Effects of Verapamil on Ventricular Tachycardia Induced by Ouabain in Guinea Pigs

Calcium ions appear to play a central role in the development of ventricular arrhythmias associated with digitalis intoxication. Therefore, the effects of the calcium channel antagonist, verapamil, on ouabain-induced ventricular tachycardia were investigated. Ventricular tachycardia (three or more consecutive wide QRS complexes) was induced in guinea pigs by intravenous infusion of ouabain (1 microgram/min) and bursts of rapid ventricular stimulation. Of seven guinea pigs given the infusion of ouabain, all developed ventricular tachycardia at a dose of 82 +/- 17 micrograms/kg (mean +/- SD) and none developed heart block or asystole. Eight guinea pigs were treated with verapamil (2 micrograms/min for 30 minutes) prior to exposure to ouabain. Of those eight animals, only two developed ventricular tachycardia but six developed heart block or asystole at a significantly higher dose of ouabain (154 +/- 47 micrograms/kg). None of three control guinea pigs given an infusion of normal saline for 90 minutes developed ventricular tachycardia. These results show that pretreatment with verapamil inhibits ouabain-induced ventricular tachycardia in guinea pigs. Combined treatment with verapamil and ouabain is associated with a high incidence of heart block and asystole, which may limit the usefulness of verapamil.     

Procainamide in the Induction and Perpetuation of Ventricular Tachycardia in Man

The effects of a single intravenous infusion of 750 mg of procainamide was studied in 12 patients with symptomatic chronic recurrent ventricular tachycardia in whom arrhythmias could reproducibly be initiated and terminated by programmed electrical stimulation of the heart. Sustained ventricular tachycardia was induced in 6 patients and non-sustained tachycardia was induced in the remaining 6 patients during control studies. Following procainamide (plasma level 10.3 +/- 3.7 mcg/ml), ventricular tachycardia could be induced in 10/12 patients, sustained in 4 patients and non-sustained in the remaining 6 patients. In 8/12 patients (66%), induction of ventricular tachycardia was facilitated as demonstrated by: (1) tachycardia zone was widened in 4 patients and was unchanged in another 3 patients; (2) non-sustained ventricular tachycardia was sustained ventricular tachycardia in one patient. the ventricular tachycardia had a faster rate and a different QRS morphology; (3) in 4 patients tachycardia was inducible with a lesser number of extrastimuli and/or by spontaneously occurring ventricular premature depolarization and; (4) increase of the number of induced ventricular responses of non-sustained ventricular tachycardia. In 4/12 patients (33%), procainamide abolished or modified the induction of ventricular tachycardia as demonstrated by: (1) inability to induce ventricular tachycardia in 2 patients; (2) narrowing of the tachycardia zone and conversion from sustained into non-sustained ventricular tachycardia (one patient) and; (3) decrease in the number of induced ventricular responses in one patient. The response to procainamide could not be predicted from rates of spontaneous ventricular tachycardia, induced ventricular tachycardia during control studies, degree of slowing of ventricular tachycardia or from prolongation of the coupling interval after procainamide. These results suggest that instead of abolishing the arrhythmia, procainamide in frequently employed doses in patients with chronic recurrent ventricular tachycardia can facilitate its initiation sometimes at even faster rates. Patients not responsive to the usual doses of procainamide should undergo acute drug trials to determine the optimal dose/drug levels.     

Management of Nonsustained Ventricular Tachycardia Guided By Electrophysiological Testing

