RIPPLE-VT study: Multicenter prospective evaluation of ventricular tachycardia substrate ablation by targeting scar channels to eliminate latest scar potentials without direct ablation.

BACKGROUND: Recurrent ventricular tachycardia (VT) can be treated by substrate modification of the myocardial scar by catheter ablation during sinus rhythm without VT induction. Better defining this arrhythmic substrate could help improve outcome and reduce ablation burden. OBJECTIVE: The study aimed to limit ablation within postinfarction scar to conduction channels within the scar to reduce VT recurrence. METHODS: Patients undergoing catheter ablation for recurrent implantable cardioverter-defibrillator therapy for postinfarction VT were recruited at 5 centers. Left ventricular maps were collected on CARTO using a Pentaray catheter. Ripple mapping was used to categorize infarct scar potentials (SPs) by timing. Earliest SPs were ablated sequentially until there was loss of the terminal SPs without their direct ablation. The primary outcome measure was sustained VT episodes as documented by device interrogations at 1 year, which was compared with VT episodes in the year before ablation. RESULTS: The study recruited 50 patients (mean left ventricular ejection fraction, 33% ± 9%), and 37 patients (74%) met the channel ablation end point with successful loss of latest SPs without direct ablation. There were 16 recurrences during 1-year follow-up. There was a 90% reduction in VT burden from 30.2 ± 53.9 to 3.1 ± 7.5 (P < .01) per patient, with a concomitant 88% reduction in appropriate shocks from 2.1 ± 2.7 to 0.2 ± 0.9 (P < .01). There were 8 deaths during follow-up. Those who met the channel ablation end point had no significant difference in mortality, recurrence, or VT burden but had a significantly lower ablation burden of 25.7 ± 4.2 minutes vs 39.9 ± 6.1 minutes (P = .001). CONCLUSION: Scar channel ablation is feasible by ripple mapping and can be an alternative to more extensive substrate modification techniques.

Characterization of conduction system activation in the postinfarct ventricle using ripple mapping.

BACKGROUND: Three-dimensional (3D) mapping of the ventricular conduction system is challenging. OBJECTIVE: The purpose of this study was to use ripple mapping to distinguish conduction system activation to that of adjacent myocardium in order to characterize the conduction system in the postinfarct left ventricle (LV). METHODS: High-density mapping (PentaRay, CARTO) was performed during normal rhythm in patients undergoing ventricular tachycardia ablation. Ripple maps were viewed from the end of the P wave to QRS onset in 1-ms increments. Clusters of >3 ripple bars were interrogated for the presence of Purkinje potentials, which were tagged on the 3D geometry. Repeating this process allowed conduction system delineation. RESULTS: Maps were reviewed in 24 patients (mean 3112 ± 613 points). There were 150.9 ± 24.5 Purkinje potentials per map, at the left posterior fascicle (LPF) in 22 patients (92%) and at the left anterior fascicle (LAF) in 15 patients (63%). The LAF was shorter (41.4 vs 68.8 mm; P = .0005) and activated for a shorter duration (40.6 vs 64.9 ms; P = .002) than the LPF. Fourteen of 24 patients had left bundle branch block (LBBB), with 11 of 14 (78%) having Purkinje potential-associated breakout. There were fewer breakouts from the conduction system during LBBB (1.8 vs 3.4; 1.6 ± 0.6; P = .039) and an inverse correlation between breakout sites and QRS duration (P = .0035). CONCLUSION: We applied ripple mapping to present a detailed electroanatomic characterization of the conduction system in the postinfarct LV. Patients with broader QRS had fewer LV breakout sites from the conduction system. However, there was 3D mapping evidence of LV breakout from an intact conduction system in the majority of patients with LBBB.

High-resolution mapping of the circuit of typical atrioventricular nodal reentrant tachycardia.

