Orally administered prajmalium bitartrate in acute and chronic ventricular arrhythmias.

The effect of orally administered prajmalium bitartrate on premature ventricular complexes and on runs of such complexes was studied in 42 patients. Ventricular extrasystoles were quantified from stored continuous electrocardiographic tape recordings using a semiautomated arrhythmia-detection system. In 19 patients prajmalium bitartrate was given at a dose of 80 mg/24 hours (20 mg every 6 hours). Premature ventricular contractions decreased significantly. Two hours after administration of the drug, the frequency of premature ventricular complexes was reduced to 63 percent of the intial rate. After 6 hours the full drug effect was attained. After 12 hours the number of premature ventricular complexes averaged 30 percent of the initial value. During the succeeding drug-free interval the frequency of premature ventricular complexes increased and reached 57 percent of the initial value after 10 hours.In a second group of 14 patients each patient was treated with prajmalium bitartrate and procainamide (3 g/24 hours) for comparison of drug effects. No significant differences were found in the antiarrhythmic action of the two drugs. Prajmalium bitartrate was well tolerated by all patients. However, three patients receiving procainamide complained of nausea and gastrointestinal symptoms and two of them had to discontinue therapy. One patient receiving long-term procainamide therapy experienced reversible joint pains of a lupus erythematosus-like syndrome.In a third group of 23 patients with acute myocardial infarction 9 patients were given prajmalium bitartrate, 20 mg 3 times every 4 hours; 14 patients (control group) received no antiarrhythmic drug. In the control group premature ventricular complexes increased continuously up to the 10th hour after infarction and slowly decreased thereafter. Prajmalium bitartrate reduced the rate of premature ventricular complexes significantly to a mean of 4 percent of the initial value. In the untreated patients the rate decreased only to 60 percent of the initial value. Runs of premature ventricular complexes were suppressed immediately after administration of prajmalium bitartrate, whereas in the control group the frequency of such runs ranged between 80 and 140 percent of the initial value. These findings document the effective antiarrhythmic action of orally administered prajmalium bitartrate on premature ventricular complexes.     

Malignant ventricular arrhythmias are well tolerated in patients receiving long-term left ventricular assist devices

Objectives. We sought to quantitate the incidence of malignant ventricular arrhythmias and to identify subsequent hemodynamic changes and untoward events in patients who have received an implantable left ventricular circulatory assist device as an extended bridge to heart transplantation.Background. Implantable long-term mechanical circulatory assist devices have been used clinically with increasing frequency and success for the past 4 years. Previous investigators have suggested that patients with malignant ventricular arrhythmias receiving a left ventricular assist device will require both left and right ventricular assistance to maintain vital organ perfusion.Methods. We reviewed our 4-year experience with 21 patients who underwent implantation of a left ventricular assist device. Device flows and mean arterial pressure were used to assess systemic perfusion; central venous pressure provided a gauge of right ventricular function. Charts were screened for evidence of end-organ injury resulting from malignant ventricular arrhythmias.Results. Malignant ventricular arrhythmias occurred in 4 patients (19%) before device placement and in 9 patients (43%) during device support. The latter nine patients formed the final study group; their arrhythmias occurred 0 to 186 days after device implantation and had a duration of 10 min to 12 days. The patients reported weakness or palpitation; however, none reported syncope or dyspnea. Mean arterial pressure and central venous pressure were insiganificantly changed by the arrhythmias. Device flow decreased by 1.4 ± 0.6 liters/min (p < 0.05) at the onset of the arrhythmias but returned to normal after cardioversion. No thromboembolic events or significant end-organ dysfunction occurred.Conclusion. Absence of right ventricular contraction during malignant ventricular arrhythmias is well tolerated in recipients of a left ventricular assist device. The diagnosis of malignant arrhythmia should be suspected if an unexplained decrease in left ventricular assist device flow occurs. Early electrical cardioversion is warranted to avoid both thrombus formation in the native heart and right ventricular myocardial injury from prolonged fibrillation.     

