Frequent Ventricular Premature Beats Research Articles

Caffeine restriction has no role in the management of patients with symptomatic idiopathic ventricular premature beats.

To assess the role of caffeine restriction in the management of patients with symptomatic idiopathic ventricular premature beats. A randomised, double blind, 6 week intervention trial incorporating dietary caffeine restriction, caffeinated coffee, and decaffeinated coffee. Cardiac outpatient clinic. 13 patients with symptomatic frequent idiopathic ventricular premature beats. Weekly measures of serum caffeine concentration, coffee consumption, visual analogue score of palpitations, and 24 hour ventricular premature beat frequency. The interventions achieved significant alterations in serum caffeine concentrations (P < 0.001) which correlated with coffee consumption (r = 0.70; P < 0.001). Visual analogue palpitation scores showed a small, but significant correlation with ventricular premature beat frequencies (r = 0.34; P = 0.003). However, there were no significant changes in palpitation scores or ventricular premature beat frequencies during the intervention weeks and no significant correlations were found between these variables and serum caffeine concentrations. Caffeine restriction has no role in the management of patients referred with symptomatic idiopathic ventricular premature beats.

A randomized clinical trial of the noninvasive and invasive approaches to drug therapy for ventricular tachycardia: Long-term follow-up of the calgary trial

Individualized antiarrhythmic drug therapy for patients with ventricular tachyarrhythmias may be selected by the noninvasive approach (suppression of spontaneous ventricular premature beats) or the invasive approach (suppression of ventricular tachyarrhythmias induced at an electrophysiologic study). There is controversy over which approach is superior. From a screened population of 124 patients with symptomatic ventricular tachycardia or ventricular fibrillation, 57 patients with both frequent ventricular premature beats and inducible ventricular tachycardia at baseline were randomized to have chronic therapy selected by either the noninvasive or invasive approach. These patients have now been followed up for a minimum event-free period of 6.5 years. By intention-to-treat, therapy selected by the invasive approach prevented subsequent ventricular tachyarrhythmias better than that selected by the noninvasive approach (6-year probabilities of freedom from symptomatic sustained ventricular tachyarrhythmia recurrence; noninvasive approach, 0.45 ± 0.10; invasive approach, 0.73 ± 0.09; P = .02). This advantage of the invasive approach was also evident for the outcome of any ventricular tachyarrhythmia recurrence and for efficacy analyses involving only those patients with a drug-efficacy prediction. We hypothesize that the difference between these results and those of the ESVEM trial are caused, in part, by differences in the characteristics of the enrolled patients and differences in criteria used to define a predicted-effective therapy.

Electrophysiologic and proarrhythmic effects of intravenous inotropic agents

Intravenous inotropic agents promote increased myocardial contractility via elevation of myocyte calcium concentrations, a mechanism that is also known to promote the development of cardiac arrhythmias. The purpose of this article is to review the electrophysiologic effects and relative potential for proarrhythmia associated with dobutamine, dopamine, and the phosphodiesterase inhibitors amrinone and milrinone. Dobutamine increases sinoatrial node automaticity and decreases atrial and atrioventricular (AV) node refractoriness and AV nodal conduction time. The drug also decreases ventricular refractoriness in both healthy and ischemic myocardium. Dobutamine has been shown to increase heart rate in a dose-related fashion in animals and in humans. In humans, dobutamine has been reported to induce ventricular ectopic activity (VEA) in 3% to 15% of patients, although VEAs are often asymptomatic, requiring no intervention. Ventricular tachycardia (VT) associated with dobutamine appears to occur rarely. Patients with underlying arrhythmias or heart failure or those receiving excessive doses of dobutamine are at greatest risk for proarrhythmia. Dopamine increases automaticity in Purkinje fibers and has a biphasic effect on action potential duration. Dopamine has been reported to induce atrial or ventricular arrhythmias in animals. In humans, dopamine may be associated with dose-related sinus tachycardia but has also been reported to cause VEA, which is usually asymptomatic. Dopamine-associated VT appears to occur rarely. Dopamine produces greater elevations in heart rate or frequency of ventricular premature beats at a given value of cardiac index than does dobutamine. The phosphodiesterase inhibitors amrinone and milrinone increase conduction through the AV node and decrease atrial refractoriness. Intravenous administration of these drugs may result in sinus tachycardia in some patients and has been reported to cause VEA, which is often asymptomatic, in up to 17% of patients. VT has also been reported in association with short-term use of intravenous phosphodiesterase inhibitors. In summary, intravenous inotropic agents may be associated with proarrhythmic effects in some patients. The primary arrhythmias reported are sinus tachycardia and VEA, although other supraventricular or ventricular arrhythmias have been reported less commonly. However, clinically significant proarrhythmic effects associated with these agents appear to occur rarely, and, at conventional doses, intravenous inotropic agents are relatively safe with respect to proarrhythmic effects.

