Proarrhythmia, cardiac arrest and death in young patients receiving encainide and flecainide. The Pediatric Electrophysiology Group

The potential for proarrhythmic responses to the class IC sodium channel-blocking drugs encainide and flecainide has not been well described in young patients. Therefore, data were retrospectively collected from 36 institutions regarding 579 young patients who were administered encainide or flecainide for treatment of supraventricular tachycardias (encainide 86 patients, flecainide 369 patients) or ventricular arrhythmias (encainide 21 patients, flecainide 103 patients) to assess the frequency of proarrhythmia, cardiac arrest and death during therapy (adverse events). The two drugs were similar in regard to efficacy (flecainide 71.4%, encainide 59.8%) and rate of proarrhythmic responses (flecainide 7.4%; encainide 7.5%). However, patients receiving encainide more frequently experienced cardiac arrest (encainide 7.5% vs. flecainide 2.3%, p less than 0.05) or died during treatment (encainide 7.5% vs. flecainide 2.1%, p less than 0.05). Detailed data were provided for 44 patients experiencing one or more adverse events. Patient age, previous drug trials, concomitant therapy and days of inpatient monitoring were similar for patients receiving encainide or flecainide. However, echocardiographic left ventricular shortening before treatment was lower among patients receiving encainide (0.23 +/- 0.09) than among those receiving flecainide (0.34 +/- 0.06, p less than 0.05). Plasma drug concentrations were rarely elevated. Cardiac arrest (12 patients) and deaths (13 patients) occurred predominantly among patients with underlying heart disease, particularly among patients receiving flecainide for supraventricular tachycardia (8.3% vs. 0.3%, p less than 0.001). Fifteen patients with an ostensibly normal heart and normal ventricular function experienced proarrhythmia during treatment for supraventricular tachycardia, but only 3 of the 15 had a cardiac arrest or died. The relatively high incidence of adverse events should be considered when contemplating treatment with encainide or flecainide, particularly among patients with underlying heart disease.     

Circadian variation in the frequency of sudden cardiac death

To determine whether sudden cardiac death exhibits a circadian rhythm similar to that recently demonstrated for nonfatal myocardial infarction, we analyzed the time of day of sudden cardiac death as indicated by death certificates of 2203 individuals dying out of the hospital in Massachusetts in 1983. The data reveal a prominent circadian variation of sudden cardiac death, with a low incidence during the night and an increased incidence from 7 to 11 A.M. The pattern is remarkably similar to that reported for nonfatal myocardial infarction and episodes of myocardial ischemia. The finding that the frequency of sudden cardiac death is increased in the morning is compatible with hypotheses that sudden cardiac death results from ischemia or from a primary arrhythmic event. Further study of the physiologic changes occurring in the morning may provide new information supporting or refuting these hypotheses, thereby leading to increased understanding and possible prevention of sudden cardiac death.     

Circadian variability in the occurrence of sudden cardiac death in patients with hypertrophic cardiomyopathy

Objectives. The present study examined whether sudden death in patients with hypertrophic cardiomyopathy occurred with a particular pattern of frequency throughout the day.Background. Previous investigators have shown a circadian distribution in the occurrence of sudden death and other cardiovascular events in patients with atherosclerotic coronary artery disease. Sudden death is also an important feature of the natural history of patients with hypertrophic cardiomyopathy.Methods. The study group comprised 94 patients with a time of death (or cardiac arrest) that could be ascertained accurately to the nearest hour. This hourly distribution was analyzed by harmonic regression.Results. Sudden death did not occur uniformly or randomly throughout the day. Rather, it was distributed in a bimodal pattern that conformed to a two-harmonic regression model. A disproportionate number of sudden deaths (43 [46%] of 94) occurred in the first peak in midmorning between 7 amand 1 pm. The second peak of sudden death was less distinct but was in the early evening, between 8 pmand 10 pm. This periodicity in occurnace of sudden cardiac death was not evident for the days of the week or months of the year and, furthermore, did not appear to be influenced by other clinical variables, such as age, gender, severity of symptoms, subaortic gradient or left ventricular wall thickness. Sudden death occurred most commonly during periods of severe exertion (37 [39%] of 94).Conclusions. Sudden death in hypertrophic cardiomyopathy demonstrates a bimodal pattern of circadian variability over the 24-h day, with a prominent midmorning peak similar to that described in patients with coronary artery disease, and a less striking early-evening peak of occurrence. These findings suggest that temporally related physiologic changes, possibly in the electrical vulnerability of the myocardial substrate, may play a role in the sudden death of patients with hypertrophic cardiomyopathy.     

