Paired comparisons of efficacy of intravenous and oral procainamide in patients with inducible sustained ventricular tachyarrhythmias

Thirty-eight patients who had inducible sustained ventricular tachycardia during baseline programmed electrical stimulation underwent electrophysiologic testing after both intravenous and oral administration of procainamide. Each had presented clinically with documented sustained ventricular tachycardia or out of hospital cardiac arrest not associated with acute myocardial infarction. In 23 patients (61%) (Group I) the arrhythmia became noninducible during an intravenous infusion of procainamide. Oral procainamide was subsequently administered and retesting was carried out after dose titration to match plasma concentration at the end of the intravenous study. Among the 23 patients in Group I the mean (+/- SD) plasma procainamide level was 7.2 +/- 2.8 micrograms/ml after intravenous dosing and 7.9 +/- 2.5 micrograms/ml after oral dosing (p = 0.09). In 15 (65%) of the 23 patients, sustained ventricular arrhythmia was inducible on oral therapy with comparable plasma procainamide levels (intravenous = 6.3 +/- 2.1 micrograms/ml, oral = 7.5 +/- 2.1 micrograms/ml). The other eight patients (35%) had concordant responses to repeat testing with comparable intravenous (mean 9.0 +/- 3.3 micrograms/ml) and oral (8.8 +/- 3.1 micrograms/ml) plasma procainamide levels. In the additional 15 patients (Group II) sustained ventricular tachyarrhythmia remained inducible on intravenous procainamide therapy and the patients were retested on oral therapy with similar plasma concentration (p = 0.05). In seven patients (47%) sustained ventricular tachyarrhythmia was noninducible on treatment with oral procainamide (mean plasma level 7.6 +/- 2.7 micrograms/ml) after failure of intravenous procainamide (mean plasma level 10.3 +/- 2.3 micrograms/ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

Suppressive effect of nicorandil in ventricular arrhythmias after reperfusion therapy in patients with acute myocardial infarction

BACKGROUND: Nicorandil is reported to inhibit reperfusion arrhythmias in patients with acute myocardial infarction (AMI), but few studies have counted ventricular arrhythmias with Holter electrocardiograms in patients treated with nicorandil following AMI reperfusion. OBJECTIVES: In the present study, we examined the effects of nicorandil by investigating the occurrence of ventricular arrhythmia with Holter electrocardiogram monitoring after percutaneous coronary intervention with acute myocardial infarction. METHODS: Forty patients with AMI who underwent successful percutaneous coronary intervention (PCI) were enrolled and randomly assigned to nicorandil or placebo groups. Following PCI, nicorandil was infused intravenously at 6 mg/hr for 24 hr, with Holter electrocardiogram monitoring. Patients with 100 or more premature ventricular contractions (PVCs) over the 24-hour period were studied. The total number of PVCs, frequency of occurrence of ventricular tachycardia, and clinical characteristics were compared between the two groups. RESULTS: Fourteen patients in the nicorandil group and 12 patients in the placebo group exhibited 100 or more PVCs over the 24-hour period. Lesion characteristics and procedural factors did not differ between the two groups. Fewer PVCs were counted in the nicorandil group than in the placebo group(144.6 +/- 106.5 vs 286.8 +/- 159.1 beats/day, p = 0.012). The frequency of coupled PVCs was lower in the nicorandil group (6.9 +/- 6.9 vs 16.3 +/- 12.8 beats/day, p = 0.025). Although the frequency of ventricular tachycardia did not differ between the two groups, ventricular tachycardia duration was significantly shorter in the nicorandil group (3.73 +/- 2.30 vs 8.34 +/- 7.45 sec, p = 0.03). CONCLUSIONS: Our study indicates nicorandil inhibits ventricular arrhythmias following PCI for patients with AMI. Nicorandil treatment following PCI for AMI is convenient and may reduce the rate of cardiac events by inhibiting ventricular arrhythmias, thereby potentially improving the prognosis.     