BACKGROUND: Recent anatomic and electrophysiologic evidence has provided new insight into the anatomic substrate. Previous reports on electroanatomic mapping (EAM) of the circuit of atrioventricular nodal reentrant tachycardia (AVNRT) have been limited by mapping only the triangle of Koch on the right side of the septum and by the use of conventional mapping tools. The objectives are to obtain comprehensive high-resolution mapping of typical AVNRT and to investigate the role of the atrioventricular ring tissues in the circuit. METHODS: We employed EAM with the use of novel modules and algorithms for studying typical AVNRT from the right and the left sides of the septum. RESULTS: We performed extensive mapping of both the atrial septum and the septal vestibule of the tricuspid valve during typical AVNRT in 9 (6 females) patients, aged 49.6 ± 12.1 years. In two of these, left septal mapping was also obtained through the aorta. The earliest initial activation was variable, emanating from the superior or medial septum. The impulse consistently appeared below the orifice of the coronary sinus, at the site where its inferoanterior margin merged with the septal vestibule of the tricuspid valve at its entrance to the right atrium. It then returned to the initial activation site, presumably through the septal vestibular myocardium. The left septal activation area corresponded to that recorded on the right side. CONCLUSIONS: Typical AVNRT uses a circuit confined within the pyramid of Koch from the AV node to the septal isthmus, involving the myocardial walls of the pyramidal space.

Catheter Ablation for Ventricular Tachycardia After MI: A Reconstructed Individual Patient Data Meta-analysis of Randomised Controlled Trials.

Background: The prognostic impact of ventricular tachycardia (VT) catheter ablation is an important outstanding research question. We undertook a reconstructed individual patient data meta-analysis of randomised controlled trials comparing ablation to medical therapy in patients developing VT after MI. Methods: We systematically identified all trials comparing catheter ablation to medical therapy in patients with VT and prior MI. The prespecified primary endpoint was reconstructed individual patient assessment of all-cause mortality. Prespecified secondary endpoints included trial-level assessment of all-cause mortality, VT recurrence or defibrillator shocks and all-cause hospitalisations. Prespecified subgroup analysis was performed for ablation approaches involving only substrate modification without VT activation mapping. Sensitivity analyses were performed depending on the proportion of patients with prior MI included. Results: Eight trials, recruiting a total of 874 patients, were included. Of these 874 patients, 430 were randomised to catheter ablation and 444 were randomised to medical therapy. Catheter ablation reduced all-cause mortality compared with medical therapy when synthesising individual patient data (HR 0.63; 95% CI [0.41-0.96]; p=0.03), but not in trial-level analysis (RR 0.91; 95% CI [0.67-1.23]; p=0.53; I2=0%). Catheter ablation significantly reduced VT recurrence, defibrillator shocks and hospitalisations compared with medical therapy. Sensitivity analyses were consistent with the primary analyses. Conclusion: In patients with postinfarct VT, catheter ablation reduces mortality.

Ripple AT Plus - isthmus-guided vs conventional ablation in the treatment of scar-related atrial tachycardia: study protocol for a randomised controlled trial.

BACKGROUND: Catheter ablation is routinely used to treat scar-related atrial tachycardia (s-AT). Conventional ablation often involves creating anatomical "lines" that transect myocardial tissue supporting reentry. This can be extensive, creating iatrogenic scar as a nidus for future reentry, and may account for arrhythmia recurrence. High-density mapping may identify "narrower isthmuses" requiring less ablation, with ripple mapping proven to be an effective approach in identifying. This trial explores whether ablation of narrower isthmuses in s-AT, defined using ripple mapping, results in greater freedom from arrhythmia recurrence compared to conventional ablation. METHODS: The Ripple-AT-Plus trial (registration ClinicalTrials.gov , NCT03915691) is a prospective, multicentre, single-blinded, randomised controlled trial with 12-month follow-up. Two hundred s-AT patients will be randomised in a 1:1 fashion to either "ripple mapping-guided isthmus ablation" vs conventional ablation on the CARTO3 ConfiDENSE system (Biosense Webster). The primary outcome will compare recurrence of any atrial arrhythmia. Multicentre data will be analysed over a secure web-based cloud-storage and analysis software (CARTONETTM). CONCLUSION: This is the first trial that considers long-term patient outcomes post s-AT ablation, and whether targeting narrower isthmuses in the era of high density is optimal.

A randomized controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalized with COVID-19: the COVID-19 Acute Coronary Syndrome trial.