Sudden cardiac death and arrhythmia profile in patients with single-vessel coronary disease

214 patients with single vessel disease (high grade stenosis greater than or equal to 75% or occlusion of the LAD, RCA or LCX) were followed for 1-78 months, average 51 months. Incidence of sudden death was studied in relation to coronary artery lesions, left ventricular wall motion and ventricular arrhythmias found during ambulatory ECG monitoring at the time of angiography. Incidence of sudden death was 11.1% (16/144) in LAD, 7.3% (4/55) in RCA and 6.7% (1/15) in LCX lesions. Coronary artery occlusion was associated with a significantly higher incidence of sudden death (14.6%, 18/123) than high-grade stenosis (3.3%, 3/91) (p less than 0.05). The risk of sudden death increased markedly in patients with complex arrhythmias and an occluded LAD or RCA (21.0%, 8/38; 18.2%, 2/11) compared to patients without complex arrhythmias (14.7%, 5/34; 5.5%, 1/18) (p = ns). Only one patient (1/15, 6.7%) with an isolated LCX lesion died suddenly. Our data show that the incidence of sudden death over 51 months is relatively low in patients with single vessel disease. However, LAD occlusion or RCA lesion with akinetic left ventricular areas and complex arrhythmias are independent predictors of sudden death.     

Mechanism and prediction of sudden cardiac death in arrhythmia patients using electrophysiological studies

Thirty nine cases, in which sudden cardiac death (SCD) was suspected, were studied to evaluate the mechanism and the prediction of SCD in arrhythmia-patients using electrophysiological studies (EPS). The 39 cases (28 male and 11 female) were located by surveying 2098 patients who underwent EPS for the evaluation of arrhythmias. Age at time of EPS ranged from 4 to 86 years, average 50.5 years. Time from EPS to death was 2 to 163 months, average 27.9 months. Underlying heart disease was: dilated cardiomyopathy in 11, old myocardial infarction in 5, ischemic heart disease in 5, hypertensive heart disease in 5, valvular heart disease in 3, hypertrophic cardiomyopathy in 2, arrhythmogenic right ventricular dysplasia in 1, myocarditis in 1, sarcoidosis in 1, cor pulmonale in 1, and no obvious heart disease in 4. Fifteen had a permanent pacemaker implanted. SCD in cases without a permanent pacemaker (24 cases): 2 had chronic complete A-V block (one BH block, one HV block), 1 had advanced A-V block (HV block), 3 had bundle branch block with first degree HV block, 9 had ventricular tachycardia (VT), 3 had sick sinus syndrome (SSS), 3 had paroxysmal atrial flutter, 1 had WPW syndrome and paroxysmal atrial fibrillation, 1 had paroxysmal atrial tachycardia, and 3 had premature ventricular beats and first degree HV block. SCD in cases with permanent pacemaker (15 cases): 5 had SSS, and 10 had A-V block. In 3 of the 5 with SSS and 7 of the 10 with A-V block, VT was found before pacemaker implantation. In our study, brady and tachyarrhythmias coexisted in 25 cases (64%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of encainide in patients with ventricular arrhythmia and poor ventricular function

Gated cardiac scanning was used to evaluate the hemodynamic effects of encainide in 19 patients (1 woman) with complex ventricular arrhythmia and depressed left ventricular (LV) function (ejection fraction less than 45%). Patients were 36 to 80 years old (average 61). All were candidates for long-term encainide therapy after having failed with currently available antiarrhythmics. Sixty-three percent had congestive heart failure before they received encainide. All were evaluated in the hospital before encainide therapy by a gated cardiac scan performed at least 3 days after discontinuing all antiarrhythmic drugs. Patients received oral encainide in doses of 75 to 200 mg. Gated cardiac scans were repeated 1 to 2 weeks later when an 80% reduction in frequency of premature ventricular complexes was observed on a 24-hour Holter recording. No patient had worsening of congestive heart failure during encainide therapy. Encainide did not significantly affect ejection fraction, which averaged 22 +/- 10% before and 25 +/- 14% (SD) after encainide (difference not significant [NS]). Other hemodynamic variables, including heart rate, blood pressure, stroke volume and end-diastolic volume, remained unchanged during encainide therapy. Digoxin blood levels in 10 patients averaged 1.04 +/- 0.43 before and 1.22 +/- 0.47 mg/ml (NS) during encainide therapy. Thus, encainide given orally in clinically effective doses does not appear to have significant hemodynamic effects in patients with ventricular arrhythmia and depressed LV function.     

