Electro-mechanical dysfunction in long QT syndrome: Role for arrhythmogenic risk prediction and modulation by sex and sex hormones.

Long QT syndrome (LQTS) is a congenital arrhythmogenic channelopathy characterized by impaired cardiac repolarization. Increasing evidence supports the notion that LQTS is not purely an "electrical" disease but rather an "electro-mechanical" disease with regionally heterogeneously impaired electrical and mechanical cardiac function. In the first part, this article reviews current knowledge on electro-mechanical (dys)function in LQTS, clinical consequences of the observed electro-mechanical dysfunction, and potential underlying mechanisms. Since several novel imaging techniques - Strain Echocardiography (SE) and Magnetic Resonance Tissue Phase Mapping (TPM) - are applied in clinical and experimental settings to assess the (regional) mechanical function, advantages of these non-invasive techniques and their feasibility in the clinical routine are particularly highlighted. The second part provides novel insights into sex differences and sex hormone effects on electro-mechanical cardiac function in a transgenic LQT2 rabbit model. Here we demonstrate that female LQT2 rabbits exhibit a prolonged time to diastolic peak - as marker for contraction duration and early relaxation - compared to males. Chronic estradiol-treatment enhances these differences in time to diastolic peak even more and additionally increases the risk for ventricular arrhythmia. Importantly, time to diastolic peak is particularly prolonged in rabbits exhibiting ventricular arrhythmia - regardless of hormone treatment - contrasting with a lack of differences in QT duration between symptomatic and asymptomatic LQT2 rabbits. This indicates the potential added value of the assessment of mechanical dysfunction in future risk stratification of LQTS patients.

Effects of amiodarone versus quinidine and verapamil in patients with chronic atrial fibrillation: results of a comparative study and a 2-year follow-up.

Rapid, reliable and safe reestablishment of sinus rhythm is the major aim of pharmacologic treatment in patients with chronic atrial fibrillation. The mainstay of therapy in this arrhythmia has been quinidine. More recently, amiodarone was shown in non-comparative studies to be superior to class IA agents under certain conditions. In 40 patients with atrial fibrillation persisting for 4 weeks up to 2 years, the efficacy and safety of either quinidine and verapamil (days 1 to 3, quinidine 1,500 mg/day; days 4 to 6, quinidine 1,500 mg + verapamil 240 mg/day) or amiodarone therapy (days 1 to 3, amiodarone 1,200 mg/day intravenously; days 4 to 14, amiodarone 800 mg/day orally) were randomly examined. Responders continued on their effective medication for 3 months. Thereafter, all patients were treated with a fixed regimen of quinidine (480 mg/day) plus verapamil (240 mg/day) for up to 2 years. During atrial fibrillation, quinidine reduced mean ventricular cycle length by 40 ms (-5%), quinidine and verapamil increased mean cycle length by 57 ms (8%) and amiodarone by 192 ms (28%, p less than 0.01). In addition, quinidine and verapamil had a characteristic "rate-smoothing" effect on atrioventricular conduction during atrial fibrillation. The rhythm was converted to sinus rhythm after quinidine in 5 (25%) of 20 patients and after the combination of quinidine and verapamil in 11 (55%) of 20 patients. Amiodarone restored sinus rhythm in 12 (60%) of 20 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Ventricular arrhythmias initiated by programmed stimulation in four groups of patients with healed myocardial infarction.

Programmed electrical stimulation of the heart was prospectively used in 160 patients with healed myocardial infarction to study the incidence and characteristics of ventricular arrhythmias induced. Thirty-five patients had neither documented nor suspected ventricular arrhythmias (Group A); 37 patients had documented nonsustained ventricular tachycardia (Group B); 31 patients had been resuscitated from ventricular fibrillation (Group C); and 57 patients had documented sustained monomorphic ventricular tachycardia (Group D). No electrophysiologic differences were found between patients in Group A and Group B, but patients in both groups differed significantly from patients in Group C and Group D. In the last two groups, sustained monomorphic ventricular tachycardia was more frequently induced, the cycle length of the induced ventricular tachycardia was slower and a lesser number of premature stimuli was required for induction. No differences were found in the incidence, rate or mode of induction of nonsustained monomorphic ventricular tachycardia, but nonsustained polymorphic ventricular tachycardia and ventricular fibrillation were more frequently induced in Groups A and B. It is concluded that the substrate for sustained ventricular arrhythmia is present in at least 42% of patients after myocardial infarction. The electrophysiologic characteristics of the substrate for ventricular tachycardia seem to be the major determinant of the clinical occurrence of sustained ventricular arrhythmia. Changes in the electrophysiologic properties of the substrate of ventricular tachycardia, either spontaneously with time or induced by ischemia or antiarrhythmic drugs, can contribute to the clinical occurrence of sustained ventricular arrhythmias in patients with an old myocardial infarction.