Amiodarone: correlation of serum concentration with suppression of complex ventricular ectopic activity

Although amiodarone has been used for the suppression of complex ventricular arrhythmias since the early 1970s, there is a paucity of information regarding the relation of serum concentration to arrhythmia suppression. To investigate this relation, 25 patients receiving chronic amiodarone therapy for complex ventricular arrhythmias were retrospectively studied. At each visit a blood sample for determination of trough serum amiodarone concentration and a 24-hour 2-channel ambulatory electrocardiogram (ECG) were obtained. Dosage was adjusted, based on the ambulatory ECG, to maintain arrhythmia suppression at the lowest possible amiodarone dose and, hence, because of the extremely long half-life of amiodarone, patients were rarely in a true steady state. Over 17 months, 218 ambulatory ECGs with corresponding serum samples were analyzed. Negative correlations between serum amiodarone concentration and the frequencies of premature ventricular complexes (PVCs), paired PVCs and ventricular tachycardia were found (p less than 0.005, p less than 0.005 and p less than 0.05, respectively). No correlations existed between amiodarone dose and these arrhythmias. Trough serum amiodarone concentrations greater than 2.0 micrograms/ml were associated with significant reductions in the frequencies of PVCs (p less than 0.01) and paired PVCs (p less than 0.02) when compared with serum concentrations below this level. A reduction in ventricular tachycardia was seen with serum concentrations greater than 1.5 micrograms/ml (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of diuretic therapy on ventricular arrhythmias in hypertensive patients with or without left ventricular hypertrophy

Recent studies have suggested that hypertensive patients with ECG evidence of left ventricular hypertrophy (LVH) may have increased risk of sudden death when treated with diuretics. In the present study echocardiography was used as a more sensitive index for the presence of LVH. Thirty-one patients with uncomplicated hypertension underwent 48-hour ambulatory ECG monitoring both before any treatment and after 4 weeks of hydrochlorothiazide, (HCTZ), 100 mg daily. In 18 patients with left ventricular posterior wall thickness (LVPWT) greater than or equal to 13 mm (average = 14.4 +/- 0.2 mm) on echocardiogram, plasma potassium decreased from 4.1 +/- 0.3 to 3.3 +/- 0.4 mEq/L with HCTZ (p less than 0.01). Premature ventricular contractions (PVCs) averaged 5.7 +/- 9.9/hr at baseline and 7.1 +/- 16.6/hr following HCTZ (p = NS). The total number of couplets was 29 before and 13 after HCTZ, while four brief runs of ventricular tachycardia occurred only before treatment. In the remaining 13 patients with LVPWT less than or equal to 12 mm (average = 11.2 +/- 0.1 mm), plasma potassium decreased from 4.1 +/- 0.3 to 3.4 +/- 0.5 mEq/L with HCTZ (p less than 0.01). The average number of PVCs was 4.3 +/- 8.0/hr after HCTZ (p = NS). One couplet and one 3-beat run of ventricular tachycardia occurred before and one 3-beat run of ventricular tachycardia after HCTZ. Although more complex arrhythmias were noted in the LVH group, the differences were not statistically significant. These results indicate that thiazide therapy does not increase ventricular arrhythmias either in patients with or without LVH.     

Influence of lidocaine on human muscle sympathetic nerve activity during programmed electrical stimulation and ventricular tachycardia.

Lidocaine directly affects conduction and refractoriness of ventricular myocardium, and may also indirectly affect these electrophysiologic properties by inhibition of cardiac sympathetic nerve traffic. Both effects may play important roles in preventing ventricular arrhythmias in humans. To determine if lidocaine has a direct effect on sympathetic nerve activity, the effects of a 100 mg lidocaine bolus followed by a 2 mg/min infusion of lidocaine on muscle sympathetic nerve activity was assessed in seven patients during programmed ventricular stimulation with single extrastimuli (premature ventricular contractions [PVCs]) in sinus rhythm, and in seven patients during induced hemodynamically stable monomorphic ventricular tachycardia. During single extrastimuli, the mean (+/- SEM) area of PVC-associated bursts of sympathetic nerve activity was unaffected by lidocaine (1101 +/- 16 units pre-lidocaine versus 1075 +/- 19 units following lidocaine; p = 0.30). Likewise, the transient decrease in blood pressure with induced PVCs was similar before and after lidocaine infusion (p = 0.46). In seven patients with induced monomorphic ventricular tachycardia, tachycardia cycle length did not change after the lidocaine bolus (393 +/- 18 versus 399 +/- 17 msec; p = 0.34) but increased during lidocaine maintenance infusion (428 +/- 17 msec; p = 0.01). After induction of ventricular tachycardia, systolic pressure decreased from 150 +/- 6 to 117 +/- 9 mm Hg at 1 minute of tachycardia, to 109 +/- 6 mm Hg during the lidocaine bolus, and rebounded to 126 +/- 8 mm Hg during the lidocaine maintenance infusion (p = 0.04, bolus versus infusion).(ABSTRACT TRUNCATED AT 250 WORDS)     

