Reduction In Ventricular Premature Beats Research Articles

The incidence of cardiac arrhythmias during exercise stress testing: a focus on patients with severe obesity undergoing sleeve gastrectomy.

Obesity is associated with a higher risk of cardiac arrhythmias. Sleeve gastrectomy (SG) is a common bariatric surgery with beneficial effects on weight loss and comorbidities. The study aimed to investigate the prevalence of arrhythmias during maximal exercise testing in patients with moderate-severe obesity and to evaluate the impact of SG on these arrhythmic events. All patients with moderate or severe obesity who were considered suitable candidates for SG between June 2015 and September 2020 were recruited. Each patient underwent three incremental, maximal, ECG-monitored cardiopulmonary exercise test 1 month before and 6 and 12 months after SG; the frequency and complexity of ventricular premature beats (VPBs) and atrial premature beats (APBs) have been evaluated during rest, exercise and recovery phases. Fifty patients with severe obesity (BMI 46.39 ± 7.89 kg/m2) were included in the study. After SG, patients presented a decreased BMI (34.15 ± 6.25 kg/m2 at 6 months post-SG and 31.87 ± 5.99 kg/m2 at 12 months post-SG). At 6 months post-SG, an increase in VPBs, mainly during the recovery phase, was observed. At 12 months post-SG, a reduction in VPBs compared with the 6 months evaluation was showed. Although in the early post-surgical phase the risk of exercise-induced arrhythmias may be higher, SG does not seem to increase the occurrence of arrhythmias in the long-term. No life-threating arrhythmias were found during post-SG evaluations.

Amiodarone for arrhythmia in patients with Chagas disease: A systematic review and individual patient data meta-analysis.

BackgroundChagas disease is a neglected chronic condition caused by Trypanosoma cruzi, with high prevalence and burden in Latin America. Ventricular arrhythmias are common in patients with Chagas cardiomyopathy, and amiodarone has been widely used for this purpose. The aim of our study was to assess the effect of amiodarone in patients with Chagas cardiomyopathy.MethodologyWe searched MEDLINE, Embase and LILACS up to January 2018. Data from randomized and observational studies evaluating amiodarone use in Chagas cardiomyopathy were included. Two reviewers selected the studies, extracted data and assessed risk of bias. Overall quality of evidence was accessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE).Principal findingsWe included 9 studies (3 before-after studies, 5 case series and 1 randomized controlled trial). Two studies with a total of 38 patients had the full dataset, allowing individual patient data (IPD) analysis. In 24-hour Holter, amiodarone reduced the number of ventricular tachycardia episodes in 99.9% (95%CI 99.8%-100%), ventricular premature beats in 93.1% (95%CI 82%-97.4%) and the incidence of ventricular couplets in 79% (RR 0.21, 95%CI 0.11–0.39). Studies not included in the IPD analysis showed a reduction of ventricular premature beats (5 studies), ventricular tachycardia (6 studies) and ventricular couplets (1 study). We pooled the incidence of adverse side effects with random effects meta-analysis; amiodarone was associated with corneal microdeposits (61.1%, 95%CI 19.0–91.3, 5 studies), gastrointestinal events (16.1%, 95%CI 6.61–34.2, 3 studies), sinus bradycardia (12.7%, 95%CI 3.71–35.5, 6 studies), dermatological events (10.6%, 95%CI 4.77–21.9, 3 studies) and drug discontinuation (7.68%, 95%CI 4.17–13.7, 5 studies). Quality of evidence ranged from moderate to very low.ConclusionsAmiodarone is effective in reducing ventricular arrhythmias, but there is no evidence for hard endpoints (sudden death, hospitalization). Although our findings support the use of amiodarone, it is important to balance the potential benefits and harms at the individual level for decision-making.

Parathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidism, as evaluated by exercise test

To investigate whether parathyroidectomy (PTx) reverses risk factors for arrhythmias related to the QT dynamic changes evaluated during bicycle ergometry exercise test (ET). Twenty-four postmenopausal women with primary hyperparathyroidism (PHPT) (mean age 60.08.4 years) and 30 sex- and age-matched controls underwent ET, echocardiography, and biochemical evaluation. The following stages were considered during ET: rest, peak exercise, and recovery. The patients were randomized to two groups: 12 underwent PTx (group A) and 12 were followed-up conservatively (group B). After 6 months, the patients were studied again. Groups A and B showed no differences in mean baseline biochemical values, echocardiographic parameters, and QTC interval. PHPT patients showed an increased occurrence of ventricular premature beats (VPBS) during ET compared with controls (37.0 vs 6.6%, P=0.03). Serum calcium level was a predictor of VPBS (P=0.05). Mean value of QTC was in the normal range at baseline (Group A: 401±16.9; group B: 402.25±13.5 ms) but significantly lower than controls (417.8±25.1 ms, P<0.01). A negative correlation was found between QTc and calcium values (P=0.03). Physiological reduction of QTc interval from rest to peak exercise was not observed in PHPT patients before surgery. After PTx, group A had a significant reduction in VPBs compared with baseline (at baseline, 5 of 12 vs none of 12 patients after PTx, P=0.03) and a restored normal QT adaptation during ET. Group B showed no significant changes after a 6-month period. PTx reduces the occurrence of VPBs and restored the QTc adaptation during ET.

Letter Regarding Article by Korte et al, “Female Mice Lacking Estrogen Receptor β Display Prolonged Ventricular Repolarization and Reduced Ventricular Automaticity After Myocardial Infarction”

To the Editor: The article by Korte et al1 was insightful in that it provided evidence that female mice with chronic left anterior myocardial infarction (MI) and lacking estrogen receptor β (ERβ) have prolonged ventricular repolarization compared with noninfarcted ERβ-deficient and wild-type mice. The prolongation of ventricular repolarization in the ERβ-deficient mice with MI was demonstrated by the prolonged QT and QTc interval with an associated reduction of the expression of Kv4.3 channel (coding for I to). The authors surmised that the observed reduction in ventricular premature beats (VPB) and nonsustained runs of VPB in ERβ-deficient mice with MI …

Attenuation of the antiarrhythmic effects of ischaemic preconditioning by blockade of bradykinin B2 receptors.

1. The possibility that bradykinin is involved in the pronounced antiarrhythmic effects of ischaemic preconditioning in anaesthetized mongrel dogs was examined with the use of the selective B2 antagonist, icatibant (Hoe-140). 2. Preconditioning, achieved by two 5 min occlusions of the left anterior descending coronary artery, followed 20 min later by a 25 min occlusion of the same artery resulted, during this prolonged occlusion, in less severe arrhythmias (VF 0% versus 47% in control non-preconditioned dogs), reductions in the incidence and number of episodes of ventricular tachycardia (VT) and in the number of ventricular premature beats and increased survival following reperfusion (50% versus 0% in the controls). 3. Hoe-140 was given in a dose of 300 micrograms kg-1 either before the preconditioning procedure or after preconditioning but before the prolonged occlusion. This dose of Hoe-140 had insignificant haemodynamic effects and failed to modify the increase in coronary blood flow that occurred in the circumflex coronary artery when the anterior descending branch was occluded. 4. It was difficult to precondition dogs in the presence of Hoe-140. There were more ventricular arrhythmias during the initial 5 min occlusion (44 +/- 12 versus 10 +/- 3) and a higher incidence of ventricular fibrillation (50% versus 21%) during the preconditioning procedure. There was also a more pronounced ST-elevation (recorded from epicardial electrodes) during the preconditioning occlusions in those dogs given Hoe-140. 5. In those dogs that survived to the long (25 min) occlusion, Hoe-140 prevented the antiarrhythmic effects of preconditioning (reduction in ventricular premature beats and in VT) although all the dogs survived the occlusion period. However on reperfusion, survival in the preconditioned dogs given Hoe-140 was less than in those dogs preconditioned without the B2 antagonist.6. Changes in the degree of inhomogeneity of conduction within the ischaemic area, which were markedly suppressed by preconditioning, were attenuated in those dogs preconditioned in the presence of Hoe-140.7. These results suggest that bradykinin acts as both a 'trigger' for preconditioning and as one of the mediator protective (antiarrhythmic) substances generated by the myocardium under these conditions.Since the protection afforded both by preconditioning and by local intracoronary infusions of bradykinin is markedly attenuated by an inhibitor of the L-arginine nitric oxide pathway, we suggest that much of the protection afforded by ischaemic preconditioning results from the generation of nitricoxide, and that bradykinin, released early during ischaemia, acts as a stimulant for this generation.