Arrhythmias in Centenarians

Many studies have shown an increase in the prevalence of arrhythmias with advancing age. However, little is known about arrhythmias in centenarians. Thirty-two Japanese centenarians aged 100-106 years (14 males, 18 females) were studied. All of them had 12-lead ECGs, and 22 also had 24-hour ambulatory monitoring. As controls, 89 healthy Japanese elderly from the same geographic area underwent 12-lead ECG. Their mean age was 75 +/- 6 years with a range of 63-93 years, and there were 28 males and 61 females. Twenty-three of them also had Holter ECGs. On the 12-lead ECG, the heart rate was slightly, but significantly, higher in the centenarians (76.8 +/- 12.7 beats/min) than that in the elderly subjects (74.9 +/- 5.9 beats/min, P < 0.005). PQ and QTc were significantly longer in the centenarians (174 +/- 29 and 439 +/- 33 msec, respectively) compared with the elderly subjects (158 +/- 23 and 417 +/- 31 msec, P < 0.005 and P < 0.001, respectively). Supraventricular premature beats (SVPBs) were observed in 31% of the centenarians and in 4% of the elderly subjects (P < 0.001). First- and second-degree AV block was recorded in 25% of the centenarians and 1% of the elderly subjects (P < 0.001). Right bundle branch block was found in 19% of the centenarians and 7% of the elderly subjects (P < 0.05). There were no differences in the frequency of ventricular premature beats (VPBs) or QRS voltage. On the Holter ECG, there were no significant differences in average heart rate, maximum heart rate, minimum heart rate, or the longest RR interval. A subgroup of centenarians had frequent SVPBs. However, none of them had > 1,000 VPBs/day as opposed to four elderly subjects (P < 0.01). Atrial fibrillation was not observed in any records of the centenarians despite the presence of frequent SVPBs. These data suggest that conduction disturbances of the AV nodal--His-Purkinje system and frequent SVPBs are common in centenarians, whereas very frequent VPBs and atrial fibrillation seem less common.

Prolonged monitoring for detection of symptomatic arrhythmias after slow pathway ablation in AV-nodal tachycardia

To study the incidence of symptoms and recurrences of AV-nodal re-entrant tachycardia (AVNT) after treatment with radio-frequency ablation of the slow pathway, event recording with transtelephonic transmission was performed for at least 3 weeks in 19 patients out of a series of 25. Follow-up with an implanted antitachycardia device was possible in two other patients, making the total number under continued surveillance 21 25 . The period of monitoring was prolonged as complaints remained or became present after 1 month in eight patients. During a mean follow-up of 10 months, late recurrence of AVNT was observed in this way in 4 25 patients; they were submitted to a second procedure. Symptoms were present in many others and were explained by the recordings. Sinus tachycardia was recorded in three patients, intermittent AV-block of the first degree in another, and frequent atrial or ventricular premature beats in six patients. These minor arrhythmias tended to decrease over time. A coexistent atrial tachycardia was redetected in two patients. Thus, event recording is useful to distinguish recurrence of AVNT, sinus tachycardia, other types of supraventricular tachycardia, and atrial or ventricular premature beats, which all may be a reason of complaints during the first weeks after ablation. It provided a feeling of safety for symptomatic patients who often suffered from anxiety before the ablation.

