Frequent Ventricular Premature Depolarizations Research Articles

Electrocardiographic features of the presence of occult myocardial disease in patients with VPD-induced cardiomyopathy.

BackgroundFrequent ventricular premature depolarizations (VPDs) can cause reversible cardiomyopathy (CMP). However, many patients maintain a normal left ventricular (LV) function with a high VPD burden. The electrocardiographic characteristics of VPD‐induced CMP have not been elucidated.MethodsOne hundred and eighty (91 men, age; 51 ± 15 years) patients with frequent idiopathic VPDs (>10% VPDs/day or >10 000 VPDs/day) were studied. All patients underwent successful ablation and were then divided into two groups according to the echocardiographic findings before and after the ablation procedure.ResultsGroup A (n = 139) had a normal LV function with VPD frequencies, and Group B (n = 41) had reversible LV dysfunction after ablation. The VPD QRS duration (QRSd) was wider in patients with CMP (Group A vs Group B; 137.2 ± 12.0 milliseconds vs 159.7 ± 5.3 milliseconds, P < .001). VPDs with a terminal QRS delay marked by a notch followed by a discrete lower amplitude signal after the peak R wave in any precordial lead were identified. The incidence of terminal signals was higher in the CMP group (Group A vs Group B; 2.1% vs 53.6%, P < .001).ConclusionsThe wider VPD QRSd and terminal QRS delay in patients with VPD‐induced CMP suggest subclinical cell‐to‐cell conduction abnormalities as a potential factor predisposing VPD‐induced CMP.

Accuracy of smartphone-based ECG for the diagnosis of various cardiac arrhythmias

Diagnosis of cardiac arrhythmias can be challenging due to their frequent transient nature. Smartphone-based ECG has previously been studied for atrial fibrillation (AF) diagnosis. However, data is lacking regarding diagnostic accuracy of smartphone-based ECGs for other frequent arrhythmias. To assess the accuracy of Alivecor smartphone-based ECG (AECG) device for the diagnosis of various bradyarrhythmias or tachyarrhythmias. Hospitalized patients were eligible for inclusion if they had any of the following arrhythmias: AF, atrial tachycardia/flutter (AT), sinus rhythm with frequent atrial premature depolarizations (APD), sinus rhythm with frequent ventricular premature depolarizations (VPD), sinus tachycardia > 120 beats/min, sinus bradycardia < 40 beats/min, high-degree atrioventricular (AV) block, atrioventricular node reentrant tachycardia (AVNRT) and ventricular tachycardia (VT). Reference twelve-lead ECG were recorded, and the corresponding one-lead AECG was independently interpreted by four blinded electrophysiologists. Seventy-three patients (57 men; aged 72 ± 14 years) were included. For the diagnosis of bradyarrhythmias, AECG had a sensitivity and specificity of 75%–95% for sinus bradycardia, and 52%–98% for AV block. For atrial tachyarrhythmias, sensitivites and specificites were good for APD (83%–97%), AF (82%–87%), and sinus tachycardia (86%–98%), whereas sensitivity was poor for AT (49%–93%) and AVNRT (10%–99%), with very frequent confusion between them. For ventricular tachyarrhythmias, sensitivities and specificities were 70%–95% for VPD, and 89%–100% for VT ( Table 1 , Fig. 1 ). AECG is accurate for the diagnosis of sinus bradycardia, sinus tachycardia, APD, VPD, AF and VT. However, AV block, AT and AVNRT were poorly diagnosed by AECG, with a low sensitivity and very frequent confusion between AT and AVRNT.

Recovery of renal dysfunction after catheter ablation of outflow tract ventricular arrhythmias in patients with ventricular premature depolarization-mediated cardiomyopathy.