Hoe 694, a new Na+/H+ exchange inhibitor and its effects in cardiac ischaemia.

1. The benzoylguanidine derivative Hoe 694 ((3-methylsulphonyl-4- piperidino-benzoyl) guanidine methanesulphonate) was characterized as an inhibitor of Na+/H+ exchange in rabbit erythrocytes, rat platelets and bovine endothelial cells. The potency of the compound was slightly lower or comparable to ethylisopropyl amiloride (EIPA). 2. To investigate a possible cardioprotective role of the Na+/H+ exchange inhibitor Hoe 694, rat isolated working hearts were subjected to ischaemia and reperfusion. In these experiments all untreated hearts suffered ventricular fibrillation on reperfusion. Addition of 10(-7) M Hoe 694 to the perfusate almost abolished reperfusion arrhythmias in the rat isolated working hearts. 3. Hoe 694 reduced the release of lactate dehydrogenase (LDH) and creatine kinase (CK), which are indicators of cellular damage during ischaemia, into the venous effluent of the hearts by 60% and 54%, respectively. 4. The tissue content of glycogen at the end of the experiments was increased by 60% and the high energy phosphates ATP and creatine phosphate were increased by 240% and 270% respectively in the treated hearts as compared to control hearts. 5. Antiischaemic effects of the Na+/H+ exchange inhibitor, Hoe 694, were investigated in a second experiment in anaesthetized rats undergoing coronary artery ligation. In these animals, pretreatment with Hoe 694 caused a dose-dependent reduction of ventricular premature beats and ventricular tachycardia as well as a complete suppression of ventricular fibrillation down to doses of 0.1 mg kg-1, i.v. Blood pressure and heart rate remained unchanged. 6. We conclude that the new Na+/H+ exchange inhibitor, Hoe 694, shows cardioprotective and antiarrhythmic effects in ischaemia and reperfusion in rat isolated hearts and in anaesthetized rats. In view of the role which Na+/H+ exchange seems to play in the pathophysiology of cardiac ischaemia these effects could probably be attributed to Na+/H+ exchange inhibition.

