Effects of intravenous adenosine on verapamil-sensitive “idiopathic” ventricular tachycardia

Ventricular arrhythmias and sudden cardiac death

29 - Ablation of Idiopathic Left and Right Ventricular and Fascicular Tachycardias

Idiopathic left ventricular tachycardia (VT) has been classified into three subgroups according to mechanism: verapamil-sensitive, adenosine-sensitive, and propranolol-sensitive types. VT can be categorized also into left fascicular VT and left outflow tract VT. Although the mechanism of fascicular VT is verapamil-sensitive reentry, the mechanism of left outflow tract VT is not homogeneous. Fascicular VT can be classified into three subtypes: (1) left posterior fascicular VT with a right bundle branch block (RBBB) and superior axis configuration (common form); (2) left anterior fascicular VT with RBBB and right-axis deviation configuration (uncommon form); and (3) upper septal fascicular VT with a narrow QRS and normal axis configuration (rare form). Posterior and anterior fascicular VT can be successfully ablated at the mid-septum guided by a diastolic Purkinje potential or at the VT exit site guided by a fused presystolic Purkinje potential. Upper septal fascicular VT also can be ablated at the site indicated by a diastolic Purkinje potential. The mechanism of left ventricular outflow tract VT is most likely adenosine-sensitive triggered activity. This VT can be classified into three subtypes according to the location where catheter ablation is successful, i.e., (1) endocardial origin; (2) coronary cusp origin; and (3) epicardial origin. The R-wave duration and R/S-wave amplitude in V1/V2 can be used to differentiate coronary cusp VT from other types of outflow tract VT. Recognition of the characteristics of the various forms of this group of arrhythmias should facilitate appropriate diagnosis and therapy.

Muscle sympathetic nerve traffic during spontaneous- versus adenosine-mediated termination of idiopathic right ventricular outflow tract tachycardia

It is generally accepted that the diagnosis of an epicardial origin of ventricular tachycardia (VT) can be made indirectly by observing VT termination during ablation on the epicardial surface of the heart. There is a caveat, however, which is that termination of VT during radiofrequency current application on the epicardial surface could be due to extension of the lesion beyond the epicardium. Therefore, successful ablation of VT using an epicardial approach does not necessarily prove the reentrant circuit is located superficially. We present a case of a 44-year-old man with VT storm who demonstrated successful termination of VT with radiofrequency current application on the epicardial surface of the heart. This site corresponded to a site where pacing during VT resulted in termination of VT without global capture. Isolated mid-diastolic potentials were only seen at this site as well. We hypothesize that the finding of termination of VT by pacing without global capture supports the argument that the site of pacing is a critical part of the VT circuit.

Right ventricular outflow tract (RVOT) tachycardia is the most common form of idiopathic ventricular tachycardia (VT). Phenotypically, RVOT tachycardia segregates into two predominant forms, one characterized by repetitive monomorphic nonsustained VT and the other by paroxysmal exercise induced sustained VT. There is an increasing body of evidence to support the concept that both forms of tachycardia reflect disparate clinical manifestations of an identical cellular mechanism (i.e., cAMP-mediated triggered activity), which is identified clinically by the tachycardia's sensitivity to adenosine. The clinical characteristics, natural history, and approaches to therapy of RVOT tachycardia are delineated herein.

Amiodarone Is Poorly Effective for the Acute Termination of Ventricular Tachycardia