BACKGROUND: Patients hospitalized with COVID-19 suffer thrombotic complications. Risk factors for poor outcomes are shared with coronary artery disease. OBJECTIVES: To investigate the efficacy of an acute coronary syndrome regimen in patients hospitalized with COVID-19 and coronary disease risk factors. METHODS: A randomized controlled, open-label trial across acute hospitals (United Kingdom and Brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28 days. Primary efficacy and safety outcomes were 30-day mortality and bleeding. The key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, or death). RESULTS: Three hundred twenty patients from 9 centers were randomized. The trial terminated early due to low recruitment. At 30 days, there was no significant difference in mortality (intervention vs control, 11.5% vs 15%; unadjusted odds ratio [OR], 0.73; 95% CI, 0.38-1.41; p = .355). Significant bleeds were infrequent and were not significantly different between the arms (intervention vs control, 1.9% vs 1.9%; p > .999). Using a Bayesian Markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (OR, 1.46; 95% credible interval [CrI], 0.88-2.37; Pr [beta > 0], 93%; adjusted OR, 1.50; 95% CrI, 0.91-2.45; Pr [beta > 0], 95%) and median time to discharge to home was 2 days shorter (95% CrI, -4 to 0; 2% probability that it was worse). CONCLUSION: Acute coronary syndrome treatment regimen was associated with a reduction in the length of hospital stay without an excess in major bleeding. A larger trial is needed to evaluate mortality.

A randomized controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalized with COVID-19: the COVID-19 Acute Coronary Syndrome trial

BACKGROUND: patients hospitalised with covid-19 suffer thrombotic complications. risk factors for poor outcomes are shared with coronary artery disease. Objectives: to investigate efficacy of an acute coronary syndrome regimen in patients hospitalised with covid-19 and coronary disease risk factors. PATIENTS/METHODS: a randomised controlled open-label trial across acute hospitals (uk and brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28-days. primary efficacy and safety outcomes were 30-day mortality and bleeding. the key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, death). RESULTS: 320 patients from 9 centres were randomised. the trial terminated early due to low recruitment. at 30 days there was no significant difference in mortality (intervention: 11.5% vs control: 15%, unadjusted or 0.73, 95%ci 0.38 to 1.41, p=0.355). significant bleeds were infrequent and not significantly different between the arms (intervention: 1.9% vs control 1.9%, p>0.999). using a bayesian markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (or 1.46, 95% cri 0.88 to 95 2.37, pr(beta>0) =93%; adjusted or 1.50, 95% cri 0.91 to 2.45, pr(beta>0) =95%) and median time to discharge home was two days shorter (95% cri -4 to 0, 2% probability that it was worse). CONCLUSIONS: acute coronary syndrome treatment regimen was associated with a 99 reduction in the length of hospital stay without an excess in major bleeding. a larger trial is needed to evaluate mortality.

Spatial characterization of the tachycardia circuit of atrioventricular nodal re-entrant tachycardia.

AIMS: The exact circuit of atrioventricular nodal re-entrant tachycardia (AVNRT) remains elusive. To assess the location and dimensions of the AVNRT circuit. METHODS AND RESULTS: Both typical and atypical AVNRT were induced at electrophysiology study of 14 patients. We calculated the activation time of the fast and slow pathways, and consequently, the length of the slow pathway, by assuming an average conduction velocity of 0.04 mm/ms in the nodal area. The distance between the compact atrioventricular node and the slow pathway ablating electrode was measured on three-dimensionally reconstructed fluoroscopic images obtained in diastole and systole. We also measured the length of the histologically discrete right inferior nodal extension in 31 human hearts. The length of the slow pathway was calculated to be 10.8 ± 1.3 mm (range 8.2-12.8 mm). The distance from the node to the ablating electrode was measured in five patients 17.0 ± 1.6 mm (range 14.9-19.2 mm) and was consistently longer than the estimated length of the slow pathway (P < 0.001). The length of the right nodal inferior extension in histologic specimens was 8.1 ± 2.3 mm (range 5.3-13.7 mm). There were no statistically significant differences between these values and the calculated slow pathway lengths. CONCLUSION: Successful ablation affects the tachycardia circuit without necessarily abolishing slow conduction, probably by interrupting the circuit at the septal isthmus.

Postinfarct ventricular tachycardia substrate: Characterization and ablation of conduction channels using ripple mapping.