Theophylline and salbutamol in combination in patients with obstructive pulmonary disease and concurrent heart disease: effect on cardiac arrhythmias

We compared the frequency and severity of cardiac arrhythmias during combined oral theophylline and inhaled salbutamol vs. salbutamol therapy alone in 18 patients with moderate to severe chronic obstructive pulmonary disease who had concurrent cardiac disease. Seventeen patients showed at least one supraventricular premature complex (SVPC) on the 24-h ECG recording when receiving salbutamol alone: eight patients had isolated SVPCs, less than 10/h; five patients had greater than or equal to 10 SVPCs/h; eight patients showed runs of supraventricular tachycardia or paroxysmal atrial fibrillation. Seventeen patients also had at least one ventricular premature complex: seven patients had less than 10 isolated PVCs/h, five patients greater than or equal to 10 PVCs/h; eight patients had paired or multifocal PVCs and one patient a run of ventricular tachycardia. The addition of oral theophylline at an average dose of 600 mg in the evening (blood concentrations showed a mean maximum of 13.4 +/- 4.0 (SD) and minimum of 5.5 +/- 2.9 mg/l) had no influence on the frequency or severity of either ventricular or supraventricular arrhythmias. Thus, cardiac arrhythmias are very common in patients with chronic obstructive pulmonary disease and concomitant heart disease, but oral theophylline added to a regimen of salbutamol does not seem to affect the occurrence or severity of arrhythmias.     

Occurrence of ventricular arrhythmias in patients receiving acute and chronic infusions of milrinone

Milrinone is a promising new inotrope, but its arrhythmogenic potential has not been defined. We monitored ventricular arrhythmias during a 24-hour baseline and 48-hour milrinone infusion period in 12 patients with chronic heart failure. Patients were characterized by a mean age of 58 years and a left ventricular ejection fraction of 21%. Nine (75%) were male, nine had primary idiopathic dilated cardiomyopathy, and three had coronary artery disease. None had a history of cardiac arrest or sustained ventricular tachyarrhythmia. Milrinone was given as a loading dose (mean 53 micrograms/kg/10 min; range 37.5 to 75) followed by a 48-hour maintenance infusion (mean 0.53 micrograms/kg/min; range 0.25 to 0.75). Acutely, cardiac index increased by 27% and pulmonary wedge pressure decreased by 30% during milrinone; changes were maintained during continued therapy. Ventricular arrhythmia response was variable, with no significant overall difference. However, a trend toward increased ectopic activity was noted. No sustained tachyarrhythmias occurred. Mean frequency of premature ventricular complexes (PVCs) was 87 +/- 48 PVCs/hr (x +/- SEM) during baseline monitoring and 141 +/- 69/hr following infusion of the drug (p = 0.08). Mean frequency of couplets was 6.0 +/- 4.9/hr before drug infusion and 14.3 +/- 11.0/hr during infusion (p = 0.21). Mean frequency of runs was 0.9 +/- 0.8/hr before and 2.7 +/- 2.4/hr during drug infusion (p = 0.29). Two patients met criteria for proarrhythmia (increased PVCs of greater than 4x and/or repetitive forms of greater than 10x. However, neither proarrhythmia patient required reduction in the dosage of milrinone or additional antiarrhythmic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical and electrophysiological spectrum of idiopathic ventricular outflow tract arrhythmias.