Frequent ventricular premature depolarizations (VPDs) may cause cardiomyopathy (VPDCM), which often improves after VPD suppression. This study aimed to evaluate whether ablation of outflow tract ventricular arrhythmias (OT VAs) in patients with VPDCM improves renal in addition to left ventricular (LV) function. We retrospectively evaluated 153 patients with OT VAs and examined VPD burden and LV ejection fraction (LVEF), as well as estimated glomerular filtration rate (eGFR) pre- and post-ablation. LV dysfunction was defined as LVEF <50% and impaired renal function was defined as eGFR of <60mL/min/1.73m2. Fifty-five patients had VPDCM. During mean follow-up of 14months, 140 (92%) were free from arrhythmia. In patients with VPDCM, patients with baseline LVEF 40-50% had greater improvement in the post-ablation LVEF compared to patients with baseline LVEF <40% (p < 0.01). At baseline, 36 (72%) patients had renal dysfunction, 29 (81%) of whom had improvement in eGFR from baseline after successful ablation from eGFR 51 to 57mL/min/1.73m2. There was a significant association between cardiac (ΔLVEF ≥10%) and renal (ΔeGFR ≥10%) improvement (r = 0.54, p = 0.04). Using logistic regression analysis, procedural success was an independent predictor of improvement of cardiac (odds ratio [OR] = 13.7, p = 0.03) and renal function (OR = 21.0, p = 0.047). Successful catheter ablation of OT VA reduces VPD burden and is associated with improved cardiac and renal function in patients with VPDCM.

Ventricular premature depolarization QRS duration as a new marker of risk for the development of ventricular premature depolarization–induced cardiomyopathy

Frequent ventricular premature depolarizations (VPDs) can cause cardiomyopathy (CMP). The mechanisms underlying its development remain unclear, with VPD burden being only a weak predictor of risk. To determine whether VPD QRS duration at the time of initial presentation could predict risk for the subsequent development of CMP in patients with normal left ventricular ejection fraction (LVEF). From consecutive patients referred for ablation between January 1, 2006, and April 2, 2013, with ≥10% VPDs on 24-hour Holter monitoring, we identified 45 patients with normal LVEF and an electrocardiogram of the targeted VPD, who were then followed for at least 6 months (median 14 months; interquartile range [IQR] 8-32 months) before intervention. We excluded patients with structural or genetic heart disease. Of the 45 patients, 28 (62%) maintained normal LVEF and 17(38%) developed VPD-induced CMP. VPD burden was similar (26.5% [IQR 19.3%-39.5%] vs 26.0% [IQR 16.4%-41.0%]; P = 0.4) between the 2 groups. Patients who developed VPD-induced CMP had significantly longer VPD QRS duration (159 ms vs 142 ms; P < .001) and a longer sinus QRS duration (97 ms vs 89 ms; P = .04). A VPD QRS duration of ≥153 ms best predicted development of VPD CMP (82% sensitivity and 75% specificity). Longer VPD QRS duration and a non-outflow tract site of VPD origin were independent risk factors for left ventricular dysfunction after multivariate analysis. VPD QRS duration longer than 153 ms and a non-outflow tract site of origin might be useful predictors of the subsequent development of VPD-induced CMP.

Predictors of recovery of left ventricular dysfunction after ablation of frequent ventricular premature depolarizations

Frequent ventricular premature depolarizations (VPDs) can cause reversible left ventricular (LV) dysfunction. However, not all patients normalize their LV function after VPD elimination. To evaluate predictors of recovery of LV function following the elimination of frequent VPDs. We identified patients with ≥10% VPDs/24 h and an LV ejection fraction of <50% who underwent successful ablation between 2007 and 2011. Subjects were classified as having reversible (≥10% increase to a final LV ejection fraction of ≥50%) or irreversible (≤10% increase or final LV ejection fraction <50%) LV dysfunction on the basis of echocardiographic follow-up. A reference group with ≥10% VPDs but normal LV function was identified. One hundred fourteen patients with ≥10% VPDs were identified; 66 had preserved and 48 had impaired LV function. Over a median follow-up of 10.6 months, 24 of 48 were classified as reversible and 13 of 48 as irreversible and 11 of 44 were excluded. There was a gradient of VPD QRS duration between the control, reversible, and irreversible groups (mean VPD QRS 135, 158, and 173 ms, respectively; P < .001). This gradient persisted even for the same site of origin. In multivariate analysis, the only independent predictor of irreversible LV function was VPD QRS duration (odds ratio 5.07 [95% confidence interval 1.22-21.01] per 10-ms increase). In patients with LV dysfunction and frequent VPDs, we identified VPD QRS duration as the only independent predictor for the recovery of LV function after ablation. This suggests that VPD QRS duration may be a marker for the severity of underlying substrate abnormality.