Effects of Na +/H + exchange inhibitors in cardiac ischemia

To investigate a possible protective role of Na +/H + exchange inhibition under ischemic conditions isolated rat hearts were subjected to regional ischemia and reperfusion. In these experiments all 6 untreated hearts suffered ventricular fibrillation on reperfusion. Addition of 1 × 10 −5 mol/l amiloride or 3 × 10 −7 mol/l 5-( N-ethyl- N-isopropyl)amiloride (EIPA) markedly decreased the incidence and duration of ventricular fibrillation or even suppressed fibrillation completely as in the case of 1 × 10 −6 mol/l EIPA. Both compounds diminished the activities of lactate dehydrogenase and creatine kinase in the venous effluent of the hearts during ischemia. At the end of the experiments tissue contents of glycogen, ATP and creatine phosphate were increased in the treated hearts as compared to control hearts. In an additional experiment the beneficial effects of Na +/H + exchange inhibition during ischemia was confirmed in vivo with anaesthetized rats undergoing coronary artery ligation. In these animals amiloride or EIPA pretreatment caused a marked reduction of ventricular premature beats and ventricular tachycardia as well as a complete suppression of ventricular fibrillation. The concentration dependent inhibition of Na + influx via Na +/H + exchange by amiloride and EIPA was investigated in erythrocytes from hypercholesterolemic rabbits with Na +/H + exchange activated by exposure to hyperosmotic medium. Furthermore the inhibition of Na + influx by EIPA after intracellular acidification was studied in cardiac myocytes of neonatal rats. Both agents were effective in the same order of potency in the ischemic isolated working rat heart as in the erythrocyte model in which they inhibited Na +/H + exchange. In addition the anti-ischemic effects of EIPA were seen over the same concentration range over which the compound inhibited Na +/H + exchange in acidified cardiac myocytes. This indicates that the anti-ischemic actions and the effects observed in erythrocytes or cardiac cells might be caused by a common mechanism. We suggest that amiloride and EIPA show cardioprotective and antiarrhythmic effects in ischemia and reperfusion which could probably be attributed to Na +/H + exchange inhibition.

Combination of Antiarrhythmic Drugs

Antiarrhythmic treatment with single agents is often ineffective and can be limited by dose-dependent side effects. Therefore, combinations of antiarrhythmic drugs in smaller and well-tolerated doses are advocated in cases refractory to single antiarrhythmic drugs. Basically, substances belonging to the same electrophysiologic class should not be combined. However, drugs of different subsets of class I may be combined. Agents that have pharmacokinetic interactions, such as quinidine and amiodarone, should not be given together because this combination may be associated with a considerable proarrhythmic effect. A combination of beta-adrenoreceptor blockers with class I antiarrhythmic drugs may be effective, mainly in cases in which the arrhythmia is dependent on adrenergic stimulation. The combination of class III and IB substances can be useful in some cases, from the electrophysiological and clinical point of view. Among the successful combinations of this type are amiodarone and mexiletine, sotalol and mexiletine, or sotalol and tocainide. In 34 patients, the reduction of ventricular premature beats by sotalol alone was 28%, and by sotalol plus mexiletine or tocainide was 79%. Complex ventricular arrhythmias were suppressed by sotalol alone by less than 40% and by sotalol plus mexiletine or tocainide by more than 80%. There was no difference in the effectiveness of mexiletine and tocainide (both of them being class IB drugs) in this combination. However, mexiletine was associated with fewer adverse effects than was tocainide. In patients refractory to amiodarone alone or to a combination with mexiletine, the combined treatment with amiodarone and class IC drugs such as flecainide and encainide prolongs the cycle length of ventricular tachycardia, but does not suppress induction of ventricular tachycardia during programmed stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Antiarrhythmic effects of a benzothiazine derivative (SD-3211) and its stereoisomer (SA3212) in anaesthetized rats and isolated perfused rat hearts compared with bepridil

The antiarrhythmic effects of a new calcium channel blocking agent (SD-3211) and its stereoisomer with additional sodium channel blocking activity (SA3212), were compared with those of a known antiarrhythmic drug (bepridil), using the left coronary artery ligation- and reperfusion-associated arrhythmia models both in isolated rat hearts and in anaesthetized rats. Isolated and perfused rat hearts were subjected to regional ischaemia for 15 min and subsequent reperfusion for 5 min. SD-3211 and SA3212 showed dose-dependently prolongations of the time interval between coronary ligation and first appearance of ventricular premature beats, reductions in the number of total ventricular premature beats during the ligation period and reductions in the incidence of reperfusion-induced ventricular fibrillation. The values of the negative logarithm of IC50 (mol/l) of SD-3211, SA3212 and bepridil were 7.97, 7.41 and 6.64 for the reduction of ventricular premature beats during ligation and 6.43, 7.49 and 6.17 for the reduction of ventricular fibrillation during reperfusion, respectively. In a separate study on force of concentration and coronary flow in perfused heart paced at 340-360 beats/min SD-3211 caused a significant negative inotropic effect between 10(-7) and 10(-6) mol/l. SA3212 at the concentration of less than 10(-6) mol/l did not result in any significant change in force of contraction. The coronary flow was increased dose-dependently by SA3212, while it was first increased and then reduced in the presence of higher concentration of SD-3211 (greater than 10(-7) mol/l). Hearts of anesthetized rats were also subjected to regional ischaemia for 7 min and subsequent reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous lorcainide for symptomatic ventricular tachyarrhythmias: Comparison with lidocaine and oral lorcainide

