall in 10, the anterior wall in 2, and the apex in 12 patients. Only 2 patients demonstrated isolated defects of the anterior or lateral wall; one involved the apex. Perfusion abnormalities in the areas of 123I-MIBG defects were excluded by stress/redistribution 201Tl single-photon emission computed tomography scintigraphy and by normal coronary angiograms in all patients. Abnormalities in 123I-MIBG scintigraphy in patients with ARVC correlated with the site of origin of ventricular tachycardia, demonstrating a regionally reduced tracer uptake in 36 of 38 patients (95%) with right ventricular outflow tract tachycardia compared with only 4 of 10 patients (40%) with other right ventricular origins of tachycardia. There was no correlation between the results of 123I-MIBG scintigraphy and the extent of right ventricular contraction abnormalities, right ventricular ejection fraction, biopsy results, coronary anatomy, or left ventricular involvement in ARVC. ConclusionsIn patients with ARVC, regional abnormalities of sympathetic innervation are frequent and can be demonstrated by 123I-MIBG scintigraphy. Sympathetic denervation appears to be the underlying mechanism of reduced 123I-MIBG uptake and may be related to frequent provocation of ventricular arrhythmias by exercise or catecholamine exposure in ARVC. Therefore, in patients with ARVC, the noninvasive detection of localized sympathetic denervation by 123I-MIBG imaging may have implications for the early diagnosis and for the choice of antiarrhythmic drugs in the treatment of arrhythmias.

Adverse effects of Wolff-Parkinson-White syndrome with right septal or posteroseptal accessory pathways on cardiac function

AIMS Wolff-Parkinson-White syndrome with right septal or posteroseptal accessory pathways causes eccentric septal mechanical activation and may provoke left ventricular (LV) dyssynchrony and dysfunction. The aim of the study was to evaluate the effect of radiofrequency catheter ablation (RFA) of the accessory pathways on LV function. METHODS AND RESULTS Retrospectively, transthoracic echocardiography and electrocardiogram recordings were analysed in 34 patients (age: 14.2 +/- 2.5 years) with right septal or posteroseptal accessory pathways prior and after (median: 1 day) successful RFA. Results prior to RFA, LV ejection fraction was decreased (<55%) in 19/34 patients (56%). After RFA, QRS duration was normalized (129 +/- 23 vs. 90 +/- 11, P < 0.0001), LV function improved (ejection fraction: 50 +/- 10 vs. 56 +/- 4%, P = 0.0005) and septal-to-posterior wall motion delay as a global measure for LV dyssynchrony decreased (110 +/- 94 vs. 66 +/- 53, P = 0.012). Longitudinal two-dimensional strain evaluated in five patients demonstrated a decrease of left intraventricular mechanical delay from 292 +/- 125 to 118 +/- 37 ms after RFA. CONCLUSION Wolff-Parkinson-White syndrome with right septal or posteroseptal accessory pathways may cause LV dyssynchrony and jeopardize global LV function. Radiofrequency catheter ablation resulted in normalized QRS duration, mechanical resynchronization, and improved LV function. Even in the absence of arrhythmias, RFA of right septal or posteroseptal pathways may be considered in patients with significantly decreased LV function.

EuroEco (European Health Economic Trial on Home Monitoring in ICD Patients): a provider perspective in five European countries on costs and net financial impact of follow-up with or without remote monitoring.