OBJECTIVES: This study sought to compare and contrast the clinical and electrophysiological characteristics of outflow tract arrhythmias. BACKGROUND: Idiopathic ventricular outflow tract arrhythmias manifest clinically in 3 forms: 1) paroxysmal sustained monomorphic ventricular tachycardia (SMVT), 2) repetitive nonsustained ventricular tachycardia (NSVT), or 3) premature ventricular contractions (PVCs). Although these arrhythmias have a similar site of origin, it is unknown whether they share a common mechanism or similar clinical features. METHODS: A total of 127 patients (63 female [50%], mean age 51 +/- 15 years) were evaluated for outflow tract arrhythmias. RESULTS: A total of 36 (28%) presented with the index clinical arrhythmia of SMVT, 46 (36%) with NSVT, and 45 (35%) with PVCs. The sites of origin of the arrhythmias were similar among the 3 groups, occurring in the right ventricular outflow tract in 82%. Sustained ventricular tachycardia was more likely to be induced during exercise in the SMVT (10 of 15 patients [67%]) than NSVT or PVCs groups (p < 0.01). Sustained outflow tract ventricular tachycardia was induced at electrophysiology study in 78% of SMVT patients, 48% of NSVT patients, and 4% of PVCs patients. Adenosine was similarly effective in all 3 groups (p = NS). CONCLUSIONS: Patients with outflow tract arrhythmias can be differentiated based on the subtype of arrhythmia. However, the observation that approximately 50% of patients with NSVT and approximately 5% of patients with PVCs have inducible sustained ventricular tachycardia that behaves in an identically unique manner to those who present with sustained ventricular tachycardia (e.g., adenosine-sensitive) suggests that rather than representing distinct entities, outflow arrhythmias may be considered a continuum of a single mechanism.     

Comparative electrophysiologic effects of intravenous and oral procainamide in patients with sustained ventricular arrhythmias

Thirty-three patients with sustained ventricular arrhythmias underwent electrophysiologic testing after intravenous and again after oral procainamide administration. Two groups were identified: group 1 included 15 patients with concordant serum procainamide concentrations with less than a 3 micrograms/ml difference after intravenous (mean 8.6 +/- 2.7) and oral (mean 8.8 +/- 2.7) procainamide administration, with mean N-acetylprocainamide concentrations of 1.0 +/- 0.6 and 6.2 +/- 2.8 micrograms/ml, respectively. Group 2 included 18 patients with discordant serum procainamide concentrations after intravenous (mean 9.5 +/- 5.9 micrograms/ml) and oral (mean 14.1 +/- 5.2 micrograms/ml) procainamide, with mean N-acetylprocainamide concentrations of 0.9 +/- 0.5 and 10.7 +/- 5.7 micrograms/ml, respectively. In group 1, response to programmed stimulation was the same after intravenous and oral procainamide administration, with no inducible ventricular arrhythmia in 5 of 15 patients. In group 2, 3 of 18 patients had no inducible arrhythmia after intravenous compared with 7 of 18 patients after oral procainamide administration. There was a different response to programmed stimulation after oral compared with intravenous procainamide in 6 of 18 patients in group 2 but in none of 15 patients in group 1 (p = 0.02). The effective procainamide concentration was greater than the ineffective concentration in five of the six patients with a discordant response, and the effective route of administration was oral in five of the six patients. The change in ventricular refractoriness in group 1 was similar after intravenous (28 +/- 23 ms) and oral (29 +/- 19 ms) procainamide, whereas in group 2, refractoriness was increased more after oral (33 +/- 21 ms) than intravenous (20 +/- 17 ms) procainamide administration and paralleled the difference in procainamide concentration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of combined use of intravenous salbutamol and aminophylline on cardiac rhythm in chronic obstructive lung disease

The effect on cardiac rhythm of intravenous administration of salbutamol during prolonged aminophylline infusion was evaluated by means of ECG Holter monitoring in 20 patients with chronic obstructive lung disease (COLD) without respiratory failure. Data were compared with a baseline 24-hour Holter monitoring during which an individual arrhythmia pattern was established for each patient. Intravenous administration of aminophylline with fast achievement of therapeutic plasma levels, has a variable and nonsignificant influence on supraventricular arrhythmias, whilst a statistically significant increase of premature ventricular contractions (PVCs) has been observed. However, such an increase concerns only isolated PVCs, is conditioned by the pattern of preexisting arrhythmias and is independent of plasma aminophylline level. Acute intravenous administration of salbutamol during infusion of aminophylline is not associated with a higher incidence of major arrhythmias. So we conclude that such a pharmacological combination does not represent an additional risk of serious cardiac rhythm disturbances in a selected population of COLD patients without further known arrhythmogenic risk factors. Moreover, plasma aminophylline levels are not predictive of a possible higher incidence of ventricular arrhythmias.     