Intravenous lorcainide and lidocaine were administered to 25 patients with symptomatic ventricular tachyarrhythmias in a randomized single-blind crossover study. Prior to drug therapy, each patient underwent 48 hours of ambulatory monitoring and exercise testing on a motorized treadmill. At the completion of baseline studies, patients were randomized to receive either lidocaine or lorcainide intravenously. The dose of lidocaine was 1.0 mg/kg by bolus followed by an infusion of 2 to 3 mg/min. The dose of lorcainide was 2.0 mg/kg followed by a constant infusion of 200 to 300 mg over 24 hours. Two patients developed side effects on lidocaine and the infusion was discontinued prior to evaluation of efficacy. Of the remaining 23 patients, 11 (48%) had their arrhythmia controlled, defined as a >90% reduction in repetitive forms (couplets and ventricular tachycardia) and a 50% reduction in ventricular premature beats. Lorcainide was effective in 8 of the 25 patients (32%). There was no correlation between the effect of lidocaine and the response to lorcainide ( p = NS). Oral lorcainide therapy was administered to 17 patients who were free of side effects during the intravenous infusion. The oral drug was effective in nine patients (53%), five of whom had responded to the intravenous drug, and was ineffective in eight, seven of whom were also unresponsive to intravenous lorcainide. The intravenous drug predicted the response to the oral form in 71% of patients, but this was not statistically significant. Side effects occurred in 10 patients (59%) and were primarily neurologic. In conclusion, intravenous lidocaine and lorcainide are equally effective for suppressing ventricular arrhythmias, but 30% of patients will respond to only one of these agents. Oral lorcainide is an effective agent for long-term therapy, but its effect is not reliably predicted by the response to the intravenous preparation, as 30% of patients have discordant responses. Side effects from lorcainide are frequent and may limit its usefulness.

The renin-angiotensin system and treatment of heart failure

From the Heart and Hypertension Department, Research Institute of the Cleveland Clinic Foundation, Cleveland, Ohio. Requests for reprints should be addressed to Dr. Fetnat M. Fouad-Taraii, Heart and Hypertension Department, Research Institute of the Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44106. It has been years since converting enzyme inhibitors were introduced for the treatment of congestive heart failure. Their effectiveness has been demonstrated in multiple reports that have shown improvement in hemodynamic indexes as well as clinical symptoms and quality of life [l-IO]. Moreover, this improvement generally lasted months or years. Our experience in this respect is summarized in Table I. We have studied 14 patients with congestive heart failure of ischemic or cardiomyopathic etiology, before and after captopril therapy, and obtained hemodynamic data at regular intervals over one year. These studies showed that cardiac output and stroke volume increased significantly in association with normalization of pulmonary mean transit time, reduction of plasma aldosterone, and some reduction in both plasma catecholamine levels and heart rate. These effects occurred within one week and were sustained. Changes in ejection fraction, however, were minimal compared with the significant reduction in mean transit time (Figure 1) probably because ejection fraction depends on left ventricular geometry in addition to loading conditions on the heart. Along with these hemodynamic findings, improvement in severity of heart failure (NYHA class) and its other clinical manifestations has been described in patients treated with converting enzyme inhibitors by Dzau et al [7], Levine et al [8], and others. Goldstein and Pitt [l l] also demonstrated that, compared with placebo and with digoxin, captopril treatment of heart failure resulted in significantly improved exercise duration, a 45 percent reduction of ventricular premature beats, and a reduction in frequency of hospitalization. The mechanism by which converting enzyme inhibitors maintain improvement is still not well understood. Several possibilities include: (1) the persistent beneficial hemodynamic effects of converting enzyme inhibition o’n afterload and preload; (2) persistent suppression of plasma aldosterone; (3) interference with the effects of angiotensin II on the renal tubules; and (4) a direct effect of accumulated angiotensin I on the heart v21. Compared with other vasodilators, captopril has been found to be more effective in improving effort tolerance in association with a more marked reduction in blood pressure and pulmonary mean transit time and a more marked increase in cardiac output [13]. These findings indicated that the hemodynamic changes induced by converting enzyme inhibitors are not the only factors mediating the long-term control of congestive heart failure during therapy. Moreover, tolerance to therapy was observed with other vasodilators but did not develop when captopril was used for a similar duration, suggesting that additional effects of converting enzyme inhibitors should be considered. For example, humoral studies in these pa-