Treatment of ventricular arrhythmias after recovery from myocardial infarction.

Demonstrated associations between postmyocardial infarction ventricular arrhythmias and a higher subsequent risk of both sudden and all-cause mortality have prompted a search for effective and safe treatment modalities. Recently completed clinical trials have provided a rationale for treatment recommendations in some specific settings. Beta-blocking therapy is recommended for postinfarction patients with frequent or complex ventricular premature beats. In contrast, calcium antagonist therapy is not helpful in these cases, and Class I antiarrhythmic therapy is actually harmful. Early indications of benefit from Class III antiarrhythmic therapies, particularly amiodarone, are under evaluation in large trials. Patients with sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) occurring late after myocardial infarction require therapy. Viable therapeutic methods include individualized antiarrhythmic therapy selected by the noninvasive approach, individualized antiarrhythmic therapy selected by the invasive approach, empiric amiodarone therapy, transcatheter or surgical ablative therapy (for VT), and use of an implantable cardioverter defibrillator. Clinical trial data have yet to determine which of these approaches is most effective under which circumstances. Postinfarction patients with nonsustained VT are the focus of several ongoing treatment trials. Early data suggest that risks requiring specific therapy are reached only by those patients who also have significant left ventricular dysfunction. The presence of inducible sustained ventricular tachycardia at an electrophysiologic study may further risk stratify such patients. High-risk patients with nonsustained ventricular tachycardia, left ventricular dysfunction, and inducible sustained ventricular tachycardia should participate in ongoing clinical trials. In the absence of this opportunity, intensive treatment should be considered.

Clinical and prognostic significance of serum magnesium concentration in patients with severe chronic congestive heart failure: The Promise Study

Objectives. The aim of this study was to determine the prognostic significance of alterations in serum magnesium in patients with moderate to severe congestive heart failure.Background. Reductions in serum magnesium have been postulated to play a role in promoting arrhythmias and to have an adverse impact on survival in congestive heart failure, although support for this postulate is lacking.Methods. Serum magnesium levels were measured in 1,068 patients enrolled in a survival study of class III or IV heart failure at the time of double-blind randomization to milrinone, a phosphodiesterase inhibitor, or placebo. All patients received conventional therapy with digoxin, diuretic drugs and a converting enzyme inhibitor throughout the trial. The median follow-up period was 6.1 months (range 1 day to 20 months).Results. Patients with high serum magnesium (defined as ≥1.9 mEq/liter, n = 242) were less likely to survive than were patients with a normal magnesium level (n = 627) (p < 0.05, risk ratio = 1.41). Patients with a low magnesium level (defined as ≤1.5 mEq/liter, n = 199) had no difference in survival compared with the group with a normal magnesium level (p = NS, risk ratio = 0.89). At baseline, the patients in the high magnesium group were older and had more severe functional and renal impairment. An analysis after adjustment for these variables demonstrated no difference in survival comparing the low, normal and high magnesium groups. Although the three groups had no difference in frequency of ventricular tachycardia, length of longest run or frequency of ventricular premature beats on baseline Holler monitoring, the group with hypomagnesemia had more frequent ventricular couplets.Conclusions. Serum magnesium does not appear to be an independent risk factor for either sudden death or death due to all causes in patients with moderate to severe heart failure. Hypomagnesemia is associated with an increase in the frequency of certain forms of ventricular ectopic activity, but this is not associated with an increase in clinical events. The higher mortality rate among the patients with hypermagnesemia is attributable to older age, more advanced heart failure and renal insufficiency.

Prognostic implications of asymptomatic ventricular arrhythmias: the Framingham Heart Study.