Reversal of outflow tract ventricular premature depolarization–induced cardiomyopathy with ablation: Effect of residual arrhythmia burden and preexisting cardiomyopathy on outcome

Outflow tract ventricular premature depolarizations (VPDs) can be associated with reversible left ventricular cardiomyopathy (LVCM). Limited data exist regarding the outcome after ablation of outflow tract VPDs from the LV and the impact of residual VPDs or preexisting LVCM prior to the diagnosis of VPDs on recovery of LV function. To examine the safety, efficacy, and long-term effect of radiofrequency ablation on LV function in patients with LVCM and frequent outflow tract VPDs and examine the effect of ablation in patients with LVCM known to precede the onset of VPDs and the impact of residual VPD frequency on recovery of LV function. Sixty-nine patients (43 men; age 51 ± 16 years) with nonischemic LVCM (left ventricular ejection fraction [LVEF] 35% ± 9%, left ventricular diastolic diameter [LVDD] 5.8 ± 0.7 cm) were referred for ablation of frequent outflow tract VPDs (29% ± 13%). VPDs originated in the right ventricular outflow tract in 27 (39%) patients and the left ventricular outflow tract in 42 (61%) patients. After follow-up of 11 ± 6 months, 44 (66%) patients had rare (<2%) VPDs, 15 (22%) had decreased VPD burden (>80% reduction and always <5000 VPDs), and 8 (12%) had no clinical improvement with persistent (5 patients) or recurrent (3 patients) VPDs. Only patients with either rare or decreased VPD burden had a significant improvement in LVEF (ΔLVEF 14% ± 9% vs 13% ± 7% vs -3% ± 6%, respectively, P <.001) and LVDD (ΔLVDD -4 ± 5 vs -2 ± 4 vs 0 ± 4, respectively, P = .038), regardless of chamber of origin. The magnitude of LVEF improvement correlated with the decline in residual VPD burden (r = 0.475, P = .007). Patients with preexisting LVCM had a more modest but still significant improvement in LV function compared to patients without preexisting LVCM (ΔLVEF 8% vs 13%, P = .046). Multivariate analysis revealed ablation outcome, higher LVEF, and absence of preexisting LVCM were independently associated with LVEF improvement. Frequent outflow tract VPDs are associated with LVCM regardless of ventricle of origin. Significant (>80%) reduction in VPD burden has comparable improvement in LV function to complete VPD elimination. Successful VPD ablation may be beneficial even in patients with preexisting LVCM.

Angina and its treatment.

Angina and its treatment.

Correction - Amiodarone reduced ventricular fibrillation or arrhythmic death in MI with frequent ventricular premature depolarizations

Correction - Amiodarone reduced ventricular fibrillation or arrhythmic death in MI with frequent ventricular premature depolarizations

Amiodarone reduced ventricular fibrillation or arrhythmic death in MI with frequent ventricular premature depolarizations

Source Citation Cairns JA, Connolly SJ, Roberts R, Gent M, for the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators. Randomised trial of outcome after myocardial infarction ...

Relation of Circadian Ventricular Ectopic Activity to Cardiac Mortality

The relation between the circadian occurrence of ventricular premature depolarizations (VPD) and sudden arrhythmic death was examined in a subset of patients entered into the Cardiac Arrhythmia Suppression Trial (CAST). Ambulatory electrocardiographic recordings with hourly measurement of VPD frequency were available in 357 patients. Forty percent of the patients (142 of 357) demonstrated circadian variation in VPD frequency between 6:00 a.m. and 9:59 a.m. that was significantly higher (p <0.05) than what could randomly be expected from an overall 24-hour average for that patient. The only baseline characteristics in patients with circadian VPDs were age (p <0.04), history of cardiac arrest (p <0.01), presence of higher frequency of VPDs (p <0.002), more frequent episodes of ventricular tachycardia (p <0.04), and more frequent episodes of slow runs (p <0.04). There was no difference in mortality in patients with or without circadian VPD variation; drug treatment did not effect mortality. These data indicate that the presence of circadian VPDs is not a predictor of sudden arrhythmic death in patients with a high frequency of VPDs. (Am J Cardiol 1996;78:881–885)