Ventricular arrhythmias and left ventricular myocardial function in chronic chagasic patients

To study the relationship of complex ventricular arrhythmias to the presence and extent of myocardial damage, 556 chronic chagasic patients were submitted to an extensive protocol, including left ventricular cineangiography and Holter monitoring, and properly classified according to clinical, electrocardiographic and hemodynamic findings. Stages of the clinical-hemodynamic classification corresponded to increasing degrees of myocardial damage, age, prevalence and complexity of ventricular arrhythmias. Myocardial damage (particularly left ventricular dilatation) was the most important clinical factor linked to the presence of complex ventricular arrhythmias. A clear difference in terms of ventricular function was found only when arrhythmias were grouped into simple (Lown grades I and II) and complex (grades III and IV) forms. It is recommended that any classification for chagasic patients must be based on signs of myocardial involvement, instead of clinical or electrocardiographic findings alone. Evaluation should include accurate determination of left ventricular myocardial function, along with the search for the presence of complex ventricular arrhythmias and abnormalities of conduction.     

Flecainide: one-year efficacy in patients with chronic ventricular arrhythmias

During a one-week short-term in-hospital period, 60 patientswith chronic ventricular arrhythmias were treated with 200 mgflecainide twice a day. Flecainide reduced premature ventricularcomplexes (PVCs) by more than 85% without causing importantside-effects in 47 patients, who entered a one-year follow-upperiod and were followed with bimonthly 24-h ECGs. Median PVC-frequencyremained reduced by more than 99% during the follow-up period.Repetitive ventricular beats and ventricular tachycardia werepresent in 83% and 42% of patients, respectively, before flecainide.During follow-up, these arrhythmias were seen in less than 32%and less than 10% of patients, respectively, at each 24-h ECG.Furthermore, the mean number of hours with repetitive ventricularbeats and ventricular tachycardia remained reduced by more than76% and more than 79%, respectively, throughout the follow-upperiod. Ventricular arrhythmias remained suppressed despitea gradual reduction in flecainide dosages (to a median of 300mg day^–1) and flecainide plasma levels. In nine out of47 patients, an increase in ventricular arrhythmias above baselinevalues on one or more occasions was observed. During a flecainidewithdrawal period, a 65-fold increase in median PVC-frequencywas observed and ventricular tachycardia reappeared in 18 patients.Subjective side-effects were acceptable except for two patients.During the follow-up period, one patient developed reversibleheart failure and sinus node dysfunction. During the total studyperiod, four patients, with either severe coronary artery disease(2) or cardiomyopathy (2) developed lethal arrhythmias (3) orischaemic events (1). We conclude that prolonged flecainidetreatment is effective in a high proportion of patients withchronic ventricular arrhythmias. In some patients an arrhythmogeniceffect may occur.     

Multiple comparison of several antiarrhythmic agents by acute oral drug testing in patients with chronic ventricular arrhythmias

This study addresses the question of the choice of treatmentfor the individual patient with chronic ventricular arrhythmias.Acute oral drug testing offers a pragmatic approach to the rapidselection of the drug with the best efficacy/side-effect ratioby allowing multiple comparisons within the same patient. Fortypatients with chronic ventricular arrhythmias received a singleoral dose of the following antiarrhythmic drugs: flecainide200 mg, propafenone 450 mg, disopyramide 300 mg, mexiletine400 mg, tocainide 800 mg, verapamil 160 mg, propranolol 120mg. Criteria for efficacy were suppression of complex ventriculararrhythmias and a > 90% reduction in premature ventricularbeats lasting for at least 2 h. An antiarrhythmic effect was achieved with each of the drugsin the following percentages of patients: flecainide 69·;4%,propafenone 67·5%, disopyramide 54·;8%, mexiletine45·2%, tocainide 31·;3%, verapamil 31·3%,propranolol 12·5%. In no case was worsening of arrhythmiaobserved. At the end of the acute testing phase, the drug thathad proved most effective in each patient was administered ata full dosage for 72 h. A concordant response between the twophases was observed in 80% of patients and was as high as 89%when the analysis was limited to flecainide and propafenone. This study shows the feasibility and practical advantages forpatient management of a multiple comparison of antiarrhythmicdrugs by acute oral drug testing. It also provides, in a non-invasivecost-effective manner, unique insights into the complex relationshipbetween drug characteristics, individual responses and clinicalefficacy.     