Ethmozine ® (moricizine HCl) therapy for complex ventricular arrhythmias

Moricizine HCl (Ethmozine ®), a new antiarrhythmic agent, was administered to 102 patients with refractory ventricular fibrillation (n = 31), sustained ventricular tachycardia (VT) (n = 46) or symptomatic nonsustained VT (n = 25). A noninvasive approach utilizing monitoring and exercise testing was used in 82 patients who had a high density of reproducible spontaneous arrhythmia, whereas 20 patients without such arrhythmia required invasive electrophysiologic testing. The dosage of moricizine HCl was 200 mg 3 times daily, and during 5 to 6 days was titrated up to a maximum of 400 mg 3 times daily or 15 mg/kg daily, based on arrhythmia suppression and occurrence of side effects. Criteria for efficacy were a > 90% reduction in repetitive ventricular premature beats (couplets and runs of VT) and a > 50% reduction in ventricular premature beats when noninvasive methods were used. When electrophysiologic testing was used, the drug was judged effective if it prevented the induction of > 2 repetitive responses. Of 75 patients completing noninvasive study, 30 (40%) responded to moricizine HCl therapy, whereas only 1 of 20 patients undergoing electrophysiologic testing responded. There was no difference in moricizine HCl blood levels between responders and nonresponders (0.41 μg/ml vs 0.43 μg/ml, difference not significant). Side effects occurred in 28 patients (27%). Most frequent were aggravation of arrhythmia (n = 12), nausea and vomiting (n = 5), central nervous system toxicity (n = 3) and anticholinergic side effects (n = 3). The response rate to moricizine HCl therapy was higher in patients with nonsustained VT (62%) compared with those with sustained VT (19%) or ventricular fibrillation (33%). The response rate was 35% in patients with a left ventricular ejection fraction > 40% and 18% in those with an ejection fraction < 40% (p < 0.05). There was no difference in the density of arrhythmia during baseline studies between responders and nonresponders. Of 23 patients discharged while taking moricizine HCl, 12 patients have continued the drug for a mean follow-up of 17 months. Four patients died suddenly after 24 months, and 4 patients had a nonfatal recurrence after 5 months. Moricizine HCl is a well-tolerated antiarrhythmic drug particularly effective in patients with nonsustained VT and intact left ventricular function.

Intravenous Lorcainide Versus Lidocaine in the Treatment of Frequent and Complex Ventricular Arrhythmias

