Novel Approaches for the Diagnosis of Concealed Nodo-Ventricular and His-Ventricular Pathways.

BACKGROUND: Confirming the presence and participation of concealed nodo-ventricular (cNV) or concealed His-ventricular (cHV) pathways in tachyarrhythmias is challenging. We describe novel observations to aid in diagnosing cNV or cHV pathways. METHODS: We present 7 cases of cNV and cHV pathway-mediated arrhythmias and focus on several laboratory observations: (1) differential ventricular overdrive pacing (VOD) from the base versus apex, (2) response to His refractory premature ventricular complexes, (3) paradoxical atriohisian response (shorter atriohisian interval during tachycardia than that during sinus rhythm) in long RP tachycardia, and (4) the role of adenosine to aid in the diagnosis. RESULTS: Three cases underwent differential VOD during tachycardia. All demonstrated a shorter postpacing interval minus tachycardia cycle length during basal pacing than apical pacing with one case exhibiting apical VOD results compatible with atrioventricular nodal reentrant tachycardia. Basal VOD was useful for localizing the ventricular connection in a case with cHV pathway. In 3 cases, His refractory premature ventricular complexes reset the tachycardia without conduction to the atrium, which excluded the involvement of an atrioventricular pathway or atrial tachycardia, or atrioventricular nodal reentrant tachycardia alone. One case had His refractory premature ventricular complexes followed by subsequent constant AA interval and then tachycardia termination, suggesting a bystander cNV pathway involvement. Two cNV pathway cases presented with long RP tachycardia had paradoxical atriohisian shortening of >15 ms, suggesting parallel activation of the atrium and the atrioventricular node. Adenosine terminated the tachycardia with retrograde block in 2 cases with cNV pathways but had no response on a cHV pathway. CONCLUSIONS: cNV and cHV pathways mediated tachyarrhythmias can present with variable clinical presentations. We emphasize the important role of differential VOD sites, His refractory premature ventricular complexes that reset or terminate the tachycardia without conduction to the atrium, paradoxical atriohisian response in long RP tachycardia, and the use of adenosine for diagnosing cNV and cHV pathways.

Red Flags in Syncope: Clues for the Diagnosis of Idiopathic Ventricular Fibrillation.

Idiopathic ventricular fibrillation is responsible for ≈5%-7% of aborted cardiac arrest, mainly striking subjects in their forties. Syncope caused by short-coupled rapid polymorphic ventricular tachycardia is frequently noted in a patient's past history. However, a diagnosis of neurally mediated syncope, the most frequent cause of syncope in the young, is often erroneously made. Clinical clues suggest that syncope has an arrhythmic rather than a neurally mediated origin. In addition, the presence of premature ventricular contractions on an electrocardiogram recorded shortly after a syncopal event has utmost importance in establishing the cause of syncope. Although such extrasystoles are frequently benign, especially when associated with a long coupling interval, they also may suggest a malignant origin when closely coupled to the preceding complex with short coupling intervals (usually <350 ms). These arrhythmias mainly originate from the Purkinje system (usually the right ventricle in men and the left ventricle in women) and favorably respond to quinidine as well as to ablation therapy targeting Purkinje-fibers ectopic activity.

Short-Coupled Idiopathic Ventricular Fibrillation: A Literature Review With Extended Follow-Up.

Idiopathic ventricular fibrillation is responsible for approximately 5%-7% of cases of aborted cardiac arrest. Recent studies have shown that short-coupled ventricular premature complexes are present at the onset of idiopathic ventricular fibrillation in 6.6%-17% of patients. The present review provided information on 86 patients with short-coupled malignant ventricular arrhythmias that were reported as case reports or small patient series during the last 70 years. In 75% of the 81 cases published during the last 40 years, extended information and follow-up (from 2.63 ± 4.5 years to 10.67 ± 7.8 years; P < 0.001, between the original publication to the latest update) could be obtained from the authors. The review shows that short-coupled malignant ventricular arrhythmias occurred almost equally in males and females, at the mean age of 40 years. A tendency for later occurrence of the arrhythmia by 4 years was observed in females. A prior history of syncope was noted in 45.3% of the patients, whereas arrhythmic storm occurred in 42% at presentation. The most common mode of revelation of short-coupled malignant ventricular arrhythmias was syncope (53.5%), followed by aborted cardiac arrest (26.7%) and recurrent arrhythmic event after prior implantable-cardioverter defibrillator implantation for idiopathic ventricular fibrillation (17.4%). For the first time, short-coupled malignant arrhythmias exhibiting "not-so-short" coupling intervals (≥350 milliseconds) were found in a significant proportion of patients (17.4%). During long-term follow-up, quinidine yielded a slightly higher success rate in arrhythmia control than ablation. Larger studies are necessary to assess the best strategy for the management of this potentially lethal arrhythmia.