BACKGROUND: Conduction channels have been demonstrated within the postinfarct scar and seem to be co-located with the isthmus of ventricular tachycardia (VT). Mapping the local scar potentials (SPs) that define the conduction channels is often hindered by large far-field electrograms generated by healthy myocardium. OBJECTIVE: The purpose of this study was to map conduction channel using ripple mapping to categorize SPs temporally and anatomically. We tested the hypothesis that ablation of early SPs would eliminate the latest SPs without direct ablation. METHODS: Ripple maps of postinfarct scar were collected using the PentaRay (Biosense Webster) during normal rhythm. Maps were reviewed in reverse, and clusters of SPs were color-coded on the geometry, by timing, into early, intermediate, late, and terminal. Ablation was delivered sequentially from clusters of early SPs, checking for loss of terminal SPs as the endpoint. RESULTS: The protocol was performed in 11 patients. Mean mapping time was 65 ± 23 minutes, and a mean 3050 ± 1839 points was collected. SP timing ranged from 98.1 ± 60.5 ms to 214.8 ± 89.8 ms post QRS peak. Earliest SPs were present at the border, occupying 16.4% of scar, whereas latest SPs occupied 4.8% at the opposing border or core. Analysis took 15 ± 10 minutes to locate channels and identify ablation targets. It was possible to eliminate latest SPs in all patients without direct ablation (mean ablation time 16.3 ± 11.1 minutes). No VT recurrence was recorded (mean follow-up 10.1 ± 7.4 months). CONCLUSION: Conduction channels can be located using ripple mapping to analyze SPs. Ablation at channel entrances can eliminate the latest SPs and is associated with good medium-term results.

Electroanatomic Characterization and Ablation of Scar-Related Isthmus Sites Supporting Perimitral Flutter.

OBJECTIVES: The authors reviewed 3-dimensional electroanatomic maps of perimitral flutter to identify scar-related isthmuses and determine their effectiveness as ablation sites. BACKGROUND: Perimitral flutter is usually treated by linear ablation between the left lower pulmonary vein and mitral annulus. Conduction block can be difficult to achieve, and recurrences are common. METHODS: Patients undergoing atrial tachycardia ablation using CARTO3 (Biosense Webster Inc., Irvine, California) were screened from 4 centers. Patients with confirmed perimitral flutter were reviewed for the presence of scar-related isthmuses by using CARTO3 with the ConfiDense and Ripple Mapping modules. RESULTS: Confirmed perimitral flutter was identified in 28 patients (age 65.2 ± 8.1 years), of whom 26 patients had prior atrial fibrillation ablation. Scar-related isthmus ablation was performed in 12 of 28 patients. Perimitral flutter was terminated in all following correct identification of a scar-related isthmus using ripple mapping. The mean scar voltage threshold was 0.11 ± 0.05 mV. The mean width of scar-related isthmuses was 8.9 ± 3.5 mm with a conduction speed of 31.8 ± 5.5 cm/s compared to that of normal left atrium of 71.2 ± 21.5 cm/s (p < 0.0001). Empirical, anatomic ablation was performed in 16 of 28, with termination in 10 of 16 (63%; p = 0.027). Significantly less ablation was required for critical isthmus ablation compared to empirical linear lesions (11.4 ± 5.3 min vs. 26.2 ± 17.1 min; p = 0.0004). All 16 cases of anatomic ablation were reviewed with ripple mapping, and 63% had scar-related isthmus. CONCLUSIONS: Perimitral flutter is usually easy to diagnose but can be difficult to ablate. Ripple mapping is highly effective at locating the critical isthmus maintaining the tachycardia and avoiding anatomic ablation lines. This approach has a higher termination rate with less radiofrequency ablation required.

How achievable are COVID-19 clinical trial recruitment targets? A UK observational cohort study and trials registry analysis.

OBJECTIVES: To analyse enrolment to interventional trials during the first wave of the COVID-19 pandemic in England and describe the barriers to successful recruitment in the circumstance of a further wave or future pandemics. DESIGN: We analysed registered interventional COVID-19 trial data and concurrently did a prospective observational study of hospitalised patients with COVID-19 who were being assessed for eligibility to one of the RECOVERY, C19-ACS or SIMPLE trials. SETTING: Interventional COVID-19 trial data were analysed from the clinicaltrials.gov and International Standard Randomized Controlled Trial Number databases on 12 July 2020. The patient cohort was taken from five centres in a respiratory National Institute for Health Research network. Population and modelling data were taken from published reports from the UK government and Medical Research Council Biostatistics Unit. PARTICIPANTS: 2082 consecutive admitted patients with laboratory-confirmed SARS-CoV-2 infection from 27 March 2020 were included. MAIN OUTCOME MEASURES: Proportions enrolled, and reasons for exclusion from the aforementioned trials. Comparisons of trial recruitment targets with estimated feasible recruitment numbers. RESULTS: Analysis of trial registration data for COVID-19 treatment studies enrolling in England showed that by 12 July 2020, 29 142 participants were needed. In the observational study, 430 (20.7%) proceeded to randomisation. 82 (3.9%) declined participation, 699 (33.6%) were excluded on clinical grounds, 363 (17.4%) were medically fit for discharge and 153 (7.3%) were receiving palliative care. With 111 037 people hospitalised with COVID-19 in England by 12 July 2020, we determine that 22 985 people were potentially suitable for trial enrolment. We estimate a UK hospitalisation rate of 2.38%, and that another 1.25 million infections would be required to meet recruitment targets of ongoing trials. CONCLUSIONS: Feasible recruitment rates, study design and proliferation of trials can limit the number, and size, that will successfully complete recruitment. We consider that fewer, more appropriately designed trials, prioritising cooperation between centres would maximise productivity in a further wave.