Abstract Thirty patients with frequent (≥30/hr) and repetitive ventricular premature beats (VPBs) unassociated with acute infarction were randomized to intravenous lorcainide (LOR) or lidocaine (LID). Following at least 2 hours of baseline Holter monitoring, patients received LOR, 2 mg/kg then 200 mg/24hr, or LID, 1 mg/kg then 2 mg/min, with rebolus if needed. Nonresponders detected by bedside telemetry were crossed over. Clinical response was 6 of 25 (24%) including two of nine crossovers with LOR and 8 of 26 (31%) including 3 of 12 crossovers with LID ( p = NS). By computer analysis of 24-hour Holter monitors and asymptotic regression of success rates at hourly intervals, it was projected that ≥80% reduction in VPBs occurred in 28% of LOR and in 25% of LID ( p = NS), and complete suppression of repetitive VPBs occurred in 102% of LOR and in 92% of LID ( p = NS). The mean drug levels were 405 ng/ml (range 371 to 463) with LOR and 3.4 μg/ml (range 2.1 to 3.6) with LID. Side effects were similar, occurring in 8 of 25 LOR trials and in 11 of 26 LID trials ( p = NS). Thus, LOR and LID effectively suppress repetitive VPBs and to a lesser extent VPB frequency. However, neither drug is superior and each may be an effective alternative when resistance to the other is encountered.

Arrhythmia control and other factors related to sudden death in coronary disease patients at intermediate risk

Thirty-three patients with coronary artery disease and frequent, complex ventricular arrhythmias (VA) were followed long-term to evaluate factors related to sudden death (SD). Patients with malignant VA (sustained ventricular tachycardia (VT), resuscitated SD, or acute myocardial infarction) were excluded. Baseline data included angiographic ejection fraction (EF), segmental wall motion, and Holter evidence of frequent (>30/hr) and complex (repetitive) ventricular premature beats (VPBs). Control of VA was attempted with conventional or experimental agents and was defined as ≥70% reduction in VPBs, ≥90% reduction in couplets, and abolition of nonsustained VT on two consecutive Holter tapes. After 24 ± 15 months of follow-up on the single most effective agent, 18 patients survived while 15 patients died suddenly. There was no difference between these groups with respect to age, sex, or baseline VA. Survivors had a higher EF (51% vs 34%, p < 0.001), fewer dyskinetic segments (0.05 vs 1.0, p < 0.01), and better VA control (83% vs 40%, p < 0.01) than nonsurvivors. By analysis of variance, VA control was not independent of EF ( F = 6.98, p < 0.01). The 1-, 2-, and 3-year survival rates were 90%, 90%, and 82% for patients with EF ≥ 40% and 22%, 11%, and 11% for those with EF < 40% and uncontrolled VA. We conclude that left ventricular function and VA control are dependent determinants of sudden death, and this “intermediate” risk group consists of (1) low risk patients with EF ≥ 40% in whom a multicenter placebo-controlled trial may be justified and (2) high risk patients with EF <40% for whom no effective agent can be identified by noninvasive means and in whom a more aggressive approach may be needed.

Intravenous lorcainide versus lidocaine in the treatment of frequent and complex ventricular arrhythmias

Thirty patients with frequent (≥30/hr) and repetitive ventricular premature beats (VPBs) unassociated with acute infarction were randomized to intravenous lorcainide (LOR) or lidocaine (LID). Following at least 2 hours of baseline Holter monitoring, patients received LOR, 2 mg/kg then 200 mg/24hr, or LID, 1 mg/kg then 2 mg/min, with rebolus if needed. Nonresponders detected by bedside telemetry were crossed over. Clinical response was 6 of 25 (24%) including two of nine crossovers with LOR and 8 of 26 (31%) including 3 of 12 crossovers with LID ( p = NS). By computer analysis of 24-hour Holter monitors and asymptotic regression of success rates at hourly intervals, it was projected that ≥80% reduction in VPBs occurred in 28% of LOR and in 25% of LID ( p = NS), and complete suppression of repetitive VPBs occurred in 102% of LOR and in 92% of LID ( p = NS). The mean drug levels were 405 ng/ml (range 371 to 463) with LOR and 3.4 μg/ml (range 2.1 to 3.6) with LID. Side effects were similar, occurring in 8 of 25 LOR trials and in 11 of 26 LID trials ( p = NS). Thus, LOR and LID effectively suppress repetitive VPBs and to a lesser extent VPB frequency. However, neither drug is superior and each may be an effective alternative when resistance to the other is encountered.

