[Diagnostic use of adenosine triphosphate in cardiac arrhythmias]. / Utilisation diagnostique de l'adénosine triphosphate dans les arythmies cardiaques.

Adenosine triphosphate (ATP) has been used for more than 50 years as a major medication in our therapeutic arsenal for the termination of supraventricular tachycardia crises for which the mechanism is re-entry implicating the atrioventricular node. In the present article other applications of ATP as a diagnostic agent for several cardiac arrhythmias are described: differential diagnosis of narrow or wide QRS tachycardia, diagnosis of a latent accessory pathway (intermittent or hidden), diagnosis of intranodal duality, and non-invasive evaluation of the results of the ablation of the slow pathway, and finally non-invasive diagnosis of the tachycardia mechanism in patients with palpitations or tachycardia with an obscure mechanism.

Pause-dependent torsade de pointes following acute myocardial infarction: a variant of the acquired long QT syndrome.

OBJECTIVES: We report on a previously unrecognized form of the long QT syndrome (QT interval prolongation and pause-dependent polymorphic ventricular tachycardia [VT]) entirely related to myocardial infarction (MI). BACKGROUND: Polymorphic VT in the setting of acute MI generally occurs during the hyperacute phase, is related to ischemia, and is not associated with QT prolongation. Although QT prolongation after MI is well described, typical pause-dependent polymorphic VT (torsade de pointes) secondary to uncomplicated MI was previously unknown. METHODS: Of 434 consecutive admissions for acute MI, 8 patients had progressive QT prolongation that led to typical torsade de pointes. None of these patients had active ischemia or other known causes of QT prolongation. These patients were compared with 100 consecutive patients with uncomplicated MI who served as controls. RESULTS: The incidence of torsade de pointes following MI was 1.8% (95% confidence interval 0.8% to 3.6%). The QTc intervals of patients and controls were similar on admission. The QTc lengthened by day 2 in both groups, but more so in patients with torsade de pointes (from 470 +/- 46 to 492 +/- 57 ms [p < 0.05] and from 445 +/- 58 to 558 +/- 84 ms, respectively [p < 0.01]). Maximal QT prolongation and torsade de pointes occurred 3 to 11 days after infarction. Therapy included defibrillation, magnesium, lidocaine and beta-blockers. Three patients required rapid cardiac pacing. The long-term course was uneventful. CONCLUSIONS: Infarct-related torsade de pointes is uncommon but potentially lethal. An acquired long QT syndrome should be considered in patients recovering from MI who experience polymorphic VT as specific therapeutic measures are mandatory.

The adenosine triphosphate test: a bedside diagnostic tool for identifying the mechanism of supraventricular tachycardia in patients with palpitations.

OBJECTIVES: This study assesses the value of the "ATP test" (injection of adenosine triphosphate [ATP] during sinus rhythm) for identifying patients with palpitations of unclear etiology who actually have atrioventricular (AV) nodal re-entry tachycardia (AVNRT) or AV re-entry tachycardia (AVRT). BACKGROUND: Because AVNRT and AVRT can be cured with radiofrequency ablation, documentation of spontaneous AVNRT or AVRT usually prompts referral for electrophysiologic (EP) evaluation. However, these paroxysmal arrhythmias may elude clinical diagnosis. We recently showed that administration of ATP during sinus rhythm often reveals dual AV node physiology or a concealed accessory pathway (AP) in patients with documented AVNRT or AVRT. Thus, we postulated that the ATP test could identify patients with palpitations who actually have AVNRT or AVRT and would therefore benefit from EP evaluation. METHODS: One hundred forty-six patients (54 with "palpitations without documented arrhythmias" and 92 with "documentation of arrhythmias of unclear mechanism") underwent a noninvasive ATP test. ATP was injected during sinus rhythm using 10 mg increments. The ATP test was considered positive when prospectively defined signs of dual AV node physiology or concealed AP were disclosed in the electrocardiogram. These findings were correlated with the results of EP evaluation. RESULTS: A positive ATP test predicted induction of AVNRT or AVRT with a positive predictive value of 93% (sensitivity 71%) but a negative predictive value of 37% (specificity 76%). CONCLUSIONS: A bedside ATP test identifies patients with palpitations who are likely to have AVNRT or AVRT (and who are therefore likely to benefit from EP evaluation) with a high positive predictive value.

