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.

Autonomic dysfunction in experimental autoimmune neuritis: heart rate.

Autonomic nervous system (ANS) dysfunction occurs in more than half of Guillain--Barré syndrome (GBS) patients and is an important cause of death in the disease. In this study we examined heart rate (HR) changes in an animal model of GBS, experimental autoimmune neuritis (EAN), induced by immunization with myelin extracted from bovine spinal roots. The animals developed progressive motor weakness accompanied by significant weight loss and hypothermia. HR was measured in 33 EAN rats at rest (rHR) and followings stressful stimulation (sHR). Average pre-immunization rHR was 341+/-28 beats per minute (b.p.m.) and sHR was 486+/-21 bpm. Although the mean rHR in rats with EAN was not significantly different compared to that at baseline, there was a significant increase of variation of rHR with six rats demonstrating bradycardia (<280 b.p.m.) and 10 tachycardia (>400 b.p.m.) (P<0.01, F-test). sHR in EAN rats was significantly lower (P<0.01), suggesting sympathetic system impairment. These findings may serve as a basis for testing treatments of ANS dysfunction in EAN.

Prevention of ventricular arrhythmias in the congenital long QT syndrome.

Life-long therapy is necessary for patients with symptomatic long QT syndrome to prevent arrhythmic death. The merits and limitations of the different therapeutic modalities are discussed. beta-blockers remain the mainstay of therapy, but this medication may not be sufficient for cardiac arrest survivors and for those with the LQT3 genotype. "Genotype-specific" therapy, like potassium-channel openers for patients with inadequate potassium outflow (LQT1 and LQT2 genotypes) or sodium-channel blockers for patients with excessive sodium inflow (LQT3), significantly shortens the QT interval, but the effects of these drugs on arrhythmia prevention is less well established. Cardiac pacemakers may be especially beneficial for patients with LQT2 or LQT3 and for those with pause-dependent torsade de pointes. More important is to recognize that device programming for preventing tachyarrhythmias in patients with long QT differs from the standard pacemaker programming. Finally, implantable defibrillators with dual-chamber pacing capability are indicated for patients at high risk for arrhythmic death, including all cardiac arrest survivors.

Rate smoothing with cardiac pacing for preventing torsade de pointes.

Cardiac pacing remains one of the most effective means for preventing torsade de pointes in patients with long QT syndrome (LQTS). However, fatal arrhythmias may occur despite combined therapy with beta blockers and pacing, and it is possible that failure of cardiac pacing for preventing arrhythmias in the long run is related (at least in part) to suboptimal pacemaker programming. Preventing sudden pauses may be especially important for preventing arrhythmias in the LQTS because such pauses are highly proarrhythmic in this patient population. Unfortunately, properly functioning pacemakers cannot be expected to prevent postextrasystolic pauses. The use of a pause-prevention pacing algorithm-rate smoothing-for preventing pause-dependent torsade de pointes is described in 12 patients with cardiac arrest or syncope due to congenital LQTS who were followed for 21 +/- 11 months.

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.

Cardiac pacing in the long QT syndrome: review of available data and practical recommendations.

A review of published data on cardiac pacing in the long QT syndrome (LQTS) is presented, in the hope that optimization of patient selection and pacemaker programming will prevent arrhythmic death. LQT3 patients may derive particular benefit from pacing because the dispersion of repolarization worsens steeply during bradycardia in this genotype. However, concluding that other genotypes will not benefit from pacing is premature. Pacing may be especially beneficial for patients with "pause-dependent" arrhythmias. Programming should include a sufficiently fast lower rate limit. Features that allow heart rate slowing beyond the lower rate limit or that may trigger pauses must be programmed "off" because pauses are proarrhythmic in this population. Pause-prevention pacing algorithms may be beneficial.

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 QT syndromes and torsade de pointes.

In the long QT syndromes (LQTS), malfunction of ion channels impairs ventricular repolarisation and triggers a characteristic ventricular tachyarrhythmia: torsade de pointes. Symptoms in the LQTS (syncope or cardiac arrest) are caused by this arrhythmia. In congenital LQTS, mutations in the genes encoding for ion channels cause this channel malfunction. Six genotypes (LQT1 to LQT6) have been identified, and attempts are being made to correlate different mutations with clinical signs and specific therapy. In acquired LQTS, channel malfunction is caused by metabolic abnormalities or drugs. The list of drugs that may impair ion-channel function expands continuously. Moreover, attributes that increase the risk for drug-induced torsade (eg, female sex, recent heart-rate slowing, or hypokalaemia) and electrocardiographic "warning signs" are recognised. Recent data suggest that patients with an acquired LQTS have some underlying predisposition to proarrhythmia. Mutations causing "silent" forms of congenital LQTS, in which the patient remains free of arrhythmias until exposed to drugs that further impair repolarisation, are now recognised.

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.

Circadian variation of symptomatic paroxysmal atrial fibrillation. Data from almost 10 000 episodes.

AIMS: To determine the circadian rhythm of paroxysmal atrial fibrillation in a very large outpatient population. METHODS AND RESULTS: We reviewed all emergency telephone calls received in Shahal (a medical service covering 44 000 subscribers), from 1987 to 1997. Patients were included if new-onset atrial fibrillation was recorded. During this study period, 9989 episodes of paroxysmal atrial fibrillation were recorded. The time of onset was not uniformly distributed throughout the 24 h period. Instead, the distribution of arrhythmic episodes showed a double peak, with a significant increase in the number of episodes in the morning and a second rise in the evening (P<0.001). A non-uniform weekly distribution of events was also noted, with substantially fewer episodes on Saturdays (P<0.001). Finally, more arrhythmias occurred during the last months of each year (P<0.001). CONCLUSIONS: The onset of paroxysmal atrial fibrillation does not occur randomly. The large patient population in the present study suggests that the circadian rhythm of paroxysmal atrial fibrillation is similar to that described for other cardiovascular diseases, with clustering of events in the morning and (to a lesser degree) late in the evening. Weekly and yearly circadian patterns are also prominent.