The prevalence of left and right bundle branch block morphology ventricular tachycardia amongst patients with arrhythmogenic cardiomyopathy and sustained ventricular tachycardia: insights from the European Survey on Arrhythmogenic Cardiomyopathy.

AIMS: In arrhythmogenic cardiomyopathy (ACM), sustained ventricular tachycardia (VT) typically displays a left bundle branch block (LBBB) morphology while a right bundle branch block (RBBB) morphology is rare. The present study assesses the VT morphology in ACM patients with sustained VT and their clinical and genetic characteristics. METHODS AND RESULTS: Twenty-six centres from 11 European countries provided information on 954 ACM patients who had ≥1 episode of sustained VT spontaneously documented during patients' clinical course. Arrhythmogenic cardiomyopathy was defined according to the 2010 Task Force Criteria, and VT morphology according to the QRS pattern in V1. Overall, 882 (92.5%) patients displayed LBBB-VT alone and 72 (7.5%) RBBB-VT [alone in 42 (4.4%) or in combination with LBBB-VT in 30 (3.1%)]. Male sex prevalence was 79.3%, 88.1%, and 56.7% in the LBBB-VT, RBBB-VT, and LBBB + RBBB-VT groups, respectively (P = 0.007). First RBBB-VT occurred 5 years after the first LBBB-VT (46.5 ± 14.4 vs 41.1 ± 15.8 years, P = 0.011). An implanted cardioverter-defibrillator was more frequently implanted in the RBBB-VT (92.9%) and the LBBB + RBBB-VT groups (90%) than in the LBBB-VT group (68.1%) (P < 0.001). Mutations in PKP2 predominated in the LBBB-VT (65.2%) and the LBBB + RBBB-VT (41.7%) groups while DSP mutations predominated in the RBBB-VT group (45.5%). By multivariable analysis, female sex was associated with LBBB + RBBB-VT (P = 0.011) while DSP mutations were associated with RBBB-VT (P < 0.001). After a median follow-up of 103 (51-185) months, death occurred in 106 (11.1%) patients with no intergroup difference (P = 0.176). CONCLUSION: RBBB-VT accounts for a significant proportion of sustained VTs in ACM. Sex and type of pathogenic mutations were associated with VT type, female sex with LBBB + RBBB-VT, and DSP mutation with RBBB-VT.

Use of New Imaging CARTO® Segmentation Module Software to Facilitate Ablation of Ventricular Arrhythmias.

INTRODUCTION: A new imaging software (CARTO® Segmentation Module, Biosense Webster) allows preprocedural 3-D reconstruction of all heart chambers based on cardiac CT. We describe our initial experience with the new module during ablation of ventricular arrhythmias. METHODS AND RESULTS: Eighteen consecutive patients with idiopathic ventricular arrhythmias or ischemic ventricular tachycardia (VT) were studied. In the latter group, a combined endocardial and epicardial ablation was performed. Of the 14 patients with idiopathic arrhythmias, 12 were ablated in the outflow tract (OT), 1 in the midseptal left ventricle, and 1 at the left posterior fascicular area; acute successful ablation was achieved in 11 (78.6%) patients. The procedure was discontinued due to close proximity of the arrhythmia origin to the coronary arteries (CA) in 2 patients. Acute successful uncomplicated ablation was achieved in all 4 patients with ischemic VT. During ablation in the coronary cusps commissures, the CARTO® Segmentation Module accurately defined the cusps anatomy. The precise anatomic location provided by the module assisted in successfully ablating when information from activation mapping was not optimal, by ablating at the opposite side of the cusps. In addition, by demonstrating the precise location of the CA, it allowed safe ablation of arrhythmias that originated in close proximity to the CA both in the OT area and the epicardium, eliminating the need for repeat angiography. CONCLUSIONS: The CARTO® Segmentation Module is useful for accurate definition of the exact anatomic location of ventricular arrhythmias and for safely ablating them especially in close proximity to the CA.

Drug-induced Brugada syndrome: Clinical characteristics and risk factors.