Two hundred eighty patients with spontaneous nonsusfained ventricular tachycardia were treated based on the results of electrophysiological testing. Seventy-nine patients had no evidence of structural heart disease, 134 had coronary artery disease, 43 had idiopathic dilated cardiomyopathy, and 24 patients had miscellaneous types of heart disease. Sustained monomorphic ventricular tachycardia was induced during electrophysiological testing in the drug free state in 52 of 280 patients (19%). Ventricular tachycardia was induced more frequently in patients with coronary artery disease (32%) than in any of the other groups (P < 0.001). The patients with inducible sustained monomorphic ventricular tachycardia underwent a mean of 1.9 ± 1.3 drug trials. Twenty-five patients had the induction of ventricular tachycardia suppressed by pharmacological therapy and were treated with the drug judged to be effective during electropharmacological testing. Twenty-seven patients continued to have inducible sustained monomorphic ventricular tachycardia despite antiarrhythmic therapy and were discharged on the drug that made induced ventricular tachycardia best tolerated. Forty-five of 280 patients (16.1%) died during a mean follow-up period of 19.6 ± 14.4 months, There were 15 sudden cardiac deaths, 21 nonsudden cardiac deaths, 6 noncardiac deaths, and 3 deaths that could not be classified. Sudden cardiac death mortality was lowest in the patients without structural heart disease (0% at 2 years), intermediate in the patients with coronary artery disease and miscellaneous heart disease (4% al 2 years), and highest in the patients with idiopathic dilated cardiomyopathy (13% at 2 years; P < 0.01 for pairwise comparisons). No patient treated with a drug that had suppressed the induction of sustained ventricular tachycardia died suddenly during the follow-up period whereas four of 27 patients who were discharged on “ineffective antiarrhythmic drugs” and 11 of 228 patients without inducible sustained ventricular tachycardia experienced sudden cardiac death during the follow-up period. By multivariate analysis, ejection fraction and inducible ventricular tachycardia during the predischarge eiectrophysiological test were independent predictors of sudden cardiac death. In conclusion, in patients with spontaneous nonsustained ventricular tachycardia: (1) Arrhythmia inducibility varies depending on the underlying heart disease. Ventricular tachycardia is most often inducible in patients with coronary artery disease and least often in patients without structural heart disease; (2) With the exception of patients with idiopathic dilated cardiomyopathy, management of patients with nonsustained ventricular tachycardia guided by electrophysiological testing appears to result in a low incidence of sudden cardiac death although effects on total mortality are less impressive; and (3) Patients with idiopathic dilated cardiomyopathy and patients with other heart diseases who continue to have inducible ventricular tachycardia despite antiarrhythmic drug therapy are at substantial risk of sudden cardiac death.     

Recurrent Ventricular Tachycardia Responsive to Verapamil

We describe five young patients with recurrent ventricular tachycardia in the absence of organic heart disease. In all patients tachycardia could be terminated or prevented with verapamil. Tachycardia in four patients was very similar, with a QRS pattern of right bundle branch block and left axis deviation. Electrophysiology studies in two patients showed that VT was inducible in one patient (rapid atrial or ventricular pacing, ventricular extrastimuli) but not in the other. The clinical and electrocardiographic similarities in these patients suggest that their ventricular tachycardias may share a common pathophysiology and may be dependent on slow channel activity.     

Ventricular Tachycardia

Ventricular tachycardia most often is a manifestation of intrinsic heart disease or digitalis intoxication. Differential diagnosis is of utmost importance in planning treatment.

Intravenous administration of procaine amide hydrochloride is the treatment of choice. However, if the arrhythmia occurs without underlying heart disease and is well tolerated, orally administered therapy is preferable to that given intravenously. Digitalis is no longer contraindicated in ventricular tachycardia unless intoxication with this drug is suspected.

NaEDTA has proved effective in digitalis-induced ventricular tachycardia.     

Spontaneous Deterioration of Atrioventricular Nodal Reentrant Tachycardia to Polymorphic Ventricular Tachycardia in the Absence of Heart Disease

Atrioventricular nodal reentrant tachycardia (AVNRT) is usually associated with a good prognosis. This is a case of a 57‐year woman who presented with supraventricular tachycardia that spontaneously deteriorated to polymorphic ventricular tachycardia (PVT). The PVT terminated without treatment after 16 seconds. Extensive cardiac evaluation including echocardiography, stress testing, coronary angiography, and cardiac magnetic resonance imaging did not reveal any structural heart disease. Electrophysiology testing demonstrated typical AVNRT which was successfully treated with cryoablation. The clinical ventricular tachycardia could not be reproduced despite the use of an aggressive induction protocol and isoproterenol. Postablation, exercise treadmill testing did not provoke any tachyarrhythmia. The patient is doing well 13 months later. In summary, we present the rare finding of a moderately fast, typical AVNRT degenerating to a long run of PVT, in the absence of any detectable heart disease or other etiology for PVT. (PACE 2011; 34:e14–e17)     