To evaluate the prevalence and prognostic significance of asymptomatic complex or frequent ventricular premature beats detected during ambulatory electrocardiographic (ECG) monitoring. Cohort study with a follow-up period of 4 to 6 years. Population-based. Surviving patients of the original Framingham Heart Study cohort and offspring of original cohort members (2727 men and 3306 women). One-hour ambulatory electrocardiography. The age-adjusted prevalence of complex or frequent arrhythmia (more than 30 ventricular premature complexes per hour or multiform premature complexes, ventricular couplets, ventricular tachycardia, or R-on-T ventricular premature complexes) was 12% (95% Cl, 11% to 13%) in the 2425 men without clinically evident coronary heart disease and 33% (Cl, 24% to 42%) in the 302 men with coronary heart disease. The corresponding values in women (3064 without disease and 242 with disease) were 12% (Cl, 11% to 13%) and 26% (Cl, 9% to 43%). After adjusting for age and traditional risk factors for coronary heart disease in a Cox proportional hazards model, men without coronary heart disease who had complex or frequent ventricular arrhythmias were at increased risk for both all-cause mortality (relative risk, 2.30; Cl, 1.65 to 3.20) and the occurrence of myocardial infarction or death from coronary heart disease (relative risk, 2.12; Cl, 1.33 to 3.38). In men with coronary heart disease and in women with and without coronary heart disease, complex or frequent arrhythmias were not associated with an increased risk for either outcome. In men who do not have clinically apparent coronary heart disease, the incidental detection of ventricular arrhythmias is associated with a twofold increase in the risk for all-cause mortality and myocardial infarction or death due to coronary heart disease. The preventive and therapeutic implications of these findings await further investigation.

Management of ventricular arrhythmias: then and now

To review the changing environment of antiarrhythmic therapy. The majority of articles chosen were written by experts in the field of arrhythmia management. The references include a pilot study, abstracts, original articles and results of study groups. An equal number of sources used in this article were obtained from fellow healthcare professionals and MEDLINE searches. Large, controlled clinical trials in which patient populations had structural heart disease, prior myocardial infarction and/or frequent ventricular premature beats. All were treated with either antiarrhythmic therapy or devices. Past research in the field of arrhythmia management has indicated that ventricular premature beat suppression is the key to increasing patient survival. After reviewing the results of such pivotal trials as the Cardiac Arrhythmia Suppression Trial, however, the question of whether to initiate therapy remains. Several trials investigating the efficacy of antiarrhythmic drugs in decreasing sudden death have yielded disappointing results. These trials have been beneficial, however, in classifying arrhythmias and assessing patient risk. The outcomes of these trials, combined with advances in the treatment of heart disease, provide us with a framework for antiarrhythmic therapy. Additional controlled clinical trials are necessary if we are to learn the best means of increasing survival in ventricular arrhythmia patients.

Ventricular premature beats in young subjects without evidence of cardiac disease: histological findings.

This report describes the results of right ventricle endomyocardial biopsies from 26 subjects (mean age 27 +/- 10 years) with premature ventricular beats and normal cardiac anatomy and mechanical function. Light microscopy examination revealed normal myocardium in 10 subjects (38%), acute myocarditis in two (7%), borderline myocarditis in one (3.5%), non-specific histological abnormalities including cellular hypertrophy, fibrosis and degenerative changes in 11 (42%), vasculitis in one (3.5%) and findings compatible with right ventricular dysplasia in the final subject (3.5%). The frequency of ventricular premature beats, as assessed by Holter monitoring, and the results of electrophysiological testing did not correlate with histopathological findings and their severity. These data indicate that some young subjects with premature ventricular beats of unknown origin have abnormal right ventricular biopsy findings. Adequate follow-up will probably demonstrate the clinical utility of these observations.