Eligibility for and benefit of thrombolytic therapy in inferior myocardial infarction: focus on the prognostic importance of right ventricular infarction.

OBJECTIVES: This study was undertaken to determine eligibility for and benefit of thrombolytic therapy in patients with acute inferior myocardial infarction with or without right ventricular involvement. BACKGROUND: Right ventricular involvement commonly complicates acute inferior myocardial infarction and is considered to have prognostic relevance. We hypothesized that the presence of right ventricular infarction, diagnosed early by ST segment elevation in the right precordial lead (V4R), may be of clinical importance in identifying patients who will benefit most from thrombolytic therapy. METHODS: We studied 200 consecutive patients with acute inferior myocardial infarction to assess the prognostic impact of right ventricular infarction in those considered eligible or ineligible for reperfusion therapy. Prognostic analyses were based on the in-hospital period and a 1- to 6-year follow-up (mean [+/- SD] 37 +/- 12 months). RESULTS: ST segment elevation in lead V4R was a reliable marker of right ventricular infarction (sensitivity 88%, specificity 78%, diagnostic efficiency 83%) in 107 patients (54%) with inferior myocardial infarction. Seventy-one eligible patients (36%) received thrombolytic therapy and had a lower mortality (8% [6 of 71]) and complication (31% [22 of 71]) rate than ineligible patients (mortality rate 25% [32 of 129], p < 0.01; complication rate 56% [72 of 129], p < 0.01). However, the overall benefit of thrombolysis was restricted to patients with right ventricular infarction complicating acute inferior myocardial infarction (with vs. without thrombolysis, respectively: mortality rate 10% vs. 42%, p < 0.005; complication rate 34% vs. 54%, p < 0.05). In the absence of right ventricular infarction, no difference was observed in the mortality (7% vs. 6%, p = NS) and major in-hospital complication (27% vs. 29%, p = NS) rates, whether or not the patient underwent thrombolytic therapy. Posthospital course over 37 +/- 12 months was not different in patients with and without right ventricular infarction but was best in all patients considered for reperfusion therapy. CONCLUSIONS: During acute inferior myocardial infarction, the right precordial electrocardiogram is a simple but promising variable to identify a subgroup of patients with an unfavorable course who will benefit most from thrombolytic therapy.

Propafenone during acute myocardial ischemia in patients: a double-blind, randomized, placebo-controlled study.

OBJECTIVES: The proarrhythmic risk of class I antiarrhythmic agents in combination with myocardial ischemia is mainly the result of their effects on ventricular repolarization. This study was designed to evaluate the effect of class Ic antiarrhythmic agents on QT dispersion during myocardial ischemia. BACKGROUND: QT interval dispersion on the 12-lead electrocardiogram (ECG) has been suggested as a noninvasive marker of inhomogeneous ventricular repolarization and susceptibility to ventricular arrhythmias. METHODS: In a randomized, double-blind study, 98 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) were pretreated with propafenone or placebo. QT dispersion was defined as a maximal minus minimal QT interval on the 12-lead ECG before and after PTCA. The power of the study to detect clinically meaningful differences in QT dispersion was 0.75, and a twofold increase in QT dispersion in the propafenone group compared with the placebo group was considered clinically relevant. RESULTS: The QT and corrected QT (QTc) intervals increased significantly during occlusion of the left anterior descending coronary artery (LAD) (9% and 11%, respectively, p < 0.05), whereas occlusion of the circumflex and right coronary arteries had no effect. QTc dispersion increased significantly in the propafenone group during ischemia (+52%, p = 0.002, vs. +23%, p = 0.15). The most considerable effect on QT dispersion was observed during LAD occlusion and ischemia of the anterior wall (+74%, p = 0.025). Corrected JT dispersion (+57%, p = 0.017, vs. +24%, p = 0.23) and the QT dispersion ratio (+1.6%, p = 0.031, vs. 0.9%, p = 0.34) showed similar effects. Plasma levels of propafenone (522 +/- 165 micrograms/liter) did not influence the results. CONCLUSIONS: During myocardial ischemia, particularly during LAD occlusion, propafenone results in a significant increase in QT dispersion. The results indicate that QT interval prolongation and enhanced QT dispersion reflect inhomogeneous ventricular repolarization generated by the ischemic anterior wall of the myocardium. These observations may demonstrate a clinically important interaction between myocardial ischemia, repolarization variables and propafenone.