Genetic analysis of Brugada syndrome in Israel: two novel mutations and possible genetic heterogeneity.

Idiopathic ventricular fibrillation in patients with an electrocardiogram (ECG) pattern of right bundle branch block and ST-segment elevation in leads V1 to V3 (now frequently called Brugada syndrome) is associated with a high incidence of syncopal episodes or sudden death. The disease is inherited as an autosomal dominant trait. Mutations in SCN5A, a cardiac sodium channel gene, have been recently associated with Brugada syndrome. We have analyzed 7 patients from Israel affected with Brugada syndrome. The families of these patients are characterized by a small number of symptomatic members. Sequencing analysis of SCN5A revealed two novel mutations, G35S and R104Q, in two Brugada patients, and a possible R34C polymorphism in two unrelated controls. No mutations were detected in 5 other patients, suggesting genetic heterogeneity. Low penetrance is probably the cause for the small number of symptomatic members in the two families positive for the SCN5A mutations.

Adenosine-5'-triphosphate test for the noninvasive diagnosis of concealed accessory pathway.

OBJECTIVES: This study assessed the use of adenosine triphosphate (ATP) in the noninvasive diagnosis of concealed accessory pathway (AP) and dual atrioventricular (AV) node physiology in patients with inducible AV reentrant tachycardia (AVRT). BACKGROUND: Administration of ATP during sinus rhythm identifies dual AV node physiology in 76% of patients with inducible sustained slow/fast AV nodal reentry tachycardia (AVNRT). METHODS: Incremental doses of ATP were intravenously administered during sinus rhythm to 34 patients with inducible sustained AVRT involving a concealed AP and to 27 control patients without AP or dual AV node physiology. One study group patient could not complete the study and was excluded from analysis. RESULTS: The AV reentrant echo beats (AVRE), or AVRT, suggestive of the presence of concealed AP, were observed after ATP administration in 24 (73%) study patients and in none of the control group. Electrocardiographic signs suggestive of dual AV node physiology were observed after ATP administration in 7 (21%) study patients and in none of the control group. Most instances of AVRE/AVRT were preceded by a slight increase (<50 ms) in PR interval. In 8 of 9 patients tested, neither AVRE nor AVRT was no longer observed following ATP administration after successful radiofrequency ablation of the AP. In the remaining patient, a different AVRE due to the presence of an additional AP was observed. CONCLUSIONS: Administration of ATP during sinus rhythm may be a useful bedside test for identifying patients with concealed AP who are prone to AVRT and those with associated dual AV node pathways.

Prevalence of the Brugada sign in idiopathic ventricular fibrillation and healthy controls.

OBJECTIVE: To determine the prevalence of the Brugada sign (right bundle branch block with ST elevation in V1-V3) in idiopathic ventricular fibrillation and in an age matched healthy population. DESIGN: ECGs from 39 consecutive patients with idiopathic ventricular fibrillation and 592 healthy controls were reviewed. They were classified as definite, questionable, and no Brugada sign (according to predetermined criteria) by four investigators blinded to the subjects' status. RESULTS: Eight patients (21%) with idiopathic ventricular fibrillation but none of the 592 controls had a definite Brugada sign (p < 0.005). Thus the estimated 95% confidence limits for the prevalence of a definite Brugada sign among healthy controls was less than 0.5%. A questionable Brugada sign was seen in two patients with idiopathic ventricular fibrillation (5%) but also in five controls (1%) (p < 0.05). Normal ECGs were found following resuscitation and during long term follow up in 31 patients with idiopathic ventricular fibrillation (79%). Patients with idiopathic ventricular fibrillation and a normal ECG and those with the Brugada syndrome were of similar age and had similar spontaneous and inducible arrhythmias. However, the two groups differed in terms of sex, family history, and the incidence of sleep related ventricular fibrillation. CONCLUSIONS: A definite Brugada sign is a specific marker of arrhythmic risk. However, less than obvious ECG abnormalities have little diagnostic value, as a "questionable" Brugada sign was observed in 1% of healthy controls. In this series of consecutive patients with idiopathic ventricular fibrillation, most had normal ECGs.