A rapid wide complex tachycardia

27 - Idiopathic focal ventricular tachycardia

The ECG in Fig. 1 shows a QRS tachycardia with a QRS duration of 146 ms and a frequency of 160 beats/min. There is a left axis deviation and a complete right bundle branch block. It is important to make a differentiation between ventricular tachycardia (VT) and supraventricular tachycardia (SVT). Signs suggestive of both a ventricular and supraventricular origin are present in our patient. The tachycardia was terminated by adenosine. This is (usually) suggestive of a supraventricular origin. So differential diagnostic paroxysmal SVT conducted with aberrancy is a possibility because of its relatively narrow QRS. The presence of ventriculoatrial dissociation in the electrocardiogram makes the diagnosis of VT stronger. If assuming a ventricular origin, VT originating in or near the Purkinje system (fascicular VT or idiopathic left ventricular VT) is likely. Fig. 1 Twelve-lead ECG during and after conversion to sinus rhythm In 1979, Zipes et al. were the first to identify the electrophysiological characteristics of an idiopathic VT. In 1981 Belhassen et al. described the use of verapamil in this VT, which is refractory to conventional treatment [1]. Therefore, this VT is commonly referred to as Belhassen, verapamil-sensitive or fascicular VT. It is characterised by a right bundle branch block pattern and left axis deviation (left posterior fascicle). A right axis deviation is less frequently noted. The prevalence is unknown but patients are typically young and healthy when their first episode occurs. It is more common in males than females. The mechanism of the tachycardia is postulated to be triggered activity or reentry involving the left-sided Purkinje system and abnormal Purkinje or myocardial tissue [2]. The termination of fascicular VT usually requires intravenous antiarrhythmic medication. In patients with frequent or symptomatic fascicular VT long-term medication may be required. Patients with recurrent refractory episodes of VT may be referred for radiofrequency ablation. The prognosis of fascicular VT is good, in just a few cases it can result in a tachycardia-induced cardiomyopathy. Syncope and sudden death are extremely rare [3].