BACKGROUND: Cardiac arrest may result from seemingly innocuous medications that do not necessarily have cardiac indications. The best-known example is the drug-induced long QT syndrome. A less known but not necessarily less important form of drug-induced proarrhythmia is the drug-induced Brugada syndrome. OBJECTIVE: The purpose of this study was to identify clinical and ECG risk markers for drug-induced Brugada syndrome. METHODS: Reports of drug-induced Brugada syndrome recounted by an international database (http://www.brugadadrugs.org) were reviewed to define characteristics that identify patients prone to developing this complication. For each patient with drug-induced Brugada syndrome who had an ECG recorded in the absence of drugs, we included 5 healthy controls matched by gender and age. All ECGs were evaluated for Brugada-like abnormalities. RESULTS: Seventy-four cases of drug-induced Brugada syndrome from noncardiac medications were identified: 77% were male, and drug toxicity was involved in 46%. Drug-induced Brugada syndrome from oral medications generally occurred weeks after the initiation of therapy. Mortality was 13%. By definition, all cases had a type I Brugada pattern during drug therapy. Nevertheless, their ECG in the absence of drugs was more frequently abnormal than the ECG of controls (56% vs 33%, P = .04). CONCLUSION: Drug-induced Brugada syndrome from noncardiac drugs occurs predominantly in adult males, is frequently due to drug toxicity, and occurs late after the onset of therapy. Minor changes are frequently noticeable on baseline ECG, but screening is impractical because of a prohibitive false-positive rate.

Effects of sex on the incidence of cardiac tamponade after catheter ablation of atrial fibrillation: results from a worldwide survey in 34 943 atrial fibrillation ablation procedures.

BACKGROUND: Cardiac tamponade is the most dramatic complication observed during atrial fibrillation (AF) ablation and the leading cause of procedure-related mortality. Female sex is a known risk factor for complications during AF ablation; however, it is unknown whether women have a higher risk of tamponade. METHODS AND RESULTS: A systematic Medline search was used to locate academic electrophysiological centers that reported cases of tamponade occurring during AF ablation. Centers were asked to provide information on cases of acute tamponade according to sex and their mode of management including any case of related mortality. Nineteen electrophysiological centers provided information on 34 943 ablation procedures involving 25 261 (72%) men. Overall, 289 (0.9%) cases of tamponade were reported: 120 (1.24%) in women and 169 (0.67%) in men (odds ratio, 1.83; P<0.001). There was a reciprocal association between center volume and the occurrence of tamponade with substantially lower risk in high-volume centers. Most cases of tamponade occurred during catheter manipulation or ablation; women tended to develop more tamponades during transseptal catheterization. No sex difference in the mode of management was observed. However, 16% cases of tamponade required surgery with lower rates in high-volume centers. Three cases of tamponade (1%) culminated in death. CONCLUSIONS: Tamponade during AF ablation procedures is relatively rare. Women have an ≈2-fold higher risk for developing this complication. The risk of tamponade among women decreases substantially in high-volume centers. Surgical backup and acute management skills for treating tamponade are important in centers performing AF ablation.

Distinguishing "benign" from "malignant early repolarization": the value of the ST-segment morphology.

BACKGROUND: Means for distinguishing the very common "benign early repolarization" from the very rare but malignant form are needed. Recently, the presence of early repolarization with "horizontal ST segment" was found to predict arrhythmic death during long-term follow-up in a large population study. We therefore speculated that the combination of "J waves with horizontal ST segment" would correlate with a history of idiopathic ventricular fibrillation (VF) better than the mere presence of J waves. OBJECTIVES: To determine whether the morphology of the ST segment adds diagnostic value to the mere presence of J waves in a case-control series of idiopathic VF. METHODS: We reanalyzed our case-control study showing that the presence of J waves strongly correlates with a history of idiopathic VF among 45 patients with this disorder, 124 controls matched for age and gender ("matched-control" group), and 121 young athletes. This time we focused only on those patients with J waves and graded their ST-segment morphology as either "horizontal" or "ascending" according to predefined criteria. RESULTS: The presence of J waves was associated with a history of idiopathic VF with an odds ratio of 4.0 (95% confidence intervals = 2.0-7.9), but having both J waves and horizontal ST segment yielded an odds ratio of 13.8 (95% confidence intervals = 5.1-37.2) for having idiopathic VF. CONCLUSIONS: We report, for the first time, that the combination of J waves with horizontal/descending ST segment improved our ability to distinguish patients with idiopathic VF from controls matched by gender and age.