Aim Remote follow-up (FU) of implantable cardiac defibrillators (ICDs) allows for fewer in-office visits in combination with earlier detection of relevant findings. Its implementation requires investment and reorganization of care. Providers (physicians or hospitals) are unsure about the financial impact. The primary end-point of this randomized prospective multicentre health economic trial was the total FU-related cost for providers, comparing Home Monitoring facilitated FU (HM ON) to regular in-office FU (HM OFF) during the first 2 years after ICD implantation. Also the net financial impact on providers (taking national reimbursement into account) and costs from a healthcare payer perspective were evaluated. Methods and results A total of 312 patients with VVI- or DDD-ICD implants from 17 centres in six EU countries were randomised to HM ON or OFF, of which 303 were eligible for data analysis. For all contacts (in-office, calendar- or alert-triggered web-based review, discussions, calls) time-expenditure was tracked. Country-specific cost parameters were used to convert resource use into monetary values. Remote FU equipment itself was not included in the cost calculations. Given only two patients from Finland (one in each group) a monetary valuation analysis was not performed for Finland. Average age was 62.4 ± 13.1 years, 81% were male, 39% received a DDD system, and 51% had a prophylactic ICD. Resource use with HM ON was clearly different: less FU visits (3.79 ± 1.67 vs. 5.53 ± 2.32; P < 0.001) despite a small increase of unscheduled visits (0.95 ± 1.50 vs. 0.62 ± 1.25; P < 0.005), more non-office-based contacts (1.95 ± 3.29 vs. 1.01 ± 2.64; P < 0.001), more Internet sessions (11.02 ± 15.28 vs. 0.06 ± 0.31; P < 0.001) and more in-clinic discussions (1.84 ± 4.20 vs. 1.28 ± 2.92; P < 0.03), but with numerically fewer hospitalizations (0.67 ± 1.18 vs. 0.85 ± 1.43, P = 0.23) and shorter length-of-stay (6.31 ± 15.5 vs. 8.26 ± 18.6; P = 0.27), although not significant. For the whole study population, the total FU cost for providers was not different for HM ON vs. OFF [mean (95% CI): €204 (169–238) vs. €213 (182–243); range for difference (€−36 to 54), NS]. From a payer perspective, FU-related costs were similar while the total cost per patient (including other physician visits, examinations, and hospitalizations) was numerically (but not significantly) lower. There was no difference in the net financial impact on providers [profit of €408 (327–489) vs. €400 (345–455); range for difference (€−104 to 88), NS], but there was heterogeneity among countries, with less profit for providers in the absence of specific remote FU reimbursement (Belgium, Spain, and the Netherlands) and maintained or increased profit in cases where such reimbursement exists (Germany and UK). Quality of life (SF-36) was not different. Conclusion For all the patients as a whole, FU-related costs for providers are not different for remote FU vs. purely in-office FU, despite reorganized care. However, disparity in the impact on provider budget among different countries illustrates the need for proper reimbursement to ensure effective remote FU implementation.

Incidental and ablation-induced findings during upper gastrointestinal endoscopy in patients after ablation of atrial fibrillation: A retrospective study of 425 patients

BACKGROUND Although rare, atrioesophageal fistula is a serious and often lethal complication of radiofrequency catheter ablation in patients with atrial fibrillation (AF). Consequently, esophagogastroduodenoscopy after AF catheter ablation has been suggested to detect thermal esophageal lesions. OBJECTIVE To report the incidence of thermal lesions and other incidental gastrointestinal (GI) abnormalities in patients with AF after radiofrequency catheter ablation. METHODS Four hundred twenty-five (mean age 59 ± 10 years; 64% men) consecutive patients with symptomatic AF who underwent left atrial radiofrequency catheter ablation were scheduled for upper GI endoscopy 1-3 days after the procedure. Patients were asymptomatic for GI diseases, that is, exhibiting no dysphagia, heart burn, or abdominal pain. RESULTS Pathological GI findings were observed in 328 (77%) patients and included gastral erosions (22%), esophageal erythema (21%), gastroparesis (17%), hiatal hernia (16%), reflux esophagitis (12%), thermal esophageal lesion (11%), and suspected Barretts esophagus (5%). Biopsies were performed in 70 (17%) patients, showing gastritis (84%), Helicobacter pylori colonization (17%) and mucosa-associated lymphoid tissue (17%), esophagitis (9%), and Barretts esophagus (4%). Further diagnostic workup or treatment was initiated in 105 (25%) patients. CONCLUSIONS Upper GI pathologies are observed frequently in asymptomatic patients. Half of all patients have a requirement for treatment. Among the findings, thermal esophageal lesions and gastroparesis can be attributed to AF catheter ablation. The high incidence of gastroparesis is a novel finding that deserves further investigation.