The safety and efficacy of adenosine in treating atrioventricular (AV) nodal reentrant and AV reciprocating tachycardias are well established [1]. Adenosine depresses the upstroke of the action potential of AV nodal cells ("N" cells). Although the ionic mechanism for this depression is unknown, it is the most likely cause of adenosine-induced impairment of AV nodal conduction [2]. The short half-life of adenosine (<6-10 s) primarily accounts for its safety [3,4]. Because of both its safety and efficacy, adenosine has become the drug of choice in the treatment of paroxysmal supraventricular tachycardia. Less well appreciated is a form of ventricular tachycardia (VT) which, because of its mechanism of initiation, is sensitive to adenosine. It has been most frequently observed in patients with structurally normal hearts and in whom the VT was exercise induced [5]. The proposed mechanism of initiation involves after-depolarizations triggered by the preceding action potential (triggered activity) [6]. Catecholamines have been demonstrated experimentally to induce triggered activity, and the initiation of this form of VT is believed to be caused by intracellular calcium (Cai2+) overload mediated by elevation of intracellular cyclic adenosine monophosphate (cAMP) [7]. Therefore, catecholamines appear to play a pivotal role in the initiation of this type of VT. We describe a patient undergoing hypothermic cardiopulmonary bypass for coronary artery bypass grafting (CABG) who was observed to be hyperdynamic during rewarming and who developed a wide-complex tachycardia sensitive to adenosine. Case Report A 67-yr-old man with a history of progressive shortness of breath and dyspnea on exertion was admitted to the hospital for CABG. He was taking aspirin 325 mg daily and diltiazem 90 mg twice a day. Past medical history was unremarkable except for degenerative joint disease and reflux esophagitis. Left ventricular and coronary angiography revealed mild to moderate hypokinesis in the posterobasal and posterolateral segments, respectively, left ventricular end diastolic pressure 14 to 29 mm Hg, and an ejection fraction of 0.68. The major arteriographic findings were 80% obstruction of the proximal left anterior descending coronary artery, 70% obstruction of the first diagonal, 100% occlusion of the proximal circumflex, and 90% obstruction of the proximal right coronary artery. During exercise radionucleotide angiography, which was positive for ischemia, the electrocardiogram (ECG) showed >2 mm ST segment depression, "T wave inversion, supraventricular tachycardia, and complex ventricular ectopy," with the heart rate reaching 150 bpm. Arterial blood pressure increased from 132/70 mm Hg at rest to 220/100 mm Hg at peak exercise. The test was stopped at 7.0 min because of dyspnea. The patient was brought to the operating room, and anesthesia was induced with 250 micro gram sufentanil and 4.5 mg midazolam intravenously (IV). Endotracheal intubation was facilitated by administration of 6 mg of pancuronium bromide and 6 mg of vecuronium IV. Monitoring included five-lead electrocardiography, systemic blood pressure with a left radial arterial catheter, pulse oximetry, nasopharyngeal temperature, and capnography. Additionally, a pulmonary artery catheter was placed via the right internal jugular vein for purposes of pulmonary artery and pulmonary artery occlusion pressure monitoring and for thermodilution measurement of cardiac output. Anesthesia was maintained with sufentanil and midazolam, nitrous oxide, oxygen, and air. Supplemental relaxation was accomplished with 2 mg incremental pancuronium bromide. The pre-cardiopulmonary bypass (CPB) course was uneventful. A total dose of 1500 micro gram sufentanil (15 micro gram/kg) was administered prior to CPB. Saphenous vein grafts were inserted into the diagonal, circumflex, and posterior descending coronary arteries, and the left internal mammary artery was anastomosed to the left anterior descending coronary artery. Bypass and aortic cross-clamp times were 113 and 57 min, respectively. Ten minutes after removal of the aortic cross-clamp, a wide-complex tachycardia occurred Figure 1. The tachycardia persisted despite three successive attempts at electrical defibrillation (20 J, 20 J, 30 J) and 100 mg IV lidocaine. The PaO2 was 315 mm Hg, PaCO2 48 mm Hg, pHa 7.35, bicarbonate 27 mEq/L, base deficit +2 mEq/L, and potassium 4.5 mEq/L. Core temperature was 37 degrees C. There was no ECG evidence of an acute ischemic event or of difficulty with internal mammary artery or vein graft function.Figure 1: Wide-QRS complex tachycardia with a cycle length of 375 ms (160 bpm). The upper tracing is from precordial lead 5 and the lower, lead 2. Atrioventricular dissociation is present, evident by the P wave preceding the third QRS complex, confirming this to be ventricular tachycardia.Given the patient's prior history of a hyperdynamic response and complex ventricular ectopy with exercise, in addition to the observed hyperdynamic state during rewarming after CPB, a presumptive diagnosis of catecholamine-mediated VT was made. A 6-mg dose of adenosine was injected into the oxygenator reservoir without effect. This was followed in 2 min by a 12-mg bolus, with resulting termination of the tachycardia within 20 s Figure 2. The patient was removed from CPB without difficulty. Infusions of sodium nitroprusside (0.5 micro gram centered dot kg-1 centered dot min-1) and dopamine (2.0 micro gram centered dot kg-1 centered dot min-1) were started. the patient received a total of 3.0 mg of propranolol for management of three- to seven-beat runs of VT. These interventions controlled the hyperdynamic state and suppressed the ventricular ectopy. The remainder of the operative course was uneventful.Figure 2: Termination of the tachycardia after injection of