Effect of acute hemodynamic decompensation on electrical inducibility of ventricular arrhythmias in patients with dilated cardiomyopathy and complex nonsustained ventricular arrhythmias

In patients with dilated cardiomyopathy, hemodynamic decompensation has been postulated to increase vulnerability to reentrant ventricular arrhythmias. To test this hypothesis, we performed programmed ventricular stimulation with three extrastimuli on nine patients with dilated cardiomyopathy and asymptomatic complex ventricular arrhythmias during a period of acute hemodynamic decompensation; programmed ventricular stimulation was then repeated following hemodynamic improvement with nitroprusside. These patients did not have a history of documented or suspected sustained ventricular tachycardia or fibrillation. The mean left ventricular ejection fraction was 0.21 +/- 0.04 (range 0.15 to 0.26). In the baseline state, mean right atrial pressure was 8 +/- 4 mm Hg, pulmonary artery wedge pressure was 20 +/- 3 mm Hg, and cardiac index was 3.2 +/- 0.5 L/min/m2. Following acute hemodynamic decompensation, mean right atrial pressure increased to 16 +/- 5 mm Hg and pulmonary artery wedge pressure to 33 +/- 8 mm Hg; cardiac index decreased to 2.1 +/- 0.5 L/min/m2. In this decompensated state, programmed ventricular stimulation failed to induce sustained or nonsustained ventricular arrhythmias in any patient. Following nitroprusside administration (mean dose 1.5 +/- 1.1 micrograms/kg/min), there were significant decreases in mean right atrial pressure (11 +/- 3 mm Hg) and pulmonary artery wedge pressure (16 +/- 3 mm Hg), and a significant increase in cardiac index (3.1 +/- 1.1 L/min/m2) (p less than 0.05 for all values versus the decompensated state). In the improved hemodynamic state, programmed ventricular stimulation induced nonsustained ventricular tachycardia (six beats) in only one patient, and sustained arrhythmias in none.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative efficacy of short-term intravenous infusions of milrinone and dobutamine in acute congestive heart failure following acute myocardial infarction

The purpose of this study was to compare the hemodynamic and clinical effects of milrinone, a vasodilating and positive inotropic agent, with those of dobutamine in patients with congestive heart failure (CHF) following acute myocardial infarction (AMI). Thirty-three patients in Killip classification II or III within 12 h to 5 days after AMI were randomized in a multicenter, open-label clinical trial to receive a 24-h infusion of milrinone or dobutamine. Drugs were titrated to achieve at least a 30% increase in cardiac index (CI) from mean baseline or at least a 25% decrease in mean pulmonary capillary wedge pressure (MPCWP) from baseline. Both drugs improved CI, MPCWP, and other hemodynamic parameters. Criteria for decrease in MPCWP were met by 94% (15/16) of the milrinone-treated patients and 57% (8/14) of dobutamine-treated patients (p = 0.03). Both groups met the minimum efficacy criterion for CI. Maximal reduction in MPCWP over 0–3 h was greater in the milrinone group (-53.2%) than in the dobutamine group (-31.0%; p ≤ 0.01); reductions were sustained over 24 h. Both drugs improved echocardiographic global ejection fraction and were generally well tolerated. The short-term infusion of milrinone may have a role in the management of CHF following AMI, especially when the aim is the rapid reduction of pulmonary congestion.     