Atypical Left Atrial Flutter after Intraoperative Radiofrequency Ablation of Chronic Atrial Fibrillation: Successful Ablation Using Three-Dimensional Electroanatomic Mapping

Left Atrial Flutter Ablation. Curative treatment of chronic atrial fibrillation (AF) remains a challenging task for electrophysiologists. Eliminating the initiating triggers by focal radiofrequency ablation in a subset of patients with paroxysmal AF and modifying the maintaining substrate by performing linear lesions within the left atrium in patients with prolonged episodes of AF are among the alternative approaches for management of these patients. Recently, a new intraoperative treatment procedure aimed at eliminating left atrial anatomic “anchor” reentrant circuits by induction of contiguous lesions using radiofrequency energy under direct vision was introduced. However, atypical left atrial flutter may occur during follow‐up after intraoperative ablation of AF. These arrhythmias most likely are due to discontinuities in linear lesions; therefore, they can be successfully mapped and ablated in a subsequent percutaneous catheter ablation procedure. We report and discuss the case of a patient who underwent successful intraoperative ablation of chronic AF, but who developed atypical left atrial flutter postoperatively. Three‐dimensional nonfluoroscopic electroanatomic mapping revealed a gap in the linear lesion line connecting the left upper and right upper pulmonary vein orifices. Ablation at the exit site of the breakthrough was successful.

Current controversies in determining the main mechanisms of atrial fibrillation.

Despite considerable basic research into the mechanisms of atrial fibrillation (AF), not much progress has been made in the prognosis of patients with AF. With the exception of anticoagulant therapy, current treatments for AF still do not improve major cardiovascular outcomes. This may be due partly to the diverse aetiology of AF with increasingly more factors found to contribute to the arrhythmia. In addition, a strong increase has been seen in the technological complexity of the methods used to quantify the main pathophysiological alterations underlying the initiation and progression of AF. Because of the lack of standardization of the technological approaches currently used, the perception of basic mechanisms of AF varies widely in the scientific community. Areas of debate include the role of Ca2+‐handling alterations associated with AF, the contribution and noninvasive assessment of the degree of atrial fibrosis, and the best techniques to identify electrophysiological drivers of AF. In this review, we will summarize the state of the art of these controversial topics and describe the diverse approaches to investigating and the scientific opinions on leading AF mechanisms. Finally, we will highlight the need for transparency in scientific reporting and standardization of terminology, assumptions, algorithms and experimental conditions used for the development of better AF therapies.

Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation: results on health-related quality of life and symptom burden. The MANTRA-PAF trial

AIMS The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial assessed the long-term efficacy of an initial strategy of radiofrequency ablation (RFA) vs. antiarrhythmic drug therapy (AAD) as first-line treatment for patients with PAF. In this substudy, we evaluated the effect of these treatment modalities on the Health-Related Quality of Life (HRQoL) and symptom burden of patients at 12 and 24 months. METHODS AND RESULTS During the study period, 294 patients were enrolled in the MANTRA-PAF trial and randomized to receive AAD (N = 148) or RFA (N = 146). Two generic questionnaires were used to assess the HRQoL [Short Form-36 (SF-36) and EuroQol-five dimensions (EQ-5D)], and the Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA) was used to evaluate the symptoms appearing during the trial. All comparisons were made on an intention-to-treat basis. Both randomization groups showed significant improvements in assessments with both SF-36 and EQ-5D, at 24 months. Patients randomized to RFA showed significantly greater improvement in four physically related scales of the SF-36. The three most frequently reported symptoms were breathlessness during activity, pronounced tiredness, and worry/anxiety. In both groups, there was a significant reduction in ASTA symptom index and in the severity of seven of the eight symptoms over time. CONCLUSION Both AAD and RFA as first-line treatment resulted in substantial improvement of HRQoL and symptom burden in patients with PAF. Patients randomized to RFA showed greater improvement in physical scales (SF-36) and the EQ-visual analogue scale. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT00133211.