adenosine.Discussion We describe a patient undergoing a CABG operation who developed an adenosine-sensitive VT. Over the past 15 years, evidence has been accumulating for the presence of at least three mechanically distinct forms of VT: reentrant, automatic, and triggered. Reentrant VT is more common in patients with structural heart disease, such as coronary artery disease and myocardial infarction [8-10]. It can be initiated by programmed stimulation and is characterized by an excitable gap, similar to a Schmitt-Erlanger entrainment circle, thought to be involved in the majority of paroxysmal supraventricular tachycardias [11,12]. Automatic VT can be induced by isoproterenol or exercise, cannot be initiated or terminated by programmed stimulation, and can be suppressed with propranolol [6]. This form of VT often occurs in diseased ventricular myocardium and probably involves abnormally low resting membrane potentials resulting in myocyte hyperexcitability [6]. Triggered VT generally occurs in younger patients without organic heart disease. It is catecholamine- and exercise-induced and can be initiated by programmed stimulation [5,7]. The focus for such triggered activity is frequently near the right ventricular outflow tract [13], and the ECG often displays a left bundle branch block morphology. The mechanism is believed to involve increased levels of Cai2+ that depolarize the myocyte and result in a lower resting membrane potential [1,6,7,14]. This state of hyperexcitability makes it more likely that the cell will reach its firing threshold when exposed to a delayed afterdepolarization. Adenosine terminates AV nodal reentrant tachyarrhythmias by a cAMP-independent effect on the conduction system [1,14,15]. More recently, adenosine has been demonstrated to terminate triggered VT, and this mechanism is proposed to involve alterations in intracellular cAMP concentrations [7]. Specifically, adenosine attenuates the catecholamine-stimulated calcium inward current, also called the slow inward, L-type calcium current, and the transient inward current, both of which have been implicated in the genesis of afterdepolarizations [15]. Adenosine binds to the A1 receptor and stimulates a guanine nucleotide-binding protein that in turn inhibits intracellular adenylate cyclase. This decreases intracellular cAMP, attenuating the calcium inward current and the transient inward current, and thereby lowers Cai2+ levels [1,5,15]. This mechanism for adenosine mimics the actions of acetylcholine, which binds to a muscarinic cholinergic receptor on the outside of the myocyte and thereby activates the same inhibitory guanine nucleotide-binding protein acted on by adenosine [7]. It follows from the above discussion that adenosine would be effective only in triggered activity due to stimulation of cAMP production, and indeed this is probably the case. For instance, adenosine is ineffective in ouabain-induced and in digitalis-induced triggered activity [16]. In these cases, Cai2+ overload is mediated by inhibition of Na,K-ATPase and not by increases in intracellular cAMP levels. The effect of adenosine on Cai2+ levels is more pronounced in the presence of exercise or catecholamine stimulation [1,5,14,15]. This is consistent with the known stimulatory effects of beta-receptor activation on adenylate cyclase. In effect, beta-receptor stimulation (e.g., exercise, hyperdynamic conditions) and adenosine have opposite effects on adenylate cyclase, cAMP, and consequently, Cai2+ levels. Thus, in the presence of catecholamine stimulation, adenosine will appear to have an enhanced effect, explaining adenosine's effectiveness in rapidly terminating catecholamine-induced VT. Adenosine has been shown to stimulate ventilatory drive [4,17]. Since increases in ventilatory drive attenuate sympathetic nerve activity by activating thoracic stretch receptors [18,19], some authors suggest that termination of VT by adenosine could be related to reactive withdrawal of sympathetic nerve traffic [7], although verification of this in the literature is lacking and the application of this concept to patients under controlled ventilation is problematic. Perhaps the antiadrenergic actions of adenosine are due to modulation of beta-adrenoreceptor affinity to agonists, although these findings are highly variable by species [20]. Finally, probably the most important influence that causes subthreshold delayed afterdepolarizations to reach threshold is a decrease in the cycle length at which action potentials occur. This decrease in cycle results in an accumulation of Cai2+ and thus cellular depolarization. Therefore, arrhythmias triggered by delayed afterdepolarizations, such as triggered VT, can be expected to be initiated by a spontaneous increase in the heart rate, as would occur in a hyperdynamic state [6]. While these remain possibilities, it is more likely that adenosine terminates VT through its known action at the cardiac A1 receptor, leading to decreased intracellular cAMP. In particular, there is in vitro evidence that adenosine attenuates catecholamine-induced activation of adenylate cyclase via A1 receptors by decreasing the ability of beta-adrenergic agonists to promote the formation of a high-affinity complex composed of the beta-agonist, receptor, and stimulatory guanine nucleotide-binding protein [20]. While the patient we describe here had coronary heart disease, both the hyperdynamic response elicited during exercise testing and the rapid termination of the VT by adenosine implicate a catecholamine-mediated, triggered mechanism for the arrhythmia. This is the first reported case of intraoperative adenosine-sensitive VT. The authors thank Douglas L. Wood, MD, Division of Cardiovascular Diseases and Internal Medicine, for his review of the manuscript and Ms. Kimberly Sankey for her secretarial assistance.