Prognostic importance of the length of ventricular tachycardia in patients with nonischemic congestive heart failure

In patients with congestive heart failure the frequency of ventricular arrhythmias poorly predicts mortality. It is unknown whether the length of ventricular tachycardia is a better predictor of mortality in these patients. We therefore investigated the prognostic importance of the length of the longest run of ventricular tachycardia, the frequency of ventricular tachycardia, and the frequency of ventricular premature depolarizations with 24-hour ambulatory electrocardiographic recordings in 122 patients with heart failure. We also determined whether the cause of heart failure affects the prognostic importance of these parameters. Each ambulatory electrocardiographic recording was evaluated for the frequency of ventricular premature depolarizations and ventricular tachycardia and for the length of the longest run of ventricular tachycardia. For each electrocardiographic parameter patients were divided into groups based on the median value of that parameter. Mortality among groups was compared in all patients and then separately for nonischemic and ischemic patients. Neither the frequency of ventricular premature depolarizations nor the frequency of ventricular tachycardia predicted mortality whether or not cause was considered. When all patients were examined, the length of ventricular tachycardia did predict an increased risk of death. However, when cause was considered, length of ventricular tachycardia predicted mortality only in the nonischemic patients and not in the ischemic patients. We conclude that the length of ventricular tachycardia may be the best electrocardiographic predictor of mortality in patients with nonischemic heart failure.

901-62 Effects of Intraventricular Conduction Delay on Survival in Patients Taking Antiarrhythmic Drugs

An intraventricular conduction delay (IVCD) may influence the efficacy and safety of antiarrhythmic (AA) drugs. The Cardiac Arrhythmia Suppression Trial (CAST) allows assessment of the influence of an IVCD on survival when AA drugs are used following a myocardial infarction IMI). In CAST, MI patients with frequent ventricular premature depolarization (VPDs) (averaging 28 VPD/H) were randomized to receive an AA drug (flecainide, encainide or moricizine) or a placebo. After therapy was started 956 patients (35%) had an IVCD (QRS ≥ 0.11 sec) and 1796 patients (65%) had a QRS &lt; 0.11 sec. Patients IVCD patients differed from those with normal conduction by: being older (72% &gt; age 60 vs. 54%); more often having an ejection fraction &lt; 0.30 130% vs. 21%); more often having &gt;50 VPD/H at baseline (51% vs. 43%): and having more pre-CAST Mis (45% vs. 38%) (P &lt; 0.001 for each). Mean follow-up was 1.1 years. GRS Duration &lt;0.11 sec ≥0.11 sec Mortality rate (% per year) AA drug 7.3% 16.7% Placebo 6.0% 7.8% Arrhythmic death rate (% per year) AA drug 4.4% 10.9% Placebo 3.6% 4.4% After adjusting for age, ejection fraction and prior MI, the combination of IVCD and antiarrhythmic drug remains a significant predictor of increased mortality (hazard ratio 1.69, P &lt; 0.04) Antiarrhythmic drug use is associated with and possibly a cause of increased mortality and arrhythmic deaths in patients with an IVCD.

Effects of intravenous magnesium sulfate on arrhythmias in patients with congestive heart failure