Remodeling of cardiac passive electrical properties and susceptibility to ventricular and atrial arrhythmias.

Coordinated electrical activation of the heart is essential for the maintenance of a regular cardiac rhythm and effective contractions. Action potentials spread from one cell to the next via gap junction channels. Because of the elongated shape of cardiomyocytes, longitudinal resistivity is lower than transverse resistivity causing electrical anisotropy. Moreover, non-uniformity is created by clustering of gap junction channels at cell poles and by non-excitable structures such as collagenous strands, vessels or fibroblasts. Structural changes in cardiac disease often affect passive electrical properties by increasing non-uniformity and altering anisotropy. This disturbs normal electrical impulse propagation and is, consequently, a substrate for arrhythmia. However, to investigate how these structural changes lead to arrhythmias remains a challenge. One important mechanism, which may both cause and prevent arrhythmia, is the mismatch between current sources and sinks. Propagation of the electrical impulse requires a sufficient source of depolarizing current. In the case of a mismatch, the activated tissue (source) is not able to deliver enough depolarizing current to trigger an action potential in the non-activated tissue (sink). This eventually leads to conduction block. It has been suggested that in this situation a balanced geometrical distribution of gap junctions and reduced gap junction conductance may allow successful propagation. In contrast, source-sink mismatch can prevent spontaneous arrhythmogenic activity in a small number of cells from spreading over the ventricle, especially if gap junction conductance is enhanced. Beside gap junctions, cell geometry and non-cellular structures strongly modulate arrhythmogenic mechanisms. The present review elucidates these and other implications of passive electrical properties for cardiac rhythm and arrhythmogenesis.

Gold vs. platinum-iridium tip catheter for cavotricuspid isthmus ablation: the AURUM 8 study.

AIMS Gold electrodes have the theoretical advantage of creating bigger lesions than platinum-iridium (Pt-Ir) electrodes. We performed a prospective randomized study to compare the clinical efficacy of standard 8 mm Pt-Ir tip catheter (control) and 8 mm gold-tip catheters in the ablation of the cavotricuspid isthmus (CTI)-dependent atrial flutter. METHODS AND RESULTS A total of 463 patients undergoing CTI ablation in 19 clinical centres were randomized to receive the treatment by gold-tip or control catheter. The primary endpoint was cumulative radiofrequency (RF) application duration until achieving bidirectional CTI block. It did not differ significantly for the two catheters. The gold-tip catheter was, however, associated with a higher ablation success rate (94.3 vs. 89.0%, P = 0.042) and a substantially lower incidence of char and coagulum formation (4.8 vs. 37.9%, P < 0.001), which required exchange of 1 gold-tip (0.4%) and 10 control catheters (4.6%, P = 0.005). The gold-tip catheter delivered more mean power (52 ± 12 W) than the control catheter (48 ± 13 W, P < 0.001). Both mean and maximum temperatures measured by the thermocouple integrated in the catheter tip were statistically significantly lower in the gold (mean: 53.2 ± 4.7°C, max: 68.7 ± 6.6°C) than in the control catheter (54.3 ± 5.2 and 70.2 ± 7.0°C, respectively, P < 0.05). Fluoroscopy time, procedure duration, procedural-related complications, and arrhythmia recurrence during 6 months of follow-up did not differ between the two catheters. CONCLUSION Owing to a higher primary ablation success rate and reduced incidence of char/coagulum formation, gold may be preferred over Pt-Ir as electrode material for 8 mm tip catheters for CTI ablation. ClinicalTrials.gov: NCT00326001 (http://clinicaltrials.gov/ct2/show/NCT00326001).

Radiofrequency ablation of accessory pathways. Contemporary success rates and complications in 323 patients.