Antiarrhythmic effects of increasing the daily intake of magnesium and potassium in patients with frequent ventricular arrhythmias. Magnesium in Cardiac Arrhythmias (MAGICA) Investigators.

OBJECTIVES: This study sought to assess potential antiarrhythmic effects of an increase in the daily oral intake of magnesium and potassium in patients with frequent ventricular arrhythmias. BACKGROUND: Magnesium and potassium contribute essentially to the electrical stability of the heart. Despite experimental and clinical evidence for the antiarrhythmic properties of the two minerals, controlled data in patients with stable ventricular arrhythmias are lacking. METHODS: In a randomized, double-blind study, 232 patients with frequent ventricular arrhythmias (> 720 ventricular premature beats [VPBs]/24 h) confirmed at baseline and after 1 week of placebo therapy were subsequently treated over 3 weeks with either 6 mmol of magnesium/12 mmol of potassium-DL-hydrogenaspartate daily or placebo. RESULTS: Compared with placebo pretreatment, active therapy resulted in a median reduction of VPBs by -17.4% (p = 0.001); the suppression rate was 2.4 times greater than that in patients randomized to 3 weeks of placebo therapy (-7.4%, p = 0.038). The likelihood of a > or = 60% (predefined criterion) or > or = 70% suppression rate (calculated from the placebo-controlled run-in period) was 1.7 (25% vs. 15%, p = 0.044) and 1.5 times greater in the active than in the placebo group (20% vs. 13%, p = 0.085), respectively. No effect of magnesium and potassium administration was observed on the incidence of repetitive and supraventricular arrhythmias and clinical symptoms of the patients. CONCLUSIONS: To our knowledge, this study is the first to provide controlled data on the antiarrhythmic effect of oral administration of magnesium and potassium salts when directed to patients with frequent and stable ventricular tachyarrhythmias. A 50% increase in the recommended minimum daily dietary intake of the two minerals for 3 weeks results in a moderate but significant antiarrhythmic effect. However, with the given therapeutic regimen, repetitive tachyarrhythmias and patient symptoms remain unchanged.

Effects of early reperfusion in acute myocardial infarction on arrhythmias induced by programmed stimulation: a prospective, randomized study.

This study compares inducibility of ventricular tachyarrhythmias by programmed electrical stimulation of the heart in patients with myocardial infarction with and without reperfusion after streptokinase therapy. Sixty-two consecutive patients admitted with an acute myocardial infarction were randomized to either combined intravenous and intracoronary streptokinase (streptokinase group) or to standard coronary care unit treatment (control group). Thirty-six of the 62 patients (21 patients from the streptokinase and 15 from the control group) with a first myocardial infarction were studied by programmed ventricular stimulation after a mean of 26 +/- 14 days. No patient had a history of antiarrhythmic drug use or documentation of a ventricular arrhythmia before the initial admission. A sustained ventricular arrhythmia was induced in 10 (48%) of the 21 patients randomized to streptokinase therapy and in all 15 (100%) control patients (p less than 0.001). Sustained monomorphic ventricular tachycardia was induced in 6 (29%) and 10 (67%) patients, respectively (p less than 0.05). To terminate an induced arrhythmia, direct current countershock was required in 33% of patients in the streptokinase group and 73% of patients in the control group (p less than 0.02). Seventeen of the 21 patients treated with streptokinase and no control patient had evidence of early reperfusion 200 +/- 70 minutes after the onset of pain. In comparison with patients without early reperfusion, patients in the reperfused group had a lower maximal serum creatine kinase value (p less than 0.01), a shorter time to peak creatine kinase value (p less than 0.001) and a higher angiographic left ventricular ejection fraction (62 versus 45%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy and tolerance of the new class IB antiarrhythmic barucainide: an intravenous dose-finding study.