Ventricular arrhythmia in congestive heart failure

The importance of ventricular arrhythmia is based on its association with sudden death. In certain groups of patients, ventricular arrhythmia—primarily runs of nonsustained ventricular tachycardia (NSVT)—is associated with an increased risk for sudden death. Although this relationship has been most often reported in patients with recent myocardial infarction, it has also been recognized in patients with dilated cardiomyopathy, regardless of etiology. Therefore, ventricular arrhythmia is common in patients with CHF due to cardiomyopathy. A number of studies have reported that 70–95% of patients with cardiomyopathy and congestive heart failure (CHF) have frequent ventricular premature beats, and 40–80% will manifest runs of NSVT. Many factors are responsible for ventricular arrhythmia in such patients, including structural abnormalities, electrolyte imbalance, hemodynamic impairment, activation of neurohormonal mechanisms, and pharmacologic therapy. Many studies have reported a high yearly mortality in patients with cardiomyopathy and CHF; > 40% of deaths are sudden, most often the result of sustained ventricular tachyarrhythmia. Most studies have noted an association between presence (and frequency) of NSVT and risk of sudden cardiac death in these patients. Unfortunately, other techniques—such as the signal-averaged electrocardiogram and etectrophysiologic testing—are not helpful in identifying the individual at risk. Although several drug interventions will reduce mortality from progressive CHF, these drugs have not been shown to reduce sudden death and, indeed, have a variable effect on ventricular arrhythmia. Although NSVT is a marker for increased risk for sudden death, it is uncertain if antiarrhythmic drugs will prevent this outcome. Antiarrhythmic drugs have not been shown to be effective for preventing sudden death, although there are as yet no well-controlled randomized trials. Several studies suggest that amiodarone and β blockers are beneficial, but this requires confirmation. For patients who have been resuscitated following an episode of sudden death due to a sustained ventricular tachyarrhythmia, antiarrhythmic therapy guided by invasive and noninvasive techniques appears to reduce risk of recurrent arrhythmia. However, the response rate to antiarrhythmic agents is low and side effects are common in patients with CHF. Especially important is the increased risk of precipitating CHF and aggravating the arrhythmia being treated. For many such patients who have had serious ventricular tachyarrhythmia, the automatic implantable cardioverter defibrillator may prove a better option. Other drugs used for management of CHF reduce overall mortality, but not risk of sudden death.

Uses of statistical editing of real-time ambulatory electrocardiographic recordings for quantitative ventricular ectopic beat counts

Real-time ambulatory monitoring analyzes each heart beat, counts events, and stores ECG samples for later visual verification. Typically, a physician examines these to determine whether the computer algorithm accurately identified arrhythmias. Physician editing is performed using best clinical judgement. We developed a simple statistical editing procedure for adjusting false positive and false negative computer detections. In 20 subjects having 24-hr monitoring we compared statistically edited ventricular premature beat (VPB) counts and pair/run counts with the unedited monitor counts and with physician assessment using a visual counted gold standard. The agreement of the statistically edited count with the visual standard was 65% for total VPB, 85% for VPB pair/runs, and 90% for a risk score based on ventricular ectopy. Corresponding agreements for unedited monitor count were 15, 25, and 30%, respectively. Physician assessment was not sufficiently precise to allow quantitative count estimates. This study indicates a statistical editing procedure substantially increases the level of agreement between the visual standard and the monitor count of VPB frequency and complexity. Statistically edited data are suitable for quantitative counts of VPB and other arrhythmic events in research and in medical diagnosis and treatment. This editing procedure can be a useful adjunct to any ambulatory monitoring system.