Postpacing abnormal repolarization in catecholaminergic polymorphic ventricular tachycardia associated with a mutation in the cardiac ryanodine receptor gene.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease for which electrophysiological studies (EPS) have shown to be of limited value. OBJECTIVE: This study presents a CPVT family in which marked postpacing repolarization abnormalities during EPS were the only consistent phenotypic manifestation of ryanodine receptor (RyR2) mutation carriers. METHODS: The study was prompted by the observation of transient marked QT prolongation preceding initiation of ventricular fibrillation during atrial fibrillation in a boy with a family history of sudden cardiac death (SCD). Family members underwent exercise and pharmacologic electrocardiographic testing with epinephrine, adenosine, and flecainide. Noninvasive clinical test results were normal in 10 patients evaluated, except for both epinephrine- and exercise-induced ventricular arrhythmias in 1. EPS included bursts of ventricular pacing and programmed ventricular extrastimulation reproducing short-long sequences. Genetic screening involved direct sequencing of genes involved in long QT syndrome as well as RyR2. RESULTS: Six patients demonstrated a marked increase in QT interval only in the first beat after cessation of ventricular pacing and/or extrastimulation. All 6 patients were found to have a heterozygous missense mutation (M4109R) in RyR2. Two of them, presenting with aborted SCD, also had a second missense mutation (I406T- RyR2). Four family members without RyR2 mutations did not display prominent postpacing QT changes. CONCLUSION: M4109R- RyR2 is associated with a high incidence of SCD. The contribution of I406T to the clinical phenotype is unclear. In contrast to exercise testing, marked postpacing repolarization changes in a single beat accurately predicted carriers of M4109R- RyR2 in this family.

The mechanism of the negative chronotropic and dromotropic actions of adenosine 5'-triphosphate in the heart: an update.

Adenosine 5'-triphosphate (ATP) plays a critical role in intracellular metabolism and energetics. Extracellular ATP is rapidly degraded to adenosine by ectoenzymes. Both ATP and adenosine suppress cardiac pacemakers' automaticity and atrioventricular nodal conduction, albeit via the different mechanism of actions. This historical update summarizes the current knowledge regarding the negative chronotropic and dromotropic actions of ATP and discusses the clinical implications regarding the utility of ATP as a diagnostic and therapeutic agent in the management of neutrally mediated syncope and paroxysmal supra ventricular tachycardia.

Outcome after implantation of cardioverter defibrillator [corrected] in patients with Brugada syndrome: a multicenter Israeli study (ISRABRU).

BACKGROUND: Many electrophysiologists recommend implantable cardioverter defibrillators for patients with Brugada syndrome who are cardiac arrest survivors or presumed at high risk of sudden death (patients with syncope or a familial history of sudden death or those with inducible ventricular fibrillation at electrophysiologic study). OBJECTIVES: To assess the efficacy and complications of ICD therapy in patients with Brugada syndrome. METHODS: The indications, efficacy and complications of ICD therapy in all patients with Brugada syndrome who underwent ICD implantation in 12 Israeli centers between 1994 and 2007 were analyzed. RESULTS: There were 59 patients (53 males, 89.8%) with a mean age of 44.1 years. At diagnosis 42 patients (71.2%) were symptomatic while 17 (28.8%) were asymptomatic. The indications for ICD implantation were: a history of cardiac arrest (n = 11, 18.6%), syncope (n = 31, 52.5%), inducible VF in asymptomatic patients (n = 14, 23.7%), and a family history of sudden death (n = 3, 0.5%). The overall inducibility rates of VF were 89.2% and 93.3% among the symptomatic and asymptomatic patients, respectively (P = NS). During a follow-up of 4-160 (45 +/- 35) months, all patients (except one who died from cancer) are alive. Five patients (8.4%), all with a history of cardiac arrest, had appropriate ICD discharge. Conversely, none of the patients without prior cardiac arrest had appropriate device therapy during a 39 +/- 30 month follow-up. Complications were encountered in 19 patients (32%). Inappropriate shocks occurred in 16 (27.1%) due to lead failure/dislodgment (n = 5), T wave oversensing (n = 2), device failure (n = 1), sinus tachycardia (n = 4), and supraventricular tachycardia (n = 4). One patient suffered a pneumothorax and another a brachial plexus injury during the implant procedure. One patient suffered a late (2 months) perforation of the right ventricle by the implanted lead. Eleven patients (18.6%) required a reintervention either for infection (n = 1) or lead problems (n = 10). Eight patients (13.5%) required psychiatric assistance due to complications related to the ICD (mostly inappropriate shocks in 7 patients). CONCLUSIONS: In this Israeli population with Brugada syndrome treated with ICD, appropriate device therapy was limited to cardiac arrest survivors while none of the other patients including those with syncope and/or inducible VF suffered an arrhythmic event. The overall complication rate was high.