心力衰竭室性心律失常与心脏性猝死的研究及治疗进展

心力衰竭是各种心脏疾病的终末表现,心力衰竭患者合并室性心律失常是临床上一种常见现象,室性心律失常是心力衰竭患者心脏性猝死的主要原因。通过研究心力衰竭患者室性心律失常发生机制和猝死风险,对患者进行危险分层并实施安全有效的干预措施,对于降低心力衰竭患者的死亡率及改善预后有重要临床意义。     

Determinants of recurrent ventricular arrhythmia or death in 300 consecutive patients with ischemic heart disease who experienced aborted sudden death: data from the Leiden out-of-hospital cardiac arrest study

OBJECTIVE: Evaluation of the relation between clinical characteristics and incidence of recurrent ventricular arrhythmias (VAs) or death during long-term follow-up in a cohort of 300 consecutive ischemic heart disease (IHD) patients who had survived an episode of sudden cardiac arrest (SCA). Background: Survivors of life-threatening VA are at high risk for recurrent events. METHODS: A total of 300 consecutive survivors of SCA with IHD were included in a standardized screening and evaluation protocol. Multivariable Cox regression analysis was performed to determine the relation between clinical variables at baseline and the incidence of recurrent VA, all-cause mortality and the composite of both (composite endpoint). RESULTS: The presenting arrhythmia was VT in 156 (52%) patients and VF in 144 (48%) patients. Revascularization was performed in 78 (26%) patients and an ICD was implanted in 216 (72%) patients. During follow-up (mean 30 +/- 21 months) 37 (12%) patients died and 88 (29%) patients experienced a recurrence. Advanced age (adjusted hazard ratio (HR) 2.0; 1.2-3.3), history of heart failure (HR 1.8; 1.2-2.6), and amiodarone use (HR 3.1; 2.1-4.6) were independent predictors for the composite endpoint. VT as presenting arrhythmia was an independent predictor for all-cause mortality only (HR 2.4; 1.2-4.8). A decreased risk of recurrences was determined by beta-blocker use (HR 0.5; 0.4-0.8) and coronary revascularization (HR 0.3; 0.2-0.6). CONCLUSION: In a cohort of 300 consecutive survivors of SCA the incidence of recurrent VA and death is dependent on patient age, history of heart failure, and use of amiodarone. In contrast, use of beta-blockers and aggressive coronary revascularization improve the outcome.     

Use of rhythmol in patients with cardiac arrhythmia

Twenty-six patients were treated with Rhythmol (Ro 2-5803) during 29 episodes of arrhythmia. The drug was given orally and intravenously. The criterion of effectiveness was conversion to normal sinus rhythm.

Restoration of sinus rhythm occurred in seven episodes of arrhythmia, six of these being acute arrhythmias. The seventh was chronic atrial arrhythmia. Only one of 15 episodes of chronic atrial arrhythmias was converted to sinus rhythm.

Side effects were hypotension in 3 of 17 intravenous trials; gastrointestinal symptoms in 9 of 16 oral trials; and widening of the QRS complex of the electrocardiogram in 4 trials (three oral and one intravenous).

In its present form, this drug has no advantages over the usual agents for the treatment of chronic atrial arrhythmias. Its use by mouth is associated with a forbidding incidence of gastrointestinal reactions.     

Increased risk of death and cardiac arrest from encainide and flecainide in patients after non-Q-wave acute myocardial infarction in the Cardiac Arrhythmia Suppression Trial