Ventricular tachycardia in plasma cell dyscrasia syndrome

The syndrome of plasma cell dyscrasia with associated polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes is known as POEMS syndrome. Myocarditis is the only reported cardiac abnormality.’ We report a patient with POEMS syndrome who had highgrade ventricular tachyarrhythmias and underwent extensive electrophysiologic testing. A 35-year-old white man had a history of several months of weakness, numbness, and a burning sensation in the lower extremities. The patient had had a weight loss of 55 pounds and experienced impotency over the previous 6 months. Physical examination findings included wasting of the temporal muscle, hyperpigmentation, mild axillary lymphadenopathy, and frequent extrasystoles. Results of cardiovascular examination were otherwise normal. Neurologically the patient was unable to stand and had preserved strength in the upper extremities and bulbar muscles, areflexia, negative Babinskit signs, and loss of vibratory sensation in a stocking distribution over the lower extremities and to a lesser degree in the upper extremities. Laboratory values were creatine phosphokinase, 45 IU/L; thyroid-stimulating hormone, 7.5 mIU/ml (normal 0.15 to 3.2 mIU/ml); free thyroxine by dialysis, 1.3 ng/dl (normal 0.8 to 1.9 ng/dl); serum free testosterone, 2.8 pg/ml (normal >16 pg/ml); and serum immunoglobulin G, 2000 (normal <1650) with a monoclonal lambda band. A similar band was seen on protein electrophoresis of cerebrospinal fluid. Results of electromyography of muscles in the right leg were consistent with asymmetric demyelinating polyneuropathy. Results of biopsy of the left sural nerve revealed predominant axonal changes and biopsy of the gastrocnemius muscle revealed neurogenic atrophy. Computed tomography and a plain film of the pelvis demonstrated a lytic lesion in the left pubic ramus. Results of subsequent needle aspiration disclosed sheets of atypical plasmacytoid cells consistent with plasmacytoma. As seen on bone marrow study, plasma cells were moderately increased. ECG showed normal sinus rhythm, frequent ventricular premature beats (VPBs), PR interval 168 msec, QRS interval 104 msec, and QT interval 316 msec. During hospitalization the patient had frequent episodes of asymptomatic nonsustained ventricular tachycardia up to 40 beats at a rate of 160 beats/min (Fig. 1). During 24-hour Holter monitoring the patient had an average of 636 VPBs/hr with 268

Slow-Release Gallopamil Evaluated by Exercise Test and Long-Term Electrocardiography

The effects of slow-release gallopamil (100 mg b.i.d.) were studied on exercise-induced ST-segment depression as well as on spontaneous myocardial ischemia detected by long-term electrocardiography (ECG) monitoring for 48 h in 26 patients with coronary artery disease and angina pectoris. Eight patients had to be excluded (because of paroxysmal atrial fibrillation in four patients, development of unstable angina pectoris in three patients, and frequent ventricular premature beats in one patient). In the remaining 18 patients, gallopamil led to an increase of work load (W x min) evaluated by bicycle ergometry, paralleled by an increase of exercise duration until the occurrence of ST-segment depression of > or = 0.1 mV in the nonblinded part of the trial. The number of spontaneous episodes of myocardial ischemia during long-term ECG recording, ranging from 0 to 14 during control, decreased in patients with two or more episodes during control, paralleled by a decrease in the total duration of ischemic episodes and a decrease in the ischemic score (duration of episodes x maximal ST-segment depression). During long-term ECG monitoring, we observed asymptomatic episodes of spontaneous second degree atrioventricular block of the Wenckebach type in three patients. No other adverse effects of slow-release gallopamil were observed. Therefore, these preliminary results of the non-blinded protocol confirm the anti-ischemic effects of slow-release gallopamil given 100 mg b.i.d.; however, these promising results will have to be confirmed in the consecutive double-blind, placebo-controlled part of the trial.

Slow-Release Gallopamil Evaluated by Exercise Test and Long-Term Electrocardiography

The effects of slow-release gallopamil (100 mg b.i.d.) were studied on exercise-induced ST-segment depression as well as on spontaneous myocardial ischemia detected by long-term electrocardiography (ECG) monitoring for 48 h in 26 patients with coronary artery disease and angina pectoris. Eight patients had to be excluded (because of paroxysmal atrial fibrillation in four patients, development of unstable angina pectoris in three patients, and frequent ventricular premature beats in one patient). In the remaining 18 patients, gallopamil led to an increase of work load (W ± min) evaluated by bicycle ergometry, paralleled by an increase of exercise duration until the occurrence of ST-segment depression of ±0.1 mV in the nonblinded part of the trial. The number of spontaneous episodes of myocardial ischemia during long-term ECG recording, ranging from 0 to 14 during control, decreased in patients with two or more episodes during control, paralleled by a decrease in the total duration of ischemic episodes and a decrease in the ischemic score (duration of episodes ± maximal ST-segment depression). During long-term ECG monitoring, we observed asymptomatic episodes of spontaneous second degree atrioventricular block of the Wenckebach type in three patients. No other adverse effects of slow-release gallopamil were observed. Therefore, these preliminary results of the non-blinded protocol confirm the anti-ischemic effects of slow-release gallopamil given 100 mg b.i.d.; however, these promising results will have to be confirmed in the consecutive double-blind, placebo-controlled part of the trial.