Intravenous magnesium is an effective treatment for ventricular tachycardia of some etiologies, and in patients with congestive heart failure low serum magnesium concentrations are associated with frequent arrhythmias and high mortality. This suggests that magnesium administration may decrease the frequency of ventricular arrhythmias in patients with heart failure. We therefore assessed the impact of an intravenous magnesium infusion upon the frequency of ventricular premature depolarizations in 40 patients with New York Heart Association (NYHA) class II to IV heart failure and serum magnesium ≤ 2.0 mg/dl. Within 1 week of a baseline 6-hour ambulatory electrocardiographic recording, an infusion of 0.2 mEq/kg of MgSO 4 was given over 1 hour and a repeat 6-hour recording was obtained. There was an inverse relationship between the change in magnesium concentration and the change in frequency of premature ventricular depolarizations; premature ventricular depolarizations declined by 134 ± 207 hr −1 in patients in whom serum magnesium concentration increased ≥ 0.75 mg/dl, but increased by 72 ± 393 hr −1 in patients with a change < 0.75 mg/dl ( p < 0.053). For all patients, the frequency of premature ventricular depolarizations was 283 ± 340 hr −1 pretreatment and 220 ± 269 hr −1 following magnesium infusion ( p = 0.21). Patients with ≥ 300 premature ventricular depolarizations hr −1 demonstrated a decrease from 794 ± 309 to 369 ± 223 hr −1 ( p < 0.001). Intravenous magnesium administration decreased the frequency of couplets from 233 ± 505 to 84 ± 140 ( p < 0.05). We conclude that an acute elevation of serum magnesium concentration following intravenous magnesium administration decreases the frequency of ventricular arrhythmias in patients with congestive heart failure, but the effects of oral supplements need further evaluation.

Loss of efficacy during long-term cifenline therapy: development of antiarrhythmic resistance?

To describe the possible development of antiarrhythmic resistance to cifenline, an investigational Class I agent. Forty patients with chronic ventricular premature depolarizations (VPDs) underwent dose-ranging studies with cifenline, an investigational Class I antiarrhythmic agent. Patients had a minimum of 30 VPDs/h detected by ambulatory electrocardiographic (ECG) monitoring over a 48-hour baseline placebo lead-in period. Twenty-two patients (55 percent) who initially responded received long-term cifenline therapy. Ambulatory ECG monitoring over 24 hours was repeated during active cifenline therapy at three-month intervals and during placebo reintroduction at six-month intervals. After an average follow-up of 28 months, VPD frequency during cifenline therapy was similar to that during initial baseline placebo therapy in 8 of the 22 patients (36 percent) who initially responded. Placebo reintroduction following cifenline failure showed a VPD frequency similar to that with active therapy. All patients had further cifenline dosage increases without success. Plasma cifenline concentrations increased in all patients and were in the high therapeutic range. All 8 patients were switched to other Class I antiarrhythmic agents with successful VPD suppression during treatment with the first alternative drug. We conclude that antiarrhythmic resistance occurred with cifenline in these patients as (1) initial efficacy was established for a minimum of two years, (2) VPD frequency was similar during cifenline therapy and placebo reintroduction, (3) cifenline therapy failure continued despite further dosage titration, and (4) alternative Class I antiarrhythmic therapy was successful in all patients. Repeat intermittent ambulatory ECG monitoring is necessary not only to assess the continued need for antiarrhythmic drug therapy, but also to establish continued long-term efficacy.

Prognostic significance of ventricular premature depolarizations measured 1 year after myocardial infraction in patient with early postinfarction asymptomatic ventricular arrhythmia

Objectives. The objective of this study was to examine the relation between death and the frequency of premature ventricular depolarizations measured approximately 1 year after myocardial infarction.Background. The reported association between premature ventricular depolarizations and death in the weeks after myocardial infarction is in part the basis for the use of antiarrhythmic drugs. Such an association has not been reported on for observations obtained at a much greater interval after myocardial infarction.Methods. We examined the association between mortality and premature ventricular depolarization rates measured 1 year after myocardial infarction in patients with asymptomatic ventricular arrhythmia early (between 6 and 90 days, median 28) after infarction, as measured by 24-h ambulatory electrocardiographic recording. The study group consisted of 502 patients enrolled in the Cardiac Arrhythmia Pilot Study during 1983 to 1985. They were followed up during the course of the study and subsequently by a National Death Index search (average follow-up interval 1,080 days).Results. Death was recorded for 87 patients through 1987. Because patients were admitted to the Cardiac Arrhythmia Pilot Study only if they had ≥10 ventricular premature depolarizations/h, the arrhythmia rate measured at baseline (that is, early after infarction) was not expected to, and did not, predict mortality. In 360 patients ventricular premature depolarization rates were measured approximately 1 year from their index myocardial infarction while they were not receiving antiarrhythmic therapy. In these patients, who had survived 1 year after the index infarction, the rate of ventricular premature depolarizations/h measured 1 year after infarction was highly predictive of subsequent death (p < 0.001). Recent heart failure and a history of diabetes mellitus were also strongly predictive of death.Conclusion. The prognostic value of ventricular premature depolarizations observed 1 year after a myocardial infarction may be significant even in a sample selected for frequent ventricular premature depolarizations observed early after the event.