Barucainide is a new class IB antiarrhythmic agent that was studied for efficacy and safety after intravenous administration in patients with severe ventricular arrhythmias. All patients received 80 mg/hr barucainide intravenously for 7 hours or until ventricular arrhythmias were suppressed by greater than 90%. In responders a maintenance dose was given for 24 hours, aimed to achieve steady-state conditions. At baseline and during the treatment and washout periods 24-hour Holter recordings were performed. In addition, electrocardiogram, blood pressure, and plasma concentration of barucainide were measured. In 9 of 12 patients dose titration was effective (mean dose, 185 mg). In six of nine patients arrhythmia suppression persisted during maintenance therapy (mean dose, 18 mg/hr). Plasma concentrations correlated with given doses, rather than with antiarrhythmic efficacy. During the washout period, five patients required more than 12 hours for recurrence of arrhythmias. Treatment was stopped in one patient because of proarrhythmia; one patient had moderate heat sensations. Thus barucainide is a potent class IB agent, with a favorable side effect profile.

Prediction of efficacy and tolerance of oral mexiletine by intravenous lidocaine application.

In a controlled crossover trial, 15 patients with frequent ventricular arrhythmias were treated with lidocaine to predict efficacy and safety of oral mexiletine. After an initial control period, patients received intravenous lidocaine (bolus infusion of 200 mg/20 min followed by 3.6 gm/24 hr and for 7 days oral mexiletine (200 mg four times a day). Efficacy was controlled by 24-hour Holter monitoring (responders = suppression of single premature ventricular beats [PVB] greater than 84% and of complex PVB greater than 90%). After lidocaine, 10 of 15 patients (67%) were responders (mean PVB reduction: 97%). After mexiletine, five of 15 patients (33%) were responders (mean PVB reduction: 81%); efficacy was closely related to the plasma concentration. When efficacy of both agents was compared, lidocaine infusion had a positive predictive value of only 50%; however, the negative predictive value was 100%. Thus in nonresponders to lidocaine, mexiletine is very likely to fail in the suppression of ventricular ectopy.

Comparison of twice daily with thrice daily administered encainide for benign or potentially lethal ventricular arrhythmias.

The antiarrhythmic efficacy of encainide administered 2 (group A) or 3 times daily (group B) was evaluated in a randomized, placebo-controlled trial involving 101 patients with benign or potentially malignant ventricular arrhythmias. In group A, encainide was titrated at dosages of 35, 50 and 75 mg twice daily and in group B at dosages of 25, 35 and 50 mg 3 times daily. Drug efficacy, as judged by repeated ambulatory monitoring, was defined as greater than 75% reduction in ventricular premature complexes combined with a greater than 90% abolition of pairs and runs of nonsustained ventricular tachycardia. In group A, 27 of 52 patients (52%) had their arrhythmia suppressed by the drug compared with 34 of 49 (69%) in group B (difference not significant). There was a trend toward better arrhythmia control in group B if a total daily dose of greater than 100 mg was necessary for arrhythmia suppression. Side effects were frequent in both groups (24 vs 28%, difference not significant). Thus, encainide administered twice daily effectively suppresses ventricular arrhythmias in this patient population.

Dysrhythmias after direct-current cardioversion.

The success rate of direct-current (DC) countershocks and postshock arrhythmias are of concern for the design of automatic devices. Results of 112 DC shocks for induced ventricular tachycardia/fibrillation (VT/VF) (n = 99) or atrial fibrillation (AF) were analyzed. Clinical and arrhythmia characteristics were related to the success rate of DC shocks as well as postshock arrhythmias. Sixty-one patients were men and 14 were women; mean age was 52 +/- 15 years. Coronary artery disease was present in 56 patients and cardiomyopathy in 4. The other patients had no apparent structural heart disease. The success rate of transchest DC shocks for VT and VF were identical. The first DC shock interrupted 80% of VT and VF episodes. All episodes were terminated by 4 or fewer DC shocks. A single DC shock changed morphologic pattern or rate of 4 episodes of VT. Asystole after VT/VF (1,900 +/- 960 ms) was longer than after atrial fibrillation (1,150 +/- 470 ms, p less than 0.01). VT/VF recurred (within 3 minutes) after 26 of 99 initially successful DC shocks, requiring repeat shocks in 2 cases. Sinus bradycardia (n = 18) or high degree atrioventricular block (n = 11) necessitated rate support pacing in 10 patients. Antiarrhythmic drugs did not prevent postshock tachycardias, but facilitated the development of bradycardias. In conclusion, reliable and continuous analysis of cardiac rhythm after discharge is mandatory to enable automatic devices to correct unsuccessful discharges or recurring VT/VF. In addition, demand pacing capability is desirable to prevent severe bradycardia after DC shocks in patients receiving antiarrhythmic drugs.