Efficacy and tolerance of intravenous flecainide in patients with chronic high frequency ventricular arrhythmias

The effectiveness and safety of intravenous flecainide was evaluatedin 33 patients with chronic high frequency premature ventricularcomplexes (mean value of PVCs 23.7 min^–1). Flecainidewas injected intravenously at a rate of 20 mg per 2 min untilcomplete disappearance of ventricular arrhythmias or up to atotal dose not exceeding 200 mg. Total suppression of PVCs occurredin 31 out of 33 patients at the end of the injection (mean dose132 mg). The overall reduction of PVCs was 94 per cent (P>0.001)at the end of infusion and 74 per cent (P>0.001) 1 h later.The mean plasma drug level attained 1 h after administrationwas 287 ng ml^–1 (range 82–984). Heart rate and bloodpressure did not change, but a significant increase (P>0.001)in PR (+12%), QRS (+13%) and QTc (+4%) duration occurred afterdrug administration. Flecainide was well tolerated. An idioventriculartachycardia was induced in one patient and two patients experiencedside effects of the central nervous type: dizziness, blurringof vision and a sensation of warmth. In view of its activityflecainide appears to be a valuable addition to the antiarrhythmicarmamentarium.     

Treatment and prophylaxis of ventricular arrhythmias in acute myocardial infarction

Remarkable advances have been made in the management of cardiac disease in the last 20 years, but antiarrhythmic drug strategy in the acute phase of myocardial infarction remains less than satisfactory. Primary ventricular fibrillation (VF), once considered predictable on the basis of detection of “warning arrhythmias,” cannot be anticipated. Management must be either expectant or prophylactic. Restriction of drug use to selected patients and the apparent lack of effect of VF on late prognosis argue for the former approach, yet safe and effective prevention of VF is an attractive therapeutic goal. High-dose intravenous lidocaine probably offers efficacy but the risk-benefit ratio of this regimen is still debated. Adoption of a prophylactic regimen mandates drug administration to a large number of patients who either are not at risk of developing VF (noninfarct patients) or who are destined not to develop VF (70 to 95% of infarct patients). Ventricular arrhythmias other than VF are common in acute infarction and, for emotional rather than scientific reasons, often are aggressively treated. Little evidence exists to support this management. Few ventricular arrhythmias at this time in infarction have either immediate importance or prognostic significance. Reevaluation of antiarrhythmic drug use and arrhythmia treatment in acute myocardial infarction is long overdue. However, there is a paucity of controlled data upon which to base new strategies, and clinical research in this field is hampered by ethical considerations, by rigidly held but unscientifically based beliefs and by a lack of fundamental knowledge of arrhythmia mechanisms and their significance.     