Ripple-AT Study: A Multicenter and Randomized Study Comparing 3D Mapping Techniques During Atrial Tachycardia Ablations.

BACKGROUND: Ripple mapping (RM) is an alternative approach to activation mapping of atrial tachycardia (AT) that avoids electrogram annotation. We tested whether RM is superior to conventional annotation based local activation time (LAT) mapping for AT diagnosis in a randomized and multicenter study. METHODS: Patients with AT were randomized to either RM or LAT mapping using the CARTO3v4 CONFIDENSE system. Operators determined the diagnosis using the assigned 3D mapping arm alone, before being permitted a single confirmatory entrainment manuever if needed. A planned ablation lesion set was defined. The primary end point was AT termination with delivery of the planned ablation lesion set. The inability to terminate AT with this first lesion set, the use of more than one entrainment manuever, or the need to crossover to the other mapping arm was defined as failure to achieve the primary end point. RESULTS: One hundred five patients from 7 centers were recruited with 22 patients excluded due to premature AT termination, noninducibility or left atrial appendage thrombus. Eighty-three patients (pts; RM=42, LAT=41) completed mapping and ablation within the 2 groups of similar characteristics (RM versus LAT: prior ablation or cardiac surgery n=35 [83%] versus n=35 [85%], P=0.80). The primary end point occurred in 38/42 pts (90%) in the RM group and 29/41pts (71%) in the LAT group (P=0.045). This was achieved without any entrainment in 31/42 pts (74%) with RM and 18/41 pts (44%) with LAT (P=0.01). Of those patients who failed to achieve the primary end point, AT termination was achieved in 9/12 pts (75%) in the LAT group following crossover to RM with entrainment, but 0/4 pts (0%) in the RM group crossing over to LAT mapping with entrainment (P=0.04). CONCLUSIONS: RM is superior to LAT mapping on the CARTO3v4 CONFIDENSE system in guiding ablation to terminate AT with the first lesion set and with reduced entrainment to assist diagnosis. CLINICAL TRIALS REGISTRATION: https://www.clinicaltrials.gov. Unique identifier: NCT02451995.

Lesson of the month 1: A rare adverse reaction between flucloxacillin and paracetamol.

Flucloxacillin, a beta-lactam antibiotic, is a commonly prescribed antibiotic for the treatment of infections caused by staphylococci and streptococci, most notably Staphylococcus aureus Paracetamol is one of the most dispensed medications by NHS England and is used for the treatment of fever and pain.1 However most doctors are unaware that concurrent use of these drugs can cause a potentially fatal drug interaction due to pyroglutamic acidosis (PGA), also known as 5-oxoprolinaemia. PGA is a rare cause of raised anion gap metabolic acidosis due to disruption of the γ-glutamyl cycle. We report the case of a patient with multiple comorbidities who developed PGA due to coadministration of paracetamol and flucloxacillin.

Arrhythmia Mechanisms Revealed by Ripple Mapping.

Ripple mapping is a novel method of 3D intracardiac electrogram visualisation that allows activation of the myocardium to be tracked visually without prior assignment of local activation times and without interpolation into unmapped regions. It assists in the identification of tachycardia mechanism and optimal ablation site, without the need for an experienced computer-operating assistant. This expert opinion presents evidence demonstrating the benefit of Ripple Mapping, compared with traditional electroanatomic mapping techniques, for the diagnosis and management of atrial and ventricular tachyarrhythmias during electrophysiological procedures.