Prostaglandin modulation of early afterdepolarizations and ventricular tachyarrhythmias induced by cesium chloride combined with efferent cardiac sympathetic stimulation in dogs

Prostaglandins inhibit efferent cardiac sympathetic nerve effects by acting at presynaptic sites and may act to suppress some arrhythmias. In the present study, the effects of intravenous administration of prostacyclin (PGI2) and prostaglandin E2 (PGE2) on early afterdepolarizations and ventricular tachycardia induced by cesium chloride (0.5 mmol/liter per kg body weight intravenously) combined with stimulation of bilateral ansae subclaviae in anesthetized dogs were examined. The right atrium was paced at a constant cycle length of 600 ms. A left ventricular endocardial monophasic action potential catheter was used to detect early afterdepolarizations. Prostacyclin (0.2 microgram/kg per min) reduced the amplitude of the early afterdepolarizations (39.2 +/- 8.4% of the monophasic action potential amplitude during control study to 28.7 +/- 5.5%, n = 10; p less than 0.001) as well as the prevalence of ventricular tachycardia (11 of 14 dogs during control study to 5 of 14 dogs; p = 0.031). Prostaglandin E2 (0.2 to 0.6 microgram/kg per min) did not significantly reduce the early afterdepolarization amplitude (34.7 +/- 8.9% to 25.1 +/- 10.7%, n = 8; p = 0.085) or the prevalence of ventricular tachycardia (8 of 10 versus 6 of 10 dogs; p = 0.50). Alpha- and beta-adrenoceptor blockade with combined intravenous administration of propranolol (0.5 mg/kg) and phentolamine (0.3 mg/kg) decreased the amplitude of the early afterdepolarizations induced by cesium chloride and bilateral ansae subclaviae stimulation from 38.6 +/- 11.2% to 18.8 +/- 3.3% (n = 6; p = 0.005). Additional administration of PGI2 further reduced the early afterdepolarization amplitude from 18.8 +/- 3.3% to 9.8 +/- 4.8% (n = 6; p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of repeated sauna treatment on ventricular arrhythmias in patients with chronic heart failure.

BACKGROUND: The aim of the present study was to determine whether repeated 60 degrees C sauna treatment improves cardiac arrhythmias in chronic heart failure (CHF) patients, because ventricular arrhythmias are an important therapeutic target in CHF. METHODS AND RESULTS: Thirty patients (59+/-3 years) with New York Heart Association functional class II or III CHF and at least 200 premature ventricular contractions (PVCs)/24 h assessed by 24-h Holter recordings were studied. They were randomized into sauna-treated (n=20) or non-treated (n=10) groups. The sauna-treated group underwent a 2-week program of a daily 60 degrees C far infrared-ray dry sauna for 15 min, followed by 30 min bed rest with blankets, for 5 days per week. Patients in the non-treated group had bed rest in a temperature-controlled room (24 degrees C) for 45 min. The total numbers of PVCs/24 h in the sauna-treated group decreased compared with the non-treated group [848+/-415 vs 3,097+/-1,033/24 h, p<0.01]. Heart rate variability (SDNN, standard deviation of normal-to-normal beat interval) increased [142+/-10 (n=16) vs 112+/-11 ms (n=8), p<0.05] and plasma brain natriuretic peptide concentrations decreased [229+/-54 vs 419+/-110 pg/ml, p<0.05] in the sauna-treated group compared with the non-treated group. CONCLUSION: Repeated sauna treatment improves ventricular arrhythmias in patients with CHF.     