Arrhythmias in the congenital long QT syndrome: how often is torsade de pointes pause dependent?

OBJECTIVE: To determine the frequency and predictors of pause dependent torsade de pointes among patients with the congenital long QT syndrome and spontaneous ventricular tachyarrhythmias. DESIGN: The literature on the "congenital long QT" was reviewed. Articles with illustrations demonstrating the onset of spontaneous polymorphic ventricular arrhythmias in the absence of arrhythmogenic drugs were included. RESULTS: Illustrations of 62 spontaneous episodes of torsade de pointes among patients with congenital long QT syndrome were found in the literature. The majority (74%) of documented arrhythmias were "pause dependent"; 82% of these pauses were longer than the basic cycle length by > 100 ms. Age and sex correlated with the mode of arrhythmia initiation. Arrhythmias in infants (

Simplified "ATP test" for noninvasive diagnosis of dual AV nodal physiology and assessment of results of slow pathway ablation in patients with AV nodal reentrant tachycardia.

INTRODUCTION: We recently reported that administration of adenosine triphosphate (ATP) during sinus rhythm identifies dual AV nodal physiology (DAVNP) in 76% of patients with inducible sustained AV nodal reentrant tachycardia (AVNRT) at electrophysiologic (EP) study. In that report, however, the ATP test was considered positive for DAVNP only when the results were reproducible at a given dose of ATP. The aim of the present study was to assess the value of a simplified ATP test for noninvasive diagnosis of DAVNP and abolition or modification of the slow pathway (SP) after radiofrequency ablation (RFA) in patients with inducible sustained AVNRT. METHODS AND RESULTS: The value of a single dose of ATP was studied in 105 patients with inducible sustained AVNRT and in 31 control patients before placement of EP catheters in the cardiac chambers. ATP (10 to 60 mg, in 10-mg increments) was injected during sinus rhythm until ECG signs of DAVNP (> or = 50 msec increase or decrease in PR interval in two consecutive beats, or occurrence of > or = 1 AV nodal echo beat) or > or = second-degree AV block was observed. DAVNP was observed in only 1 (3.2%) control patient. The test could be completed in 96 study patients. DAVNP was found by ATP test in 72 (75%) patients, whereas it was diagnosed by EP criteria in 82 (85%) patients. DAVNP by ATP test disappeared in 27 (96%) of 28 patients who underwent SP abolition and in 18 (60%) of 30 patients who underwent SP modification. In the 12 patients with persistent DAVNP determined by ATP test after SP modification, the number of beats conducted over the SP was significantly reduced (from 6.3+/-3.3 to 2.5+/-2.2 beats; P = 0.002). CONCLUSION: A single administration of ATP during sinus rhythm (at a given dose) enables noninvasive diagnosis of DAVNP in a high percentage of patients with inducible AVNRT and reliably confirms the results of RFA of the SP.

Long-term follow-up of patients with long-QT syndrome treated with beta-blockers and continuous pacing.

BACKGROUND: The long-QT syndrome is associated with sudden cardiac death. Combination of beta-blocker and pacing therapy has been proposed for treatment of drug-resistant patients. The purpose of this study was to summarize our long-term experience with combined therapy in patients with long-QT syndrome. METHODS AND RESULTS: A total of 37 patients with idiopathic long-QT syndrome were treated with combined therapy consisting of continuous cardiac pacing and maximally tolerated beta-blocker therapy and followed up for 6.3+/-4. 6 years (mean+/-SD). The group consisted of 32 female and 5 male patients with a mean age of 31.6 years. The mean paced rate was 82+/-7 bpm (range, 60 to 100 bpm). On follow-up, recurrent symptoms caused by pacemaker malfunction were documented in 3 patients. Four patients died during the follow-up period: 2 adolescents stopped beta-blocker therapy, 1 patient died suddenly while treated with combined therapy, and 1 patient died of unrelated causes. In addition, 3 patients had resuscitated cardiac arrest while on combined therapy, and 1 patient had repeated, appropriate implantable cardioverter-defibrillator discharges on follow-up. CONCLUSIONS: Because 28 of 37 patients remain without symptoms with beta-blocker therapy and continuous pacing, combined therapy appears to provide reasonable, long-term control for this high-risk group. However, the incidence of sudden death and aborted sudden death (24% in all patients and 17% in compliant patients) strongly suggests the use of a "back-up" defibrillator, particularly in noncompliant adolescent patients. Implantable cardioverter-defibrillator therapy, however, may be associated with recurrent shocks in susceptible patients.