Programmed electrical stimulation in healed myocardial infarction using a standardized ventricular stimulation protocol.

The diagnostic accuracy of programmed electrical stimulation was prospectively assessed in 111 patients with myocardial infarction (MI) with or without a history of spontaneous ventricular arrhythmias. In 29 patients neither ventricular tachycardia (VT) nor episodes of 10 premature ventricular depolarizations per hour was documented. Fifty patients had documented nonsustained VT and 32 had sustained monomorphic VT. One and 2 extrastimuli (twice diastolic threshold, 2 ms in duration) were given during sinus rhythm and ventricular pacing at 100, 120 and 140 beats/min in the right ventricular apex (part I). When this protocol failed to induce a sustained monomorphic VT, a third extrastimulus was introduced (part II). Repetitive ventricular responses were induced in all patients, and in 15 (14%) polymorphic ventricular arrhythmias requiring DC shock were induced. Incidence of initiation of sustained monomorphic VT and polymorphic ventricular arrhythmias requiring DC shock was related to the clinical arrhythmia and the stimulation protocol. In patients with documented sustained monomorphic VT, a third extrastimulus only increased the incidence of sustained monomorphic VT (68% to 94%), whereas in patients with documented nonsustained VT and without VT the incidence of both polymorphic and monomorphic arrhythmias increased by 7 to 12%. Sustained monomorphic VTs induced in patients without such a history were faster (p less than 0.01), depended on site of MI (p less than 0.05) and were more often preceded by nonsustained polymorphic VT (p less than 0.01) than in patients with documented sustained monomorphic VT.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias induced during termination of supraventricular tachycardia.

Pacing is being used frequently for the treatment of drug-resistant, paroxysmal supraventricular tachycardias (SVT). SVT can usually be terminated by pacing, but arrhythmias may be induced which interfere with the safety of antitachycardia pacing. To quantify these pacing-induced arrhythmias, 453 attempts to terminate SVT in 111 patients were analyzed. The patients were 6 to 73 years old (mean 41); 62 were male. Seventy-six patients had SVT using an accessory atrioventricular bypass, and 35 patients had intranodal SVT. Single and then, if required, multiple ventricular and atrial premature beats and overdrive pacing were delivered from the atrium and ventricle. A pacing-induced arrhythmia occurred in 9% of all attempts (34% of patients). Atrial flutter or fibrillation (AF) was the most frequent arrhythmia (in 8% of all attempts and sustained in 75%). Atrial vs ventricular pacing resulted in a 12% vs 2% incidence of AF. AF was unrelated to age, sex, atrial size and SVT type, and was predominantly induced by multiple premature beats. In 6 patients a different SVT and in 2 patients a nonsustained ventricular tachycardia was induced. In 6 patients SVT could only be terminated by initiating another arrhythmia. Thus, AF is frequently induced during attempted pacing termination of SVT. To limit the risk of AF, a single premature beat should preferentially be used to terminate SVT. In 6% of patients, SVT can only be terminated by inducing another arrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence and clinical relevance of QT prolongation caused by the new selective serotonin antagonist ketanserin.