Clinical study on benefit and safety of frequent inhalation of aerosolized procaterol hydrochloride in aged acute asthmatics]

We studied the hemodynamic effects of frequent inhalation of aerosolized procaterol hydrochloride (PRC) in the treatment of status asthmaticus. Twenty patients were enrolled and divided into 2 groups; younger group (less than 55 years; n = 11) and older group (more than 55 years; n = 9). All patients were treated with intravenous hydrocortisone (4 mg/kg/4 h) and PRC inhalation (30 micrograms; 0.3 ml) every hour via a jet nebulizer with 3 l/min oxygen for four consecutive days. Holter ECG monitoring was performed on the 1st, 4th, and 7th days of hospitalization to evaluate mean heart rate, tachycardiac incidence, and arrhythmias. Blood pressure, serum potassium levels, and peak expiratory flow rate (PEFR) were measured on the same day. Even though the total dosage of inhaled PRC on the 1st day was 496.4 +/- 62.61 micrograms for the younger group and 490.0 +/- 36.73 micrograms for the older group (p = NS), total arrhythmic ratios were less than 1% in both group. Both blood pressure and heart rate decreased with improvement of symptoms and PEFR value. Serum potassium levels tended to decline according to the administered dosage of PRC (p < 0.01); however, severe hypokalemia less than 3.0 mmol/l was not observed. We conclude that frequent inhalation of PRC (up to 500 micrograms/day) via a jet nebulizer provides rapid relief from acute asthmatic attacks, and is safe clinically even in aged asthmatics receiving intravenous steroids.     

The signal-averaged electrocardiogram and ventricular arrhythmias after thrombolysis for acute myocardial infarction

The prevalence of an abnormal signal-averaged electrocardiogram (ECG) and ventricular arrhythmias on 24 h ambulatory electrocardiography was evaluated in 118 patients 13 +/- 2 days after acute myocardial infarction. Group 1 (46 patients) underwent intravenous thrombolysis within 6 h of the onset of symptoms, whereas Group 2 (72 patients) did not. An abnormal signal-averaged ECG was seen in 15% of patients in Group 1 and 21% of those in Group 2 (difference not significant). The number of ventricular premature complexes/h was lower in Group 1 than in Group 2: 2.58 +/- 1.63 versus 7.91 +/- 10.75 (p less than 0.01). However, complex arrhythmias (greater than or equal to 10 ventricular premature complexes/h or ventricular tachycardia) were equally common in Groups 1 and 2 (20% versus 22%, respectively). Their prevalence was similar in patients with or without an abnormal signal-averaged ECG (29% versus 18%, respectively, in Group 1 and 27% versus 21%, respectively, in Group 2). Comparison between patients with (n = 26) or without (n = 20) angiographic patency of the infarct-related coronary artery after thrombolysis showed no significant difference in the prevalence of an abnormal signal-averaged ECG (8% versus 25%, respectively) and complex ventricular arrhythmias (19% versus 20%, respectively). These data suggest that thrombolysis does not affect the prevalence of complex ventricular arrhythmias and an abnormal signal-averaged ECG or their relation after acute myocardial infarction.     

Prevention of life-threatening arrhythmias by pharmacologic stimulation of the muscarinic receptors with oxotremorine.

The potential antiarrhythmic efficacy of pharmacologic parasympathetic activation is still controversial. This study assessed the antiarrhythmic effect of saline solution (n = 9) and of the muscarinic agonist oxotremorine (1.5 micrograms/kg administered intravenously) (n = 17) in a feline animal model in which malignant arrhythmias were reproducibly elicited by the combination of acute myocardial ischemia and left stellate ganglion stimulation. Although saline solution had no effect, oxotremorine significantly decreased heart rate, blood pressure, the incidence of ventricular fibrillation from 47% to 0% (p = 0.004), and the incidence of malignant arrhythmias (either ventricular tachycardia or ventricular fibrillation) from 88% to 12% (p less than 0.001). When reduction in heart rate was prevented by means of atrial pacing (n = 15), the incidence of malignant arrhythmias was still significantly reduced from 87% to 27% (p = 0.001). Arrhythmias were also graded as follows: 0 = no premature ventricular contractions; 1 = 1 to 10 premature ventricular contractions; 2 = 11 to 50 premature ventricular contractions; 3 = ventricular tachycardia; 4 = ventricular fibrillation. Arrhythmia severity was 3.29 +/- 0.16 (SEM) in the control trials and was reduced to 0.76 +/- 0.26 (p less than 0.001) by oxotremorine and to 1.53 +/- 0.34 by oxotremorine and pacing (p = 0.002). Therefore a muscarinic agonist can significantly reduce malignant arrhythmias during acute myocardial ischemia and may represent a novel approach to the prevention of sudden cardiac death.     