Effects of electrophysiologic-guided therapy with Class IA antiarrhythmic drugs on the long-term outcome of patients with idiopathic ventricular fibrillation with or without the Brugada syndrome.

INTRODUCTION: Implantation of a implantable cardioverter defibrillator (ICD) is viewed universally as the "gold standard" therapy for patients with idiopathic ventricular fibrillation (VF). We sought to study the long-term value of electrophysiologic (EP)-guided therapy with Class IA antiarrhythmic drugs in patients with idiopathic VF with or without the Brugada syndrome. METHODS AND RESULTS: We performed EP studies in 34 consecutive patients who had idiopathic VF with (n = 5) or without (n = 29) the Brugada syndrome. All patients with inducible sustained polymorphic ventricular tachycardia (SPVT) or VF underwent repeated EP evaluation after oral administration of a Class IA antiarrhythmic drug (mainly quinidine). Patients rendered noninducible received this therapy on a long-term basis. SPVT/VF were induced in 27 (79.4%) patients at baseline studies. Class IA drugs effectively prevented induction of SPVT/VF in 26 (96%) patients. Of the 23 patients treated with these medications, no patient died or had a sustained ventricular arrhythmia during a mean follow-up period of 9.1 +/- 5.6 years (7 to 20 years in 15 patients). Two deaths occurred in patients without inducible SPVT/VF at baseline studies who had been treated empirically. CONCLUSION: Our results suggest that EP-guided therapy with Class IA agents is a reasonable, safe, and effective approach for the long-term management of patients with idiopathic VF. A randomized prospective study of EP-guided Class IA therapy in patients with ICDs seems warranted.

Atypical AV nodal reentry with bystander accessory pathway: an unusual mechanism of preexcited tachycardia.

We present an unusual mechanism of preexcited tachycardia--atypical AV nodal reentry with bystander AP. It can be differentiated from other preexcited tachycardias by its variable degree of preexcitation (either spontaneous or in response to atrial pacing), higher degree of preexcitation with pacing near the origin of the AP than during tachycardia, inability to preexcite the tachycardia by either late atrial or ventricular premature beats, the presence of nonpreexcited atypical AV nodal reentry tachycardia following successful AP ablation, and by exclusion of atrial tachycardia.

Catheter-induced mechanical trauma to accessory pathways during radiofrequency ablation: incidence, predictors and clinical implications.

OBJECTIVES: To evaluate the incidence, predictors and clinical implications of nonintentionally catheter-induced mechanical trauma to accessory pathways during radiofrequency ablation procedures. BACKGROUND: Data on the incidence and significance of catheter-induced trauma to accessory pathways are scarce. METHODS: Consecutive patients (n = 381) undergoing radiofrequency ablation of accessory pathways at two different institutions were closely monitored for appearance of mechanical block of accessory pathways during catheter manipulation. RESULTS: Mechanical trauma to accessory pathways was observed in 37 (9.7%) patients. According to a multivariate analysis, the only independent variable associated with this phenomenon was the anatomical pathway location (p = 0.0001). The incidence of trauma of either right anteroseptal (38.5%) or right atriofascicular pathways (33.3%) was significantly greater than that of pathways (< or =10%) at all remaining locations (p < 0.0001). The duration of conduction block observed ranged from < or =1 min to >30 min in 19% and 35% of patients, respectively. "Immediate" application of radiofrequency pulses at sites of mechanical block (<1 min after occurrence) was associated with a 78% long-term success rate at follow-up. This contrasted with a 25% long-term success rate in patients in whom pulses were delivered 30 min after occurrence of block ("delayed pulses"). Finally, in 24% of patients persistent trauma-induced conduction block led to discontinuation of the ablation procedure. CONCLUSIONS: Trauma to accessory pathways is more common than previously recognized and frequently results in prolongation or discontinuation of the ablation procedure and in lower success rates. The only independent predictor of catheter-trauma to accessory pathways is the pathway location.