Efficacy and safety of ketanserin were studied prospectively in a randomized, double-blind trial involving 221 patients treated for hypertension or coronary artery disease, or both. Since ketanserin has been suggested to cause QTc prolongation, the incidence and severity of this effect were investigated, as was the incidence of malignant ventricular arrhythmias during Holter monitoring. After a 1-week run-in period, all patients were examined: blood pressure was measured and electrocardiograms and 24-hour Holter electrocardiograms were obtained. Two thirds of the patients (n = 147) were then randomized to receive ketanserin for 1 week (20 mg twice daily) followed by 3 weeks of 40 mg twice daily; one third of the patients (n = 74) received placebo (twice daily) for 4 weeks. After 4 weeks of treatment, blood pressure, electrocardiograms and 24-hour Holter electrocardiograms were repeated. In hypertensive patients, ketanserin significantly reduced systolic (mean reduction 17 +/- 2 mm Hg, p less than 0.0001) and diastolic blood pressure (12 +/- 1 mm Hg, p less than 0.0001) compared to baseline, and to the placebo group (p less than 0.005 for systolic and diastolic blood pressure). The QTc interval was prolonged with ketanserin (mean 400 to 418 ms, p less than 0.01) but not with placebo (399 vs 402 ms). In the ketanserin group 30% of patients and in the placebo group 8% of patients had QTc prolongation greater than 30 ms (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiologic characteristics of ventricular tachycardia or fibrillation in relation to age of myocardial infarction.

Evaluation of ventricular myocardium after the onset of acute myocardial infarction (AMI) suggests that the substrate for ventricular arrhythmias changes as the substrate for ventricular arrhythmias changes as the AMI heals. To determine if the ability of programmed stimulation to initiate ventricular tachycardia (VT) varies according to the interval between AMI and electrophysiologic testing, the clinical and electrophysiologic data of 42 patients with spontaneous sustained VT and 12 patients with ventricular fibrillation (VF) more than 3 days after a single AMI were analyzed. For patients with VT, there were no significant differences in the incidence of initiation of sustained monomorphic VT among those evaluated 1 to 3 weeks (100%), 3 to 8 weeks (75%), 2 to 6 months (100%), 6 to 18 months (80%) or more than 18 months (81%) after AMI, and the mean number of extrastimuli required for initiation did not differ among the groups. Patients evaluated more than 4 weeks after the initial episode of VT had a lower incidence of inducible VT than those studied earlier (14 of 21 [71%] vs 21 of 21 [100%], p less than 0.05), although this appeared to be a result of earlier termination of the stimulation protocol owing to initiation of polymorphic arrhythmias in those studied later. The 14 patients evaluated within 8 weeks of AMI had significantly faster VT rates (mean cycle length 269 +/- 45 ms) than the 28 patients studied later (320 +/- 75 ms, p less than 0.01), possibly because of more out-of-hospital presentations of VT in patients studied later.(ABSTRACT TRUNCATED AT 250 WORDS)

Importance of modes of electrical termination of ventricular tachycardia for the selection of implantable antitachycardia devices.

Different implantable systems for electrical treatment of ventricular arrhythmias are available. Information about mode of termination of ventricular tachycardia (VT) helps to select the most appropriate electrical treatment for drug-resistant VT. During 158 electrophysiologic studies, the mode of termination of 215 episodes of VT was analyzed in 2 groups of patients. Group 1 consisted of 54 patients with documented monomorphic VT and group 2 of 46 patients with other documented or suspected ventricular arrhythmias. Eighty-two patients had coronary heart disease, 8 had other structural heart disease and 10 had idiopathic VT. Termination of VT was attempted using extrastimuli and overdrive pacing; direct-current (DC) shocks were given in case of syncopal VT. During 33 of 96 studies (34%) in group 1, DC shock was required to interrupt VT, compared with 45 of 62 studies (73%) in group 2 (p less than 0.001). This difference was a result of less frequent induction of immediately syncopal VT in group 1 (14 of 129 VTs, vs 40 of 86 in group 2, p less than 0.001). Non-syncopal VT could reliably and safely be terminated by pacing in 61%, irrespective of the clinical arrhythmia. Pacing-induced acceleration of VT occurred in 6% (single extrastimuli) to 36% (over-drive pacing) (mean 26%) of attempts. Subsequent DC shock was required in half of these cases. Immediate collapse after induction of VT was not related to the presence of heart disease, but was related to a combination of VT cycle length (shorter than 260 ms) and left ventricular ejection fraction (less than 40%). Antiarrhythmic drugs reduced the need for DC shock.(ABSTRACT TRUNCATED AT 250 WORDS)

Time course and interrelation of reperfusion-induced ST changes and ventricular arrhythmias in acute myocardial infarction.