Amiodarone therapy: role of early and late electrophysiologic studies

Forty-two patients with a history of symptomatic ventricular tachycardia or cardiac arrest underwent electrophysiologic testing at control and early in the course of amiodarone therapy (mean 12 +/- 7 days). Late electrophysiologic studies (mean 17 +/- 4 weeks) were repeated in 23 patients on a maintenance dose of 400 mg/day. At control study, all patients had inducible ventricular tachyarrhythmias (sustained ventricular tachycardia in 35, nonsustained ventricular tachycardia in 4, ventricular fibrillation in 3), while after amiodarone loading (1,200 mg daily) 4 (10.5%) of the 42 patients developed noninducible ventricular arrhythmias. At late study, an additional 6 (26%) of the 23 patients with inducible arrhythmias at early study developed noninducible arrhythmias. The cycle length of induced ventricular tachycardia increased from 275 +/- 61 ms at control study to 340 +/- 58 ms at early study (p = 0.001). A further increase in ventricular tachycardia cycle length was noted in patients who underwent both early and late study (341 +/- 38 versus 375 +/- 63 ms, p less than 0.05). The percent of induced tachycardias that were clinically tolerated increased as patients were treated longer with amiodarone (control = 22%, early = 34%, late = 53%, p less than 0.001). Of the 23 patients who had both early and late electrophysiologic studies and were followed up for a mean of 21.7 months (range 4 to 47), there were no recurrences among the 6 patients with noninducible arrhythmias, but there were five recurrences among the 17 patients with persistently inducible arrhythmias. None of the four patients with noninducible arrhythmias at early study had a recurrence. On the basis of these findings, it is concluded that: 1) The timing of programmed electrical stimulation will affect the results of the study in patients treated with oral amiodarone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrophysiologic and antiarrhythmic effects of sotalol in patients with life-threatening ventricular tachyarrhythmias

Sotalol is a unique beta-blocker that lengthens cardiac repolarization and effective refractory period (ERP). Its efficacy after intravenous (1.5 mg/kg) and oral (160 to 480 mg bid) administration was therefore evaluated in 37 patients with refractory recurrent ventricular tachycardia/fibrillation (VT/VF). Thirty-five patients, 33 with inducible VT/VF, underwent electrophysiologic testing. Intravenous sotalol lengthened the ERP in the atrium (+24.6%, p less than .01), atrioventricular node (+24.9%, p less than .01), and ventricle (+14.9%, p less than .01). It also significantly lengthened sinus node recovery time, corrected QT interval (QTc), and the AH interval, but not the HV interval. Sotalol prevented reinduction of VT/VF in 15 patients (45.5%). Twenty-five of the 33 patients (15 with positive results of electrophysiologic tests; 10 with negative results) were given oral sotalol. The drug was ineffective in seven (26.9%) and aggravated arrhythmia in one (3.8%). In four patients sotalol was withdrawn because of side effects; arrhythmias recurred late in two (7.7%). Eleven patients (42.3%) have continued on oral sotalol over a mean follow-up period of 9.2 +/- 8.6 months. Sotalol reduced (n = 21) total premature ventricular complex (PVC) count on the Holter electrocardiogram by 73% (p less than .01), paired PVCs by 89% (p less than .01), and beats of ventricular tachycardia by 95% (p less than .01). In 52% (n = 11), total reduction in PVCs was at least 85%, and incidence of paired and tachycardiac beats was reduced at least 90% (group A). In the remainder (n = 10), PVC suppression was not significant (group B). Group A included nine patients with nonreinducible VT/VF and two in whom it was reinducible; in group B, eight of 10 patients had reinducible VT/VF. The difference between the two groups (Fisher exact test) was significant (p less than .01). The prevention of reinduction of VT/VF by intravenous sotalol and suppression of spontaneously occurring arrhythmias by the oral drug were both predictive of long-term drug efficacy. Sotalol is a significant advance in the short- and long-term management of life-threatening ventricular tachyarrhythmias.     