Moricizine: pharmacodynamic, pharmacokinetic, and therapeutic profile of a new antiarrhythmic.

Moricizine (Ethmozine) is a phenothiazine derivative recently approved in the United States for the treatment of malignant ventricular arrhythmias. Moricizine closely resembles group IA antiarrhythmic agents in the intensity of its effect on the sodium channel, but it differs from the IA subclass in that it shortens the action potential duration in ventricular tissue. Moricizine suppresses frequent ventricular premature depolarizations and nonsustained ventricular tachycardia in 60% to 70% of patients, and it suppresses induced ventricular tachycardia in 15% to 25% of patients. It is well tolerated, with a low incidence of adverse effects. The suggested dosage is 600 to 900 mg per day in three divided doses. Treatment of arrhythmias with prognostic significance should be initiated in the hospital, and monitored with electrophysiologic studies. Additional clinical experience is needed to better define moricizine's role in antiarrhythmic therapy.

Post-myocardial infarction mortality in patients with ventricular premature depolarizations. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Pilot Study.

Among survivors of acute myocardial infarction, frequent and repetitive ventricular premature depolarizations (VPDs) detected on ambulatory monitoring contribute independently to the risk of all-cause mortality and sudden death. Apart from the beta-blockers, no antiarrhythmic drug has been reliably demonstrated to reduce mortality among patients with VPDs. A pilot study was undertaken to gather data to aid in the design of a multicenter trial of amiodarone for the reduction of mortality from cardiac arrhythmias in such patients. Seventy-seven patients with acute myocardial infarction within the previous 6-30 days and 10 or more VPDs/hr or one or more runs of ventricular tachycardia on 24-hour electrocardiographic recording were randomized in a double-blind fashion in a 2:1 amiodarone-to-placebo ratio. The loading dose was 10 mg/kg/day for 3 weeks. The maintenance dose was 300-400 mg/day with reductions at 4-month intervals in response to VPD suppression, excessive plasma levels, or toxicity. VPD suppression at 1 week and 2 weeks was 63% and 85%, respectively, on amiodarone and 17% and 27%, respectively, on placebo. Apart from thyroid-stimulating hormone elevation and skin reactions, no side effects occurred more frequently with amiodarone. The study drug was stopped for side effects or noncompliance in 35% of amiodarone patients and 34% of placebo patients. Patients were followed for a maximum of 2 years (mean, 20 months). Arrhythmic death or resuscitated ventricular fibrillation occurred in two of 48 amiodarone patients (6%) and four of 29 placebo patients (14%), whereas the rates of all-cause mortality were five of 48 (10%) and six of 29 (21%), respectively. Amiodarone, in moderate loading and maintenance dosages with adjustments in response to plasma levels, VPD suppression, and side effects, results in effective VPD suppression and acceptable levels of toxicity.

Avoiding interpretive pitfalls when assessing arrhythmia suppression after myocardial infarction: Insights from the long-term observations of the placebo-treated patients in the Cardiac Arrhythmia Pilot Study (CAPS)