Adenosine and Verapamil-Sensitive Ventricular Tachycardia Originating From the Left Ventricle: Radiofrequency Catheter Ablation

A ventricular tachycardia (VT) with right bundle branch block (RBBB) QRS morphology and left axis originating from the inferoapical segment of the left ventricle is described in a 49-year-old man without structural heart disease. This VT could be initiated during isoproterenol infusion and was terminated with intravenous administration of adenosine and verapamil. Radiofrequency ablation eliminated the tachycardia. Previous reports have suggested reentry as the mechanism for a verapamil-sensitive VT with this ECG morphology, while cAMP-mediated triggered activity has been proposed as a mechanism for VTs sensitive to adenosine. The latter more typically arise in the right ventricular outflow tract. The electrophysiological and electropharmacological characteristics of the tachycardia in this patient suggest that this VT morphology is not specific for a mechanism but rather for the location of the site of origin.     

室性心动过速的血流动力学研究

用分级递增刺激方式致健康犬不同部位和不同频率的室性心动过速（ＶＴ），应用多普勒超声心动图和心导管同步测量技术测得到一系列指标对ＶＴ的血流动力学进行系统研究。结果示：（１）不同心室起源部位的ＶＴ对血流动力学影响的程度不同，以左，右室心尖起源的ＶＴ影响的程度最小，左，右室侧壁者次之，以左，右室流出道起源的ＶＴ影响程度最大：（２）ＶＴ频率超过基础心率≤６０时，同对照值比较，各项血流动力学指标无显著变化。     

Comparison of intravenous ibutilide vs. propafenone for rapid termination of recent onset atrial fibrillation

This study was to evaluate the efficacy and safety of ibutilide and propafenone given intravenously in converting recent onset atrial fibrillation (AF). Eighty-two consecutive patients with AF (onset in 2 h to 90 days) were randomly assigned to receive two 10-min infusions, 10 min apart, of either ibutilide (1 mg) or propafenone (70 mg). The treatment was considered successful if sinus rhythm occurred within 90 min after the beginning of infusion. Ibutilide had a significantly higher rate of cardioversion than propafenone (70.73 vs. 48.78%, p = 0.043). The patients with shorter AF duration or smaller left atrium diameter had a higher success rate. Nonsustained monomorphic ventricular tachycardia was the most serious adverse effect of ibutilide in 9.76% of patients, and hypotension and heart pause were the major serious adverse events in 17.07% of patients treated with propafenone. Ibutilide is more effective than intravenous propafenone for the cardioversion of recent onset AF, and the adverse effects are rare and transient.     

Propafenone for the treatment of refractory complex ventricular ectopic activity

The results of therapy with propafenone were evaluated in 45 patients with complex ventricular ectopic activity that had been refractory to a mean of 3.8 antiarrhythmic drugs. The cardiac diagnoses were ischemic heart disease (in 16 patients), cardiomyopathy (in 7), mitral valve prolapse (in 7), mitral valve prolapse (in 7), idiopathic ventricular ectopic beats (in 6), valvular heart disease (in 5), and hypertension (in 4). The frequency of ventricular ectopic beats was established after therapy with antiarrhythmic agents had been discontinued. Patients then received propafenone during a dose-ranging protocol. An effective response was defined as a reduction in total ventricular ectopic beats of 80% or more. During dose ranging, therapy failed in four patients because of side effects, in eight because of a reduction in ventricular ectopic beats of less than 80%, and in three because of an aggravation of the arrhythmia. Thirty patients had a reduction in total ventricular ectopic beats of 80% or more. During a mean follow-up of 12.4 months, therapy failed in 1 patient because of sustained ventricular tachycardia and in 7 because of intolerable side effects; 22 patients continued to receive propafenone. PR and QRS intervals were significantly prolonged (P = 0.001), but the corrected QT interval and the heart rate were unchanged. The mean trough plasma level of propafenone associated with an effective response was 756 ng/ml, and that associated with intolerable side effects was 920 ng/ml. Thus, in patients with refractory complex ventricular ectopic beats, propafenone was effective and well tolerated initially in 67% of patients and during long-term administration in 49%, and toxicity was minor in most patients.     