Acute effects of intravenous propafenone on the internal ventricular defibrillation threshold in the anesthetized dog

In 10 treated and 2 control dogs, the short-term effects of intravenous propafenone (2 mg/kg/10 minutes, followed by 1 mg/min [n = 2] or 25 micrograms/kg/min [n = 8]) on the internal ventricular defibrillation energy requirements (DER) were investigated. Multiple stored energy levels were randomly tested and the percent successful defibrillation was plotted against the stored energy, and the raw data were fit by logistic regression. The energy at 50% (E50) and 80% (E80) defibrillation success increased after propafenone by a mean of 75% (8.4 +/- 2.4 to 14.7 +/- 5.9 joules, p less than or equal to 0.05) and 59% (11.1 +/- 3.5 to 17.6 +/- 6.7 joules, p less than or equal to 0.05), respectively. Plasma propafenone levels ranged from 778 to 2554 ng/ml (1495 +/- 592 ng/ml) at the beginning to 833 to 2193 ng/ml (1297 +/- 389 ng/ml) at the end of the defibrillation trials. Two dogs served as controls and received Ringer's solution instead of propafenone and showed the temporal stability of the preparation. In conclusion, intravenous propafenone increases the internal ventricular DER in this canine model. This may have important clinical implications in patients with automatic implantable cardioverter-defibrillators (AICDs) receiving concomitant antiarrhythmic drug therapy and in patients undergoing therapy with intravenous propafenone.     

Randomized double-blind study of intravenous tocainide versus lidocaine for suppression of ventricular arrhythmias after cardiac surgery

To compare the therapeutic efficacy and safety of intravenous tocainide with that of intravenous lidocaine in patients with ventricular arrhythmias after cardiac surgery, 25 patients were randomized to either agent in a double-blind manner. Tocainide was given in 16 patients as a 250 mg bolus followed by a loading infusion of 500 mg over 15 minutes and a maintenance infusion of 33.3 mg/min. Lidocaine was administered in 9 patients as a 100 mg bolus followed by a loading infusion of 60 mg over 15 minutes and a maintenance infusion of 1.4 mg/min. Therapy was continued for 24 hours in initially responding patients. With analysis of 24-h taped electrocardiograms it was found that single premature ventricular complexes (PVCs) were suppressed by tocainide by more than 80% in 94% of patients and by lidocaine in 75% of patients (p = NS). Couplets and ventricular tachycardia events were eliminated in all patients by either drug. Multiform PVCs were abolished in 94% of the patients after tocainide and in 75% after lidocaine (p = NS). Average overall success over the 24 hours with more than 80% suppression of single PVCs and simultaneous elimination of higher forms of arrhythmia was 71% with tocainide and 59% with lidocaine (p = NS). Adverse effects were negligible, with only one patient in the lidocaine group developing diaphoresis without necessitating termination of therapy. Treatment rapidly produced and then maintained blood levels of 4-10 mg/l for tocainide and 1-4 mg/l for lidocaine. We conclude that intravenous tocainide is well tolerated and has comparable efficacy to lidocaine in the acute therapy of postcardiac surgery ventricular arrhythmias.     

Arrhythmogenic effects of orally administered bronchodilators.

The respiratory and circulatory effects of orally administered ephedrine sulfate, 25 mg, aminophylline, 400 mg, terbutaline sulfate, 5 mg, and placebo were evaluated in 20 patients with ventricular arrhythmia by a double-blind crossover method. The bronchodilator effect of terbutaline was similar to that of aminophylline over four hours but superior to ephedrine at the fourth hour. Both terbutaline and ephedrine exhibited chronotropic effects, with the effect of terbutaline greater than that of ephedrine at the fourth hour. The effect of aminophylline on heart rate did not differ from placebo. Only terbutaline was associated with an increase in ventricular ectopic beats. Ventricular tachycardia occurred in three patients treated with terbutaline and in one patient with ephedrine. There were no significant changes in blood pressure. Orally administered terbutaline should not be regarded as safer than orally administered ephedrine or aminophylline in patients with arrhythmias.