The Cardiac Arrhythmia Pilot Study (CAPS) was a 1 year trial that analyzed the safety and effectiveness of arrhythmia suppression in 502 patients surviving acute myocardial infarction who had ≥10 ventricular premature depolarizations/h or ≥5 runs of ventricular tachycardia on a Holter recording obtained 6 to 60 days after the acute infarction. Because 100 of these patients received placebo in a double-blind fashion for 1 year, a comprehensive objective analysis was performed of spontaneous arrhythmia changes based on real data rather than statistical estimates.In the CAPS placebo group, 19% developed some serious clinical event in 1 year (death, heart failure, proarrhythmia) that could likely be attributable to antiarrhythmic drug toxicity. A significant reduction in the frequency of ventricular premature depolarizations (p = 0.004) occurred in the first few weeks of “therapy,” with a further significant (p < 0.04) decrease between 3 to 12 months. After initiation of placebo antiarrhythmic therapy, 27% had “apparent ventricular premature depolarization suppression” (70% reduction) after one Holter recording evaluation and nearly half (48%) after six Holter recordings to assess suppression were performed.It is concluded that 1) setting a higher percent suppression goal or obtaining multiple baseline Holter recordings decreases the chance of mistaking suppression for spontaneous variability: 2) obtaining frequent individual Holter recordings over the course of drug therapy actually increases the chance of sampling during one extreme variability period, the result of which is to incorrectly infer “suppression” or “proarrhythmia”: and 3) runs of ventricular tachycardia occur in the CAPS study group infrequently, are of low density and exhibit extreme variability such that a primary suppression goal focused on runs of ventricular tachycardia is not a reliable end point for assessing antiarrhythmic therapy.

The Diurnal Variability of Ventricular Premature Depolarizations: Influence of Heart Rate, Sleep, and Wakefulness

The relationships between ventricular premature depolarizations (VPDs) and heart rate (HR) were determined in 14 patients with ventricular arrhythmias and the influence of these relationships on the diurnal variability of ventricular arrhythmias was evaluated. The influence of sleep state, wakefulness, and level of activity on the frequency of VPDs was also studied. Subjects completed 48-72 h of ambulatory electrocardiographic monitoring and nocturnal sleep recordings. Plots of VPD frequency vs. HR were examined and subjects were categorized as HR-dependent if they manifested log-linear increase in VPDs with increasing HR and as HR-independent if no relation between VPD frequency and HR was detected. Sleep suppression of VPDs was observed in the HR-dependent group (p less than 0.05). The reduction in VPD frequency correlated with the reduction in HR and was independent of sleep state or wakefulness. No change in VPD frequency was observed during wakefulness, rapid eye movement sleep, or non-rapid-eye-movement sleep in the HR-independent group. The influence of level of activity on ventricular arrhythmia frequency was also assessed in seven subjects. Any decreases in VPD frequency observed during inactivity were associated with a decrease in HR. These observations suggest that HR is a major determinant of the diurnal variation of VPD frequency in a subset of patients with frequent VPDs.

Long-term efficacy of oral pirmenol in suppressing ventricular premature depolarizations

Pirmenol is an investigational type 1A antiarrhythmic drug the long-term efficacy of which has not been fully determined. Therefore the long-term efficacy of oral pirmenol in supprossing ventricular premature depolarizations (VPDs) was assessed in an open-label, dose-titration study. Twelve patients (eight men and four women; mean age 57 ± 12 years) were treated for 24 to 36 months (mean 33 ± 4). Seven had structural heart disease (three valvular heart disease, two ischemic heart disease, and two hypertensive heart disease) and five did not. The mean left ventricular ejection fraction was 0.63 ± 0.13. Exclusion criteria included <30 VPDs/hr, >15 beats of ventricular tachycardia (VT), or prior failure of more than two antiarrhythmic drugs. Drug efficacy was assessed by 24-hour ambulatory ECG monitoring performed every 3 months during the first year, every 4 months during the second year, and at 6-month intervals during the third year. The mean hourly frequency of VPDs during the placebo phase was 732 ± 608. Seven patients (58%) were treated successfully with effective (>75%) long-term suppression of VPDs. Two patients (17%) had a partial response with effective suppression of VPDs for the first 16 months and 5 months of treatment, respectively. Three patients falled to show consistent suppression of VPDs while receiving pirmenol. The daily dose of pirmenol ranged from 200 to 500 mg (mean 317 ± 94 mg at the beginning of the study and 375 ± 97 mg at the end). No proarrhythmic effects were identified during long-term treatment, and none of the patients withdrew from the study prematurely. Mild side effects included dry mouth, bad taste, and urinary hesitancy. We conclude that oral pirmenol maintains effective long-term suppression of VPDs in approximately 60% of patients and is well tolerated during chronic administration. No proarrhythmic effects occurred during long-term treatment.