Das Ziel dieser Studie war es, 17 Jahre nach der ersten Hochfrequenzstrom (HF)-Katheterablation einer akzessorischen Bahn, die gegenwärtig erreichten Erfolgsraten der HF-Ablation akzessorischer Leitungsbahnen zusammen mit den Prozedurdaten und Komplikationsraten zu analysieren. Da bisherige Untersuchungen über die Lokalisation akzessorischer Leitungsbahnen noch auf der alten Nomenklatur basieren, war es ein weiteres Ziel, die Verteilung akzessorischer atrioventrikulärer Leitungsbahnen unter Gebrauch der 1999 von ESC und NASPE eingeführten neuen Nomenklatur zu analysieren. Es wurden die Daten aller Patienten, bei denen zwischen dem 1. 1. 2000 und dem 31. 12. 2003 am Herzzentrum Leipzig eine akzessorische Bahn abladiert wurde, retrospektiv analysiert. Über einen Zeitraum von 4 Jahren wurden an unserem Zentrum insgesamt 336 akzessorische Bahnen bei 323 Patienten abladiert. Gemäß der neuen Nomenklatur wurden die Bahnen eingeteilt in links gelegene, rechts gelegene, septale und paraseptale akzessorische Bahnen. 188 der Bahnen (56%) lagen links, 41 (12%) rechts, 64 (19%) (infero-)paraseptal und 31 (9%) septal oder parahissär. 12 Bahnen (4%) zeigten atypische Verläufe und/oder Eigenschaften und konnten somit nicht klar zugeordnet werden. Die mittlere Prozedurdauer betrug 68±37 Minuten. Die Erfolgsrate betrug insgesamt 98%. Bei 289 der Patienten (89%) konnte die akzessorische Bahn in einer einzigen Untersuchung erfolgreich abladiert werden. Komplikationen traten bei weniger als 2% der behandelten Patienten auf. 17 Jahre nach Durchführung der ersten HF-Katheterablation einer akzessorischen Leitungsbahn hat sich diese als hocheffektive und komplikationsarme kurative Behandlungsmethode etabliert. Die Erfolgsraten sind in den letzten 10 Jahren weiter gestiegen und die Komplikationsraten konnten weiter gesenkt werden. Mit der Einführung der neuen Nomenklatur ist es für den interventionellen Elektrophysiologen leichter geworden, die Lokalisation einer akzessorischen Bahn gemäß der realen anatomischen Lage im Körper festzulegen. 17 years ago the first radiofrequency catheter ablation of an accessory pathway (AP) was performed. The aim of this study was to describe the contemporary success rates and procedure related complication rates of radiofrequency (RF) ablation of accessory pathways (APs). In addition, the present study describes the anatomical distribution of APs according to the new nomenclature introduced by NASPE and ESC in 1999. The analysis included all patients, who underwent RF ablation of an AP in the Heart Center Leipzig between January 2000 and December 2003. Over a 4 year period 336 APs were ablated in 323 patients. 201 APs (60%) presented with antegrade and retrograde conduction and showed preexcitation on ECG. For the remaining 135 APs (40%), only retrograde conduction over the AP was documented. According to the new nomenclature APs were classified as left-sided, right sided, septal and paraseptal APs. 188 APs (56%) were located on the left, 41 (12%) on the right, 64 (19%) in the paraseptal space and 31 APs (9%) presented with a septal or parahissian localization, respectively. Because of atypical course and/or characteristics 12 APs (4%) could not be classified. Ablation of all pathways were successful in 315 patients (98%). In 289 patients (89%) success was achieved within a single ablation session. The left-sided pathways had a re-intervention rate of 5%, which was significantly lower compared to the remaining localizations. The highest re-intervention rate was observed in the septal APs (23%). Complications were observed in less than 2% of all treated patients. 17 years after the first RF catheter ablation of an AP this therapy is established as a highly effective procedure. The success rate has improved to 98% and the complication rate has been minimized to less than 2%. The most frequent localization of APs is left posterior. Left sided APs also presented with the lowest re-intervention rate. The introduction of the new nomenclature in 1999 by NASPE and ESC has simplified the description of the exact anatomical localization of an AP.