Intravenous and oral loading versus oral loading alone with amiodarone for chronic refractory ventricular arrhythmias

To determine whether combined intravenous (i.v.) and oral loading with amiodarone can shorten its onset of action, a comparative study was conducted. Twenty patients with refractory ventricular arrhythmias were treated with amiodarone. All patients had frequent (≥30/hour) and complex (repetitive) ventricular premature beats on a 48-hour baseline Holter recording. Ten patients (group A) received oral loading alone: 800 mg/day for 7 days, 600 mg/day for 3 days, then a maintenance dose 200 to 400 mg/day. Ten patients (group B) received i.v. and oral loading: 5 mg/kg i.v., and then the same regimen as for group A. Follow-up 24-hour Holter recordings were obtained daily for 7 days, weekly for 1 month, and then monthly. Arrhythmia control was defined as at least a 70% reduction in ventricular premature beats, a 90% or greater reduction in couplets and abolition of ventricular tachycardia. The time to optimal ventricular arrhythmia control was shorter for group B (20 ± 18 vs 105 ± 83 days, p < 0.05) and the cumulative amiodarone dose at the time of control was smaller for group B (10 ± 8 vs 48 ± 39 g, p < 0.05). No complications were encountered with i.v. amiodarone. Thus, initial loading with i.v. amiodarone can shorten the time to optimal ventricular arrhythmia control and lower the cumulative dose required.

Comparison of Lorcainide and Quinidine in the Treatment of Ventricular Ectopy

Lorcainide, a new type I antiarrhythmic agent, was compared to quinidine in respect to antiarrhythmic efficacy and clinical safety. Thirteen subjects completed an open, randomized, crossover study with analysis of 24-hour ambulatory ECG monitoring and drug blood levels. The QRS and Q-T intervals increased with both lorcainide and quinidine. The mean reduction in total ventricular premature beats (VPBs) with quinidine was 16 percent compared to 68 percent with lorcainide (p less than .05). With lorcainide eight of 13 subjects had a significant (greater than 82 percent) reduction in VPBs compared to only three of 13 subjects taking quinidine (p less than .05). This same relationship was observed when mean VPB/1,000 heartbeats was analyzed. Ventricular tachycardia was no longer present in five of nine subjects taking lorcainide and in two of nine taking quinidine. No relationship could be established between drug level and arrhythmia suppression in this small population. Some CNS effects were reported in both groups, but no significant hematologic, chemical, or urinary adverse effects were seen with either drug. Thus, lorcainide compares favorably to quinidine in regard to arrhythmia suppression, but was limited in its clinical utility by CNS side effects.

Acute oral testing for determining antiarrhythmic drug efficacy: I. Quinidine

Acute oral drug testing with quinidine was used in 18 patients with high grade ventricular arrhythmia. This method involves administering a single large dose of the antiarrhythmic agent, monitoring heart rhythm by means of programmed trendscription and determining blood drug levels at selected intervals. After quinidine was given in a dose of 0.6 g, 10 patients had a positive response, defined as a 50 percent or greater reduction in ventricular premature beats and abolition of repetitive ectopic beats. Drug action began a mean of 88 minutes after administration, and the mean peak blood quinidine level was 3.2 ± 0.5 (standard error) μg/ml. Four patients had a paradoxic increase in arrhythmia. In nine patients the response to acute drug testing was compared with the response to maintenance quinidine therapy with doses of 1.2 and 1.8 g/day. The presence of arrhythmia was assessed with 24 hour ambulatory monitoring and exercise stress testing. With both techniques, seven of nine patients showed results concordant with those of acute testing. Disparity in results of the two methods of drug administration was explained by the serum concentration of quinidine. Acute oral drug testing provides a new approach for determining expeditiously whether quinidine is effective or hazardous in an individual patient.