Evaluation of intravenous lidocaine for the termination of sustained monomorphic ventricular tachycardia in patients with coronary artery disease with or without healed myocardial infarction

Based on epicardial mapping, different mechanisms of termination of reentrant ventricular tachycardia by various pharmacological interventions are described. In 40 Langendorff-perfused rabbit hearts, rings of anisotropic left ventricular epicardium were made by a cryoprocedure. Sustained monomorphic ventricular tachycardia based on continuous circus movement of the impulse around the ring was induced by programmed stimulation. Increasing doses of heptanol (n = 10), potassium (n = 10), tetrodotoxin (n = 6), RP62719 (a new class III drug) (n = 4), flecainide (n = 5), and propafenone (n = 5) were administered to terminate ventricular tachycardia. Epicardial mapping (248 points) was used to study the mechanism of termination of ventricular tachycardia. In 28 of 40 hearts, ventricular tachycardia terminated because the drugs produced complete conduction block of the impulse in a segment of the reentrant pathway. In the remaining 12 hearts (heptanol, n = 2; potassium, n = 3; tetrodotoxin, n = 2; RP62719, n = 2; flecainide, n = 1; and propafenone, n = 2), termination of ventricular tachycardia occurred by collision of the circulating impulse with a spontaneous antidromic wave front reflected within the circuit. This phenomenon occurred when the circulating impulse encountered an arc of functional conduction block that did not extend along the whole width of the ring. As a result, the impulse dissociated into a continuing orthodromic circulating wave and a returning antidromic echo-wave caused by microreentry within the ring. Independent of their mechanisms of action, sodium channel blockers, electrical uncouplers, and class III drugs terminate reentrant ventricular tachycardia either by complete conduction block or by collision of the impulse with an echo-wave.

Introduction The role of MR imaging in risk stratification of patients with ventricular tachycardia (VT) and structurally normal heart is not well defined. Methods From 2005-2010, patients who presented with sustained VT or frequent nonsustained VT without echocardiographic evidence of structural heart disease were reviewed. All patients had a normal ejection fraction and no angiographic evidence of coronary artery disease. Patients received cardiac MRI and electrophysiology study (EPS) as part of their evaluation and long term outcomes were assessed. Results Thirty-two pts were evaluated for VT or nonsustained VT despite structurally normal hearts and underwent cardiac MRI with delayed gadolinium hyperenhancement (DHE) protocol to assess for scar prior to EPS. Fifteen had outflow tract VT (OTVT) morphology and eighteen presented with “non idiopathic” VT (not compatible with OTVT or fascicular VT). All 15 patients with OTVT morphology had a normal MRI and only the clinical VT was induced during EPS. Of the 18 patients with “non idiopathic” VT morphology, four patients had evidence of delayed enhancement on MRI (3 basal inferior/inferolateral LV, 1 basal to mid anterior LV). 3/4 with DHE had multiple VT (mean 2.25) induced during EPS. One patient had normal MRI yet multiple VT induced during EPS. All other patients had a negative MRI and EPS. During mean followup of 32+/-29 months, 2/4 patients (50%) with DHE on MRI, had recurrent VT requiring either ICD therapy or cardioversion. Additionally, the patient with multiple VT induced during EPS and normal MRI, also had recurrent VT at 7 months requiring cardioversion. The remaining 13 patients with non idiopathic VT morphology but normal MRI and EPS have not had recurrence. No deaths have occurred in any patient. All patients with outflow tract VT had normal MRI and have been managed medically or with ablation without reccurrence. Conclusions Cardiac MRI and EPS can help risk stratify patients with “non idiopathic” VT and structurally normal heart. Abnormal findings on MRI and EPS may identify a subgroup of patients who may be at higher risk for recurrent arrhythmic events.

Ventricular tachycardia (VT) with or without structural heart disease is uncommon but well-recognized clinically in children. With this retrospective study, we collected the data from the in-hospital pediatric patients of VT with catheter ablation therapy. The purpose of this study is to assess the acute results and the long-term outcome of catheter ablation in pediatric patients of VT in our single pediatric center. This study included 53 consecutive children (male/female=33/20, mean age=8.2±3.4 years, mean bodyweight=32.6±13.7kg). All patients underwent electrophysiological study with an attempt of catheter ablation for clinical monomorphic VT. Acute and long-term success rate of catheter ablation for the treatment of VT were compared between right and left VT as well as fascicular VT (FVT) and nonfascicular VT. There were 53 idiopathic VT forms found in the children, including FVT (n=32), outflow tract VT (n=15), papillary muscle VT (n=5), and bundle branch reentry VT (n=1). Acute success of catheter ablations for VT was achieved in 57 of all the 59 ablation procedures (97%) with VT recurrence occurred in six of 53 patients (11%). During a mean follow-up period of 29.2±21.7 months (range 1-76 months) after hospital discharge, ablations in nonfascicular VT were as successful as FVT. There was no significant difference in the success rate between the right and left VT. Catheter ablation is an effective treatment for idiopathic VT in children. The acute and long-term success rates of catheter ablation for idiopathic VT in pediatric patients with normal heart structure are satisfying.