Provocation of sudden heart rate oscillation with adenosine exposes abnormal QT responses in patients with long QT syndrome: a bedside test for diagnosing long QT syndrome.

AIMS: As arrhythmias in the long QT syndrome (LQTS) are triggered by heart rate deceleration or acceleration, we speculated that the sudden bradycardia and subsequent tachycardia that follow adenosine injection would unravel QT changes of diagnostic value in patients with LQTS. METHODS AND RESULTS: Patients (18 LQTS and 20 controls) received intravenous adenosine during sinus rhythm. Adenosine was injected at incremental doses until atrioventricular block or sinus pauses lasting 3 s occurred. The QT duration and morphology were studied at baseline and at the time of maximal bradycardia and subsequent tachycardia. Despite similar degree of adenosine-induced bradycardia (longest R-R 1.7+/-0.7 vs. 2.2+/-1.3 s for LQTS and controls, P=NS), the QT interval of LQT patients increased by 15.8+/-13.1%, whereas the QT of controls increased by only 1.5+/-6.7% (P<0.001). Similarly, despite similar reflex tachycardia (shortest R-R 0.58+/-0.07 vs. 0.55+/-0.07 s for LQT patients and controls, P=NS), LQTS patients developed greater QT prolongation (QTc=569+/-53 vs. 458+/-58 ms for LQT patients and controls, P<0.001). The best discriminator was the QTc during maximal bradycardia. Notched T-waves were observed in 72% of LQT patients but in only 5% of controls during adenosine-induced bradycardia (P<0.001). CONCLUSION: By provoking transient bradycardia followed by sinus tachycardia, this adenosine challenge test triggers QT changes that appear to be useful in distinguishing patients with LQTS from healthy controls.

The "short-coupled" variant of right ventricular outflow ventricular tachycardia: a not-so-benign form of benign ventricular tachycardia?

Idiopathic ventricular tachycardia (VT) originating from the right ventricular outflow tract (RVOT-VT) and idiopathic RVOT-extrasystoles are generally considered benign arrhythmias. We described three cases who originally presented with typical "benign looking" RVOT-extrasystoles or RVOT-VT but developed malignant polymorphic VT during follow-up. The unusual aspect of their RVOT-extrasystoles was their coupling interval, which appears to be intermediate between the ultra-short coupling interval of idiopathic VF and the long coupling interval seen in the truly benign RVOT-VT.

Incidence of dual AV node physiology following termination of AV nodal reentrant tachycardia by adenosine-5'-triphosphate: a comparison with drug administration in sinus rhythm.

Administration of adenosine triphosphate (ATP) in sinus rhythm identifies dual atrioventricular node physiology (DAVNP) in 75% of patients with inducible slow/fast AV nodal reentrant tachycardia (AVNRT). The incidence of DAVNP following termination of AVNRT with ATP is unknown. Incremental doses of ATP (10-60 mg) were administered, first in sinus rhythm and then during tachycardia induced at electrophysiologic study, to 84 patients with inducible AVNRT and to 18 control patients with inducible AV reentrant tachycardia (AVRT) and no electrophysiologic evidence of DAVNP. Study end-points were the occurrence of DAVNP or > or = 2nd degree AV block following administration of ATP in sinus rhythm and tachycardia termination following administration of ATP during tachycardia. Of the 82 patients with AVNRT who completed the study, 62 (75.6%) exhibited DAVNP following administration of 17.1 +/- 9.4 mg ATP in sinus rhythm, while 30 (36.5%) exhibited DAVNP at the termination of AVNRT following administration of 10.6 +/- 2.4 mg ATP. The occurrence of DAVNP following the administration of 10 mg ATP in sinus rhythm.was a good predictor (62%) of its occurrence after termination of AVNRT with ATP. The dose of ATP had a strong correlation between the presence of DAVNP following AVNRT termination and the ATP doses needed for tachycardia termination. Of the 18 control patients, none had DAVNP at ATP test during sinus rhythm but 1 (5.5%) showed slight (60 msec) PR jump after termination of AVRT with ATP. In conclusion, DAVNP is present in a relatively high proportion (36.5%) of patients following termination of AVNRT with ATP but is much less frequent (5.5%) in control patients. Thus, findings at termination of tachycardia by ATP may be useful in the noninvasive diagnosis of the mechanism of a paroxysmal supraventricular tachycardia.