Polymorphic ventricular tachyarrhythmias in the absence of organic heart disease: classification, differential diagnosis, and implications for therapy.

Different polymorphic ventricular tachyarrhythmias may cause syncope or cardiac arrest in patients with no heart disease: (1) Catecholamine-sensitive polymorphic ventricular tachycardia (VT) presents during childhood: the hallmark is the reproducible provocation of atrial and polymorphic ventricular arrhythmias during exercise, despite a normal QT. Beta-blockers are the treatment of choice. (2) In the long QT syndromes (LQTS), malfunction of ion channels leads to prolonged ventricular repolarization, early afterdepolarizations, and triggered ventricular arrhythmias. Therapeutic options include: beta-blockers, genotype-specific therapy, cardiac sympathetic denervation, and implantation of pacemakers or defibrillators. (3) The "short-coupled variant of torsade de pointes" is a malignant disease that shares several characteristics with idiopathic ventricular fibrillation. Although verapamil is frequently recommended, mortality rates remain high. (4) Idiopathic ventricular fibrillation (VF) with normal electrocardiogram (ECG) strikes young adults of both genders. In contrast to other polymorphic tachyarrhythmias, idiopathic VF is not generally related to stress. Also, familial involvement is rare. Therapeutic options include implantation of defibrillators and therapy with class 1A drugs. (5) The "Brugada syndrome" and the "syndrome of nocturnal sudden death" strike males almost exclusively. Right bundle branch block (RBBB) with ST elevation in the right precordial leads-the "Brugada sign"--is seen in the ECG of both patient populations. Implantation of defibrillators is recommended.

Noninvasive diagnosis of dual AV node physiology in patients with AV nodal reentrant tachycardia by administration of adenosine-5'-triphosphate during sinus rhythm.

BACKGROUND: Atrioventricular nodal reentry tachycardia (AVNRT) represents the most commonly encountered type of regular paroxysmal supraventricular tachycardia. This study determined whether administration of adenosine-5'-triphosphate (ATP) during sinus rhythm may be useful in the noninvasive diagnosis of dual AV nodal pathways. METHODS AND RESULTS: During electrophysiological study, we intravenously administered incremental doses of ATP (from 10 to 50 mg) during sinus rhythm to patients with spontaneous and inducible sustained AVNRT (study group, n=42) and to patients with no evidence of dual AV nodal physiology or inducible AVNRT (control group, n=21). Signs suggestive of dual AV node physiology after ATP administration during sinus rhythm ("jump" of AH > or =50 ms between 2 consecutive beats, > or =1 AV nodal echo beat, or initiation of AVNRT) were observed in 32 (76%) of 42 study patients but in only 1 (5%) of the 21 control patients (P<0.001). Similar results were observed when only surface lead recordings (without intracardiac recordings) were evaluated. Signs suggestive of dual AV node physiology by the ATP test were observed in 29 (80.5%) of 36 patients who had electrophysiological demonstration of dual AV node physiology and in 3 (50%) of 6 patients without AV nodal duality (P=NS). Signs suggestive of dual physiology according to the ATP test disappeared in 11 (92%) of the 12 patients who underwent successful slow AV nodal ablation but persisted in 8 (62%) of 13 patients who underwent AV nodal modification. CONCLUSIONS: Administration of ATP during sinus rhythm may be a useful bedside test for identifying patients with dual AV nodal pathways who are prone to AVNRT. This simple test should be considered as a screening test for patients with symptoms suggestive of paroxysmal supraventricular tachycardia but no documented arrhythmias or for patients with documented narrow complex tachycardia of unclear mechanism.