Ventricular Tachycardia and Ventricular Fibrillation in Patients with Short P-R Intervals and Narrow QRS Complexes

Eleven patients with short P-R Intervals and narrow QRS complexes had ventricular tachycardia due to organic heart disease: mitral valve prolapse with mitral insufficiency (2 patients); alcoholic (?) cardiomyopathy (2 patients); and coronary artery disease (7 patients). Intracardiac studies showed short A-H intervals during sinus rhythm in all cases. The onset of ventricular fibrillation (which, to our knowledge, has not been observed in patients having short P-R and A-H intervals coexisting with narrow QRS complexes) was documented in 4 cases. Only 1 patient (with quinidine syncope) had been premedicated. In the 3 other patients the episodes of ventricular fibrillation appeared during bouts of atrial fibrillation with rapid ventricular rates which could have been an expression of the “enhanced A-V conduction” that had been manifested in sinus beats by short P-R and A-H intervals. In clinical settings and physiological conditions proven to be hemodynamicaliy unstable (such as transient ischemia or acute myocardial infarction) these rapid ventricular rates could have led to ventricular fibrillation; directly because of the R-on-T phenomenon, and/or indirectly due to decreased coronary perfusion. Ventricular tachycardia and ventricular fibrillation due to organic heart disease probably occur more often than suggested by the few reported cases in the literature. Its significance, however, has to be clarified by further prospective studies     

Repetitive Nonsustained Monomorphic Ventricular Tachycardia Aborted by Methoxamine and Sleep "Heart Rate Dependent Ventricular Tachycardia"

Methoxamine, an alpha adrenoreceptor agonist, and sleep abolished repetitive nonsustained monomorphic ventricular tachycardia in a 41-year-old man without detectable underlying heart disease. Detailed pacing studies revealed that the occurrence of ventricular tachycardia was totally dependent on the basic heart rate. Sleep and the alpha adrenoreceptor agonist abolished the ventricular tachycardia by slowing the basic heart rate. Verapamil, propranolol, and disopyramide were able to decrease the upper limit of the tachycardia-initiating heart rate, but none of them were able to increase the lower limit (75/min). Failure to increase the lower limit of the tachycardia-initiating heart rate was a major reason why these conventional antiarrhythmic drugs were unable to suppress his daytime episodes of repetitive ventricular tachycardia.     

Electrophysiologic, inotropic and antiarrhythmic effects of propafenone, 5-hydroxypropafenone and N-depropylpropafenone

We compared the electrophysiologic, inotropic and antiarrhythmic properties of propafenone and two metabolites, 5-hydroxy (5-OH) propafenone and N-depropyl (N-DP) propafenone. In 18 canine Purkinje fibers with normal maximum diastolic potentials, all drugs (1 x 10(-8) to 1 x 10(-5) M) reduced action potential amplitude and duration. However, propafenone and 5-OH propafenone reduced Vmax in a use-dependent fashion at a lower concentration than N-DP propafenone. In 16 Purkinje fibers, slow response action potentials were induced by 22 mM K+ and isoproterenol, 1 x 10(-6) M. Vmax was comparably reduced by all compounds at 1 x 10(-5) M, but action potential amplitude was not affected by 5-OH propafenone. In 16 other Purkinje fibers in which automaticity at low levels of membrane potential was induced by BaCl2 (0.25 mM), only 5-OH propafenone was effective in slowing the automatic rate at therapeutic concentrations (3 micrograms/ml). In 15 guinea pig papillary muscles, all three drugs had negative inotropic effects at concentrations greater than or equal to 1 x 10(-6) M. In conscious dogs with sustained ventricular tachycardia 24 hr after infarction, we injected propafenone or a metabolite through an atrial cannula. At similar plasma levels, neither propafenone (n = 6) nor N-DP propafenone (n = 6) suppressed the arrhythmia, whereas 5-OH propafenone eliminated ventricular tachycardia in four of six dogs, and was more effective against monomorphic than polymorphic ventricular tachycardia. Hence, the two major metabolites of propafenone have important electrophysiologic effects, and 5-OH propafenone is more potent than the parent compound as a antiarrhythmic drug in the 24-hr Harris dog.     