慢性收缩性心力衰竭患者室性心律失常的特点及影响因素

目的 了解慢性收缩性心力衰竭(chronic systolic heart failure,CSHF)住院患者室性心律失常的发生特点及影响因素.方法 回顾性调查和分析湖北地区8地市共12家三级甲等医院2000年至2010年CSHF住院患者资料,单因素和多因素logistic回归分析室性早搏(室早)和室性心动过速(室速)相关危险因素.根据年龄将患者分为≤40岁、41～50岁、51～60岁、61～70岁、71～80岁和≥81岁组;根据心功能分为Ⅰ、Ⅱ、Ⅲ、Ⅳ级(NYHA分级)组;根据左心室射血分数(LVEF)将患者分为LVEF0.41 ～0.50、0.31～0.40、0.21 ～0.30和≤0.20组;根据心力衰竭病因将患者分为冠心病、风湿性心脏病(风心病)、高血压性心脏病(高心病)和扩张型心脏病(扩心病)组.结果 ①CSHF患者室早和室速的发生率分别为68.30％和14.52％.②多因素logistic回归分析发现:室早和室速的发生风险(HR)在各年龄组间差异无统计学意义;不同心功能组间差异无统计学意义;与冠心病组相比,风心病、高心病和扩心病组室早和室速HR分别为0.430(95％ CI,0.381～0.497,P＜0.01)、0.559 (95％ CI,0.322～0.743,P＜0.01)、1.297(95％ CI,1.132～1.486,P＜0.01)和0.530(95％ CI,0.421～0.652,P＜0.01) 、0.896(95％ CI,0.775 ～ 1.211,P=0.358)、12.111 (95％CI,9.820 ～ 14.937,P＜0.01);室速HR随LVEF降低而显著增加(与LVEF 0.41 ～ 0.50组相比,LVEF 0.31 ～0.40、0.21 ～0.30和≤0.20组室速HR分别为1.760(95％CI,1.218 ～2.345,P＜0.01)、2.396(95％ CI,2.019～2.783,P＜0.01)和4.209(95％ CI,3.554 ～4.862,P＜0.01),但LVEF各组间室早HR差异无统计学意义.结论 CSHF患者室早和室速的发生率高;室速HR随LVEF减低而增加;不同病因引起的CSHF患者并发室早和室速情况各不相同.     

Suppression of chronic ventricular arrhythmias with propranolol.

The antiarrhythmic efficacy of propranolol was evaluated in 32 patients with chronic high frequency ventricular arrhythmias in a placebo-controlled protocol. After a placebo control period, propranolol was begun and the dosage increased sequentially until arrhythmia suppression was achieved, side effects appeared, or a maximum dosage of 960 mg/day was reached. Computerized analysis of ambulatory recordings was used to quantify the arrhythmias. Twenty-four patients had 70--100% arrhythmia suppression at plasma levels ranging from 12--1100 ng/ml (end of dosing interval). Eight patients in this group had frequent episodes of ventricular tachycardia that were totally suppressed at or below the dosage that produced greater than or equal to 70% suppression of ventricular ectopic depolarizations (VEDs). A biphasic dose-response curve was seen in five patients who responded with a decrease in arrhythmia frequency in the lower ranges of dosages but had increased frequency of ectopic rhythms as the dosage was increased above the optimal level. Only one-third of patients responded at doses less than or equal to 160 mg/day. However, with dosages of 200--640 mg/day, an additional 40% responded. Propranolol appears to control ventricular arrhythmias safely and effectively in many patients. The finding that the antiarrhythmic effect in many patients required plasma concentrations greater than those that produce substantial beta-adrenergic blockage raises a question whether blockade of cardiac beta receptors can directly account for all of the antiarrhythmic actions of propranolol.     

Relation between acute ventricular arrhythmias, ventricular late potentials and mortality in acute myocardial infarction.

The relation between ventricular late potentials and the occurrence of acute (in-hospital) and hyperacute (before hospital admission) ventricular tachycardia or fibrillation was studied in 281 consecutive patients with uninterrupted acute myocardial infarction. The prevalence of late potentials was significantly higher in patients with than without ventricular tachycardia/fibrillation (65 vs 22%; p less than 0.01). These relations persisted among patients with left bundle branch block, although a different definition was used for identifying late potentials in these patients. Multivariate analysis showed that presence of late potentials and peak creatine kinase enzyme level were the only 2 independent variables associated with early ventricular tachycardia/fibrillation. Total in-hospital mortality, as well as in-hospital cardiac mortality, was significantly higher among patients with than without acute ventricular tachycardia/fibrillation. However, at 1 year, mortality rates did not differ between the 2 groups. The following conclusions were drawn from this study: (1) Late potentials are closely related to ventricular tachycardia/fibrillation in hyperacute and acute phases of infarction. (2) Presence of left bundle branch block does not mitigate against the finding of late potentials in these patients. (3) Early ventricular tachycardia/fibrillation in acute infarction is related to large infarctions and to a high in-hospital mortality rate.