This report examines whether in the Cardiac Arrhythmia Suppression Trial death and cardiac arrest from encainide, flecainide and moricizine during the titration phase and from encainide and flecainide during the follow-up phase were related to presence (Q-wave acute myocardial infarction [Q-AMI]) or absence (non-Q-AMI) of pathologic Q waves. In all, 2,371 patients (70% with Q-AMI, 26% with non-Q-AMI, and 4% unknown) entered the titration phase, starting 117 ± 163 days after index AMI and lasting for an average of 21 days. For the titration phase, no significant differences existed between Q-AMI and non-Q-AMI patients for death and cardiac arrest rate, ventricular premature complex suppression rate, and nonrandomization rate. A total of 1,498 patients entered the follow-up phase of an average of 10 months (starting 129 ± 158 days after the index AMI), and were randomized to encainide or flecainide, or their matching placebos. In the placebo group, non-Q-AMI patients had a significantly lower rate of death and cardiac arrest than Q-AMI patients (1.0 and 4.6%, respectively; P = 0.04). Encainide and flecainide significantly elevated death and cardiac arrest rate in both non-Q-AMI patients (8.7%, p < 0.01) and Q-AMI patients (7.8%, P = 0.04). The relative risk for encainide or flecainide over placebo in the non-Q-AMI patients was 8.7, which was significantly higher than 1.7 observed for the Q-AMI patients (p = 0.03). None of the baseline characteristics had any significant interaction with encainide or flecainide.

In conclusion, during the relatively early post-AMI period, therapy with encainide, flecainide or moricizine resulted in similar rates of ventricular premature complex suppression and death/cardiac arrest between non-Q-AMI and Q-AMI groups. In contrast, during the late postmyocardial infarction period, therapy with encainide or flecainide was associated with a much steeper increase in death/cardiac arrest rate in the non-Q-AMI group than in the Q-AMI group.     

Circadian variation of arrhythmia onset patterns in patients with persistent atrial fibrillation

Background

The circadian onset patterns and cycle lengths of atrial tachyarrhythmias (AT) were determined in a group of patients with persistent atrial fibrillation.

Methods

Fifteen patients, mean age 63 ± 14 years and 80% male, were implanted with the Jewel AF atrial defibrillator (Medtronic, Minneapolis, Minn) for persistent atrial fibrillation only. Onset times of AT and median onset atrial cycle lengths were determined from device memory.

Results

Over a follow-up period of 23.3 ± 7 months, 227 episodes of persistent AT were treated by patient-activated atrial defibrillation. The peak onset of persistent AT was nocturnal, with 74% of episodes initiating between 8 pm and 8 am. Eighty-seven percent of the patients experienced an additional 403 paroxysmal AT episodes. These episodes showed a “double-peaked” pattern with the least number of episodes occurring between midnight and 8 am. The mean onset atrial cycle length of persistent AT was significantly shorter than the paroxysmal AT episodes (200 ± 37 ms vs 240 ± 39 ms, P < .005). The atrial cycle lengths at arrhythmia onset of both paroxysmal and persistent AT episodes also demonstrated circadian variation.

Conclusion

There is a circadian distribution of onsets for persistent AT with predominance at night. Patients with persistent AF have >1 type of atrial arrhythmia with differences in the onset patterns and atrial cycle lengths, suggesting different triggers and onset mechanisms.     

Circadian variation in the incidence of sudden cardiac death in the Framingham Heart Study population

To determine if sudden cardiac death shows circadian variation, the time of day of sudden cardiac deaths in the Framingham Heart Study was analyzed. Analysis was based on mortality data collected in a standardized manner for the past 38 years for each death among the 5,209 persons in the original cohort. The necessary assumptions about the cause and timing of unwitnessed deaths were made in a manner likely to diminish the possibility of detecting an increased incidence of sudden cardiac death during the morning. In the Framingham study, analyses using these assumptions reveal a significant circadian variation (p less than 0.01) in occurrence of sudden cardiac death (n = 429), with a peak incidence from 7 to 9 AM and a decreased incidence from 9 AM to 1 PM. Risk of sudden cardiac death was at least 70% higher during the peak period than was the average risk during other times of the day. Further studies are needed to confirm this finding in other populations, to collect data regarding medications and to determine activity immediately before sudden cardiac death. Investigation of physiologic changes occurring during the period of increased incidence of sudden cardiac death may provide increased insight into its causes and suggest possible means of prevention.     

Prevalence of early repolarization pattern and its association with sudden cardiac death and arrhythmia over one-year follow-up in an Egyptian cohort

Background and objectives

Early repolarization pattern (ERP) is not uncommon electrocardiography (ECG) finding and could be associated with arrhythmia and sudden cardiac death (SCD). We aimed to prospectively determine the prevalence of ERP and its association with arrhythmia and SCD during one-year follow-up in an outpatient Egyptian cohort.