Adenosine Sensitive Left Ventricular Tachycardia

Presented here is a 39-year-old male patient with no structural heart disease but a ventricular tachycardia with right bundle branch block morphology and right axis deviation, which is responsive to adenosine. The ventricular tachycardia was initiated by ventricular pacing, shown to originate from the mid-anterior free wall region of the left ventricle and terminated by adenosine. Radiofrequency current application at a site where presumed P potentials were recorded eliminated the tachycardia, a finding that suggests that the origin of the tachycardia may be closely related to the anterior fascicle.     

Radiofrequency Catheter Ablation of Sinus Node Reentrant Tachycardia

Sinus node reentrant tachycardia is a relatively uncommon (5%-5%) form of recurrent paroxysmal supraventricular tachycardia (SVT). We describe a case of symptomatic sinus node reentrant tachycardia in a 67-year-old male with ischemic heart disease, congestive heart failure, and depressed ventricular function. Adenosine administered during an electrophysiology study caused prolongation of the tachycardia cycle length due to atrial cycle length prolongation (without atrio-His prolongation) prior to tachycardia termination. Right atrial mapping revealed the earliest site of atrial activation in the high lateral right atrium just below the superior vena cava. Low energy (10 and 20 W) radiofrequency lesions were applied ai this site with termination of the tachycardia within 3 seconds of radiofrequency energy delivery. Tachycardia could not be reinduced after delivery of the radiofrequency lesions. The sinus node function immediately and 6 weeks after radiofrequency catheter ablation remained normal and the patient was without clinical recurrence of SVT. Mapping of sinus node reentrant tachycardia and elimination of the reentrant circuit with radiofrequency catheter ablation is possible without causing sinus node dysfunction. Adenosine causes prolongation of the atrial cycle length followed by termination of sinus node reentrant tachycardia.     

Multiform Ventricular Tachycardia

Electrophysiological studies were performed in three patients with chronic recurrent ventricular tachycardia (VT) associated with coronary artery disease. In each case the ventricular origin of the tachycardia was confirmed and induction of tachycardia by programmed stimulation suggested a re-entry mechanism. Multiple types of ventricular tachycardia were observed which differed in cycle length, QRS morphology, timing of local epicardial and endocardial ventricular electrograms and the use of the specialized conduction system for propagation. There was evidence of one or more re-entry circuits arising in or near previously infarcted areas, with features of cycle length alternation, change in exit points and variations in subsequent conduction through the myocardium and specialized conduction tissues. These findings suggest multiform VT can be due to a number of factors. A modified surgical approach is recommended for management of medically refractory VT when there is evidence of multiple types.     

Adenosine-Sensitive Atrial Tachycardia

Limited data suggest that adenosine termination of atrial tachycardia is uncommon. To investigate further the effect of adenosine on atrial tachycardia, adenosine (6–12 mg) was administered during sustained atrial tachycardia in 17 patients. All patients underwent electrophysiological study to exclude other mechanisms of supraventricular tachycardia. Mean patient age was 51 ± 20 years (range 18–82 years). Seven patients had no structural heart disease. The mean atrial tachycardia cycle length was 390 ± 80 msecs (range 260–580). Sustained atrial tachycardia was induced with atrial extrastimuli in 8 patients, and was either incessant at baseline or developed spontaneously during isoproterenol infusion in 9 patients. Adenosine terminated atrial tachycardia in 3 patients (18%), transiently suppressed atrial tachycardia in 4 patients (23%), and produced AV block without affecting tachycardia cycle length in the remaining 10 patients. Adenosine sensitivity was observed in 3 of 8 patients with tachycardias initiated and terminated by atrial extrastimuli, and in 4 of 9 patients with spontaneous, but not inducible tachycardias including 3 of 4 patients with isoproterenol facilitated tachycardias. Of multiple clinical and electrophysiological variables examined as potential predictors of adenosine sensitivity, only isoproterenol facilitation of spontaneous or inducible sustained tachycardia predicted adenosine sensitivity (P = 0.02). These observations suggest that adenosine-sensitive atrial tachycardia may be more common than previously recognized. Adenosine sensitivity does not appear to be specific for tachycardia mechanism and cannot be predicted by response to pacing. Atrial tachycardias dependent on β-adrenergic stimulation are most likely to be terminated by adenosine.     