Coronary artery ectasia in Crohn's disease.

Coronary artery ectasia (CAE) can be ascribed, in the majority of cases, to coronary atherosclerosis. Nevertheless, the presence of isolated ectatic lesions without obstructive coronary artery disease and the association of CAE with several autoimmune diseases characterised by systemic vascular involvement suggest that the pathogenesis of CAE may extend beyond coronary atherosclerosis. We herein report the case of a 56-year-old male patient with Crohn's disease and isolated CAE, who has been found positive for IgM and IgA antiendothelial cell antibodies, and discuss a potential pathogenic mechanism.

Left Septal Slow Pathway Ablation for Atrioventricular Nodal Reentrant Tachycardia.

BACKGROUND: Immunohistochemistry studies suggest that the anatomic substrate of the slow pathway in atrioventricular nodal reentrant tachycardia (AVNRT) is the left inferior nodal extension. We hypothesized that slow pathway ablation from the left septum is an effective alternative to right-sided ablation. METHODS AND RESULTS: We analyzed our databases of AVNRT in search of cases that had used slow pathway ablation from the left septum because of failure of right septal ablation, and then prospectively subjected consenting patients to a left septal-only procedure. Of 1342 patients subjected to right septal slow pathway ablation for AVNRT, 15 patients, 11 with typical and 4 with atypical AVNRT, had a left septal approach after unsuccessful right-sided ablation (R+L group). Eleven patients were subjected to a left septal-only approach for slow pathway ablation without a previous right septal attempt (L group). Fluoroscopy times in the R+L and L groups were 30.5 (21.0-44.0) and 20.0 (17.0-25.0) minutes, respectively (P=0.061), and radiofrequency current delivery times were 11.3 (5.0-19.1) and 10.0 (7.0-12.0) minutes, respectively (P=0.897). There was no need for additional ablation lesions at other anatomic sites in either group, and no cases of atrioventricular block were encountered. Recurrence rates of the arrhythmia for the R+L and L groups were 6.7% and 0%, respectively, in the 3 months after ablation (P=1.000). CONCLUSIONS: Left septal ablation at the anatomic site of the left inferior nodal extension is an alternative for ablation of both typical and atypical AVNRT when ablation at the right posterior septum is ineffective.

Catheter ablation vs. antiarrhythmic drug therapy in patients with symptomatic atrioventricular nodal re-entrant tachycardia: a randomized, controlled trial.

AIMS: To conduct a randomized trial in order to guide the optimum therapy of symptomatic atrioventricular nodal re-entrant tachycardia (AVNRT). METHODS AND RESULTS: Patients with at least one symptomatic episode of tachycardia per month and an electrophysiologic diagnosis of AVNRT were randomly assigned to catheter ablation or chronic antiarrhythmic drug (AAD) therapy with bisoprolol (5 mg od) and/or diltiazem (120-300 mg od). All patients were properly educated to treat subsequent tachycardia episodes with autonomic manoeuvres or a 'pill in the pocket' approach. The primary endpoint of the study was hospital admission for persistent tachycardia cardioversion, during a follow-up period of 5 years. Sixty-one patients were included in the study. In the ablation group, 1 patient was lost to follow-up, and 29 were free of arrhythmia or conduction disturbances at a 5-year follow-up. In the AAD group, three patients were lost to follow-up. Of the remainder, 10 patients (35.7%) continued with initial therapy, 11 patients (39.2%) remained on diltiazem alone, and 7 patients (25%) interrupted their therapy within the first 3 months following randomization, and subsequently developed an episode requiring cardioversion. During a follow-up of 5 years, 21 patients in the AAD group required hospital admission for cardioversion. Survival free from the study endpoint was significantly higher in the ablation group compared with the AAD group (log-rank test, P < 0.001). CONCLUSIONS: Catheter ablation is the therapy of choice for symptomatic AVNRT. Antiarrhythmic drug therapy is ineffective and not well tolerated.

Management of Complications in Anticoagulated Patients with Atrial Fibrillation.

Oral anticoagulation is mandatory for patients at high risk of thromboembolism, but the risk of bleeding should also be taken into account. Direct oral anticoagulants are now recommended for non-valvular AF as a potential alternative to warfarin. In this article we discuss methods to assess the anticoagulant effect of these agents, specific and general antidotes, and management of complications such as embolic and haemorrhagic stroke, and significant bleeding.