With the increasing use of thrombolytic therapy, the presence and time course of reperfusion-induced ventricular arrhythmias and ST-segment changes have become of particular interest. Technical improvements in bipolar Holter monitoring offer the opportunity to record both parameters continuously and simultaneously. Time course and interaction of both parameters in dependence on the onset of thrombolysis and time of reperfusion were investigated in 30 patients with acute myocardial infarction. Reperfusion was achieved in 20 patients after 49 +/- 23 minutes and in another 2 patients after 120 minutes (73%, group A). Vascular occlusion persisted in 8 patients for greater than 24 hours (group B). Sudden ST-segment changes (greater than 0.2 mV/15 min) in the bipolar leads indicated reperfusion in 7 of 22 patients (32%). Idioventricular rhythms, most frequent in reperfused patients (group A: 18 of 22 patients, mean 121 beats/hour), were unspecific reperfusion markers (group B: 5 of 8 patients, 1 beat/hour) unless frequent (p less than 0.05) or longer lasting, repetitive (p less than 0.01) episodes were considered. Premature ventricular beats and couplets (p less than 0.05) were also most frequent in group A (peak frequency 3 to 5 hours after thrombolysis). Ventricular tachycardia observed in 21 of 22 patients (95%) in group A and in 3 of 8 (38%) in group B (p less than 0.01) attained their peak frequency 7 to 9 hours after thrombolysis. They occurred most often in anterior myocardial infarction and were often preceded by frequent singular premature beats (r = 0.78).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term antiarrhythmic therapy with flecainide.

The antiarrhythmic efficacy and safety of oral flecainide were assessed during a controlled 2-week and a subsequent 48-week long-term trial. Fifteen patients with frequent (more than 30 per hour) and complex ventricular arrhythmias (Lown grade IVA or IVB) who had been resistant or intolerant to 2 or more antiarrhythmic agents, were included in the study. Antiarrhythmic efficacy was controlled by 24-hour Holter monitoring at 2, 12, 24 and 48 weeks. The administration of 100 to 200 mg flecainide twice daily resulted in more than 90% suppression of VPCs and of complex ventricular arrhythmias in 14 of 15 patients. The minimum effective therapeutic dose could be titrated in 9 of 14 patients to 100 mg twice daily, in 3 of 14 patients to 150 mg twice daily and in 2 of 14 patients to 200 mg twice daily. During this therapy and a mean plasma concentration of 886 +/- 103 ng/ml, PQ and QRS duration, as well as QTc time and JTc interval were not significantly changed. Side effects (gastrointestinal complaints, nausea, obstipation, dizziness, visual disturbances, headache and impaired potency) were seen in 5 of 14 patients after 12 weeks, in 3 of 4 patients after 24 weeks and in only 2 of 14 patients after 48 weeks. Side effects were described as mild and tolerable and did not limit flecainide therapy except in 1 patient, who had discontinued therapy with flecainide after 3 days because of intense gastrointestinal symptoms. In conclusion, flecainide is highly effective and well tolerated in the long-term treatment of serious ventricular arrhythmias.

Determinants of prognosis in idiopathic dilated cardiomyopathy as determined by programmed electrical stimulation.

The incidence and prognostic significance of electrically induced ventricular arrhythmias were prospectively assessed in 42 patients with idiopathic dilated cardiomyopathy. All patients underwent 24-hour, long-term electrocardiographic (Holter) monitoring and 30 were analyzed by a signal-averaging vectorcardiographic procedure at entry into the study. Their response to programmed electrical stimulation during basic right ventricular pacing was investigated using 1 and 2 ventricular extrastimuli. A monomorphic tachycardia was not induced in any patient. In 36 patients (86%) polymorphic ventricular arrhythmias were initiated. Three or more induced consecutive ventricular premature complexes occurred in 9 patients (21%), nonsustained polymorphic ventricular tachycardia in 2 (4.8%) and ventricular fibrillation in 1 patient (2.4%). There was no association between electrically induced polymorphic ventricular arrhythmias and the degree of impairment of left ventricular function. Furthermore, the incidence of induced ventricular arrhythmias was not related to the Lown grade or to the total number of ventricular premature complexes during Holter monitoring. A late potential was detected by the averaged vectorcardiogram in only 1 of the 30 patients. During follow-up (mean 16 +/- 7 months) 7 patients died, 5 from chronic congestive heart failure and 2 from sudden cardiac death. No patient had an electrically induced arrhythmia of 3 or more ventricular premature complexes.(ABSTRACT TRUNCATED AT 250 WORDS)