Unexpected Coexistence of Supraventricular and Ventricular Tachycardia in Patients with Syncope

The incidence of multiple, inducible sustained arrhythmias during electrophysiologic studies is unknown. We have identified five patients who had several sustained tachycardias, some of which were not previously recognized clinically. Three patients had documented sustained supraventricular tachycardia (one of these also had nonsustained ventricular tachycardia) and two had documented sustained ventricular tachycardia. The clinically documented tachycardia was successfully reproduced in all cases; however, the three cases of supraventricular tachycardia also had sustained ventricular tachycardia initiated, and the two cases of ventricular tachycardia also had sustained supraventricular tachycardia, which had not previously been seen. The underlying common denominators for all five patients were poor left ventricular function due to ischemic heart disease and a history of syncope. In one case of clinical supraventricular tachycardia, the second sustained tachycardia appeared following drug therapy (procainamide), which seemed to convert nonsustained to sustained ventricular tachycardia. In another patient with clinical ventricular tachycardia, the supraventricular tachycardia was also initiated following drug therapy (indecainide). We conclude that: (1) patients with syncope may have multiple arrhythmic etiologies and (2) complete electrophysiologic evaluation, during control studies as well as serial drug studies, are important in the management of these patienls.     

Safety of Transvenous Low Energy Cardioversion of Atrial Fibrillation in Patients with a History of Ventricular Tachycardia: Effects of Rate and Repolarization Time on Proarrhythmic Risk

The objective of this study was to assess the safety and efficacy of transvenous low energy cardioversion of atrial fibrillation in patients with ventricular tachycardia and atrial fibrillation and to study the mechanisms ofproarrhythmia. Previous studies have demonstrated that Cardioversion of atrial fibrillation using low energy, R wave synchronized, direct current shocks applied between catheters in the coronary sinus and right atrium is feasible. However, few data are available regarding the risk of ventricular proarrhythmia posed by internal atrial defibrillation shocks among patients with ventricular arrhythmias or structural heart disease. Atrial defibrillation was performed on 32 patients with monomorphic ventricular tachycardia and left ventricular dysfunction. Shocks were administered during atrial fibrillation (baseline shocks), isoproterenol infusion, ventricular pacing, ventricular tachycardia, and atrial pacing. Baseline shocks were also administered to 29 patients with a history of atrial fibrillation but no ventricular arrhythmias. A total of 932 baseline shocks were administered. No ventricular proarrhythmia was observed after well-synchronized baseline shocks, although rare inductions of ventricular fibrillation occurred after inappropriate T wave sensing. Shocks administered during wide-complex rhythms (ventricularpacing or ventricular tachycardia) frequently induced ventricular arrhythmias, but shocks administered during atrial pacing at identical ventricular rates did not cause proarrhythmia. The risk of ventricular proarrhythmia after well-synchronized atrial defibrillation shocks administered during narrow-complex rhythms is low, even in patients with a history of ventricular tachycardia. The mechanism of proarrhythmia during wide-complex rhythms appears not to be related to ventricular rate per se, but rather to the temporal relationship between shock delivery and the repolarization time of the previous QRS complex.     

Electrophysiological Observations During QRS Alternans in a Patient with Incessant Tachycardia

Electrophysiological observations during preoperative and intraoperative study of a 46-year-old patient with incessant ventricular tachycardia and QRS alternans demonstrated a potential mechanism for this electrocardiographic finding. During QRS alternans, conduction delay (or block) was recorded from the site of origin of the tachycardia, high on the anterior septum to the His bundle: After procainamide infusion, the tachycardias slowed and, concurrent with the disappearance of QRS alternans, conduction from the site of tachycardia origin to the His bundle could no longer be demonstrated.