Cardiac Disturbances in Patients with Obstructive Sleep Apnea

We studied the effect of nasal continuous positive airway pressure (nCPAP) on the occurrences of cardiac disturbances in 24 subjects with severe obstructive sleep apnea (OSA). Fifty percent of subjects were hypertensive, but none had symptoms or physical signs suggestive of cardiac disease. Subjects underwent overnight polysomnography with Holter monitoring on 2 consecutive nights (control and nCPAP). nCPAP significantly reduced the apnea/hypopnea index from 66 ± 5 events/h (mean ± SEM) on control nights to 6 ± 1 (p < 0.001 ). With nCPAP, only 7 ± 2 % of the night was spent with an arterial oxyhemoglobin saturation <90% as compared with 50 ± 5% on control nights (p < 0.001). No silent myocardial ischemia, severe bradycardia (HR < 30/min for > 1 min) or second degree A-V block were seen during either night. Prolonged sinus pauses (>2 s) were present in 2 subjects on control nights only, and were completely alleviated by nCPAP. Fifteen subjects (63 %) had ventricular premature beats (VPB) on control nights and in 5, these were complex (multiform or repetitive). With nCPAP, 13 subjects had VPB which were complex in 5. The group mean for VPB frequency was not significantly different between study nights. In conclusion, ventricular arrhythmias were common, whereas silent myocardial ischemia was not seen in patients with severe OSA with no evident heart disease. nCPAP relieved all sinus pauses, but had no significant effect on ventricular arrhythmias in this patient population. nCPAP may have a more important effect on cardiac disturbances in patients with OSA and coexistent significant cardiac disease.

Efficacy of disopyramide and mexiletine used alone or in combination in the treatment of ventricular premature beats

The efficacy of oral disopyramide and mexiletine used alone or in combination was studied in 75 patients with frequent ventricular premature beats (VPBs). The efficacy was evaluated with 24-hour ambulatory ECG and greater than or equal to 75% reduction in the number of VPBs was defined as effective. When disopyramide or mexiletine were ineffective or not tolerated, the alternative drug was administered and the efficacy was again evaluated. If the single administration of neither drug was effective, the combination of disopyramide and mexiletine was then given. Either disopyramide or mexiletine was effective in 48 patients, and neither drug was effective in 19 patients. In 19 patients unresponsive to both drugs, combination therapy was effective in six patients (32%). Both drugs caused side effects or one drug caused side effects and another drug was ineffective in eight patients. In five out of those patients, we attempted combined therapy with a reduced dosage of those drugs that caused side effects. This therapy was effective in two patients without intolerable side effects. Thus, when the single use of neither disopyramide nor mexiletine single-drug therapy is effective, it is worthwhile to try combination therapy. Also, combination therapy with a reduced dosage of the drugs that caused side effects might be the therapy of choice in patients who have developed dose-dependent side effects.

Evaluation of pentisomide on stable ventricular premature beats. Comparison with placebo

Pentisomide, a new class I anti-arrhythmic drug, was compared to placebo in 50 hospitalized patients with frequent (greater than 30 h-1) and stable ventricular premature beats (VPB) (variation less than 50% between two preliminary and one placebo 24-h Holter recordings). All patients underwent a single-dose acute oral testing followed by a short-term testing with 300 mg t.i.d. for 4 days and then by a 4-day placebo period. For the studied population, a 56.4% reduction of simple VPB and a 98.8% decrease of couplets and runs were the minimum required to define the drug efficacy and to exclude spontaneous variability, using the linear regression analysis. Pentisomide was found effective in 27 (54%) of the 50 patients after the acute test and in 23 (46%) after the short-term test. The drug induced a mild increase of PR and QRS intervals, while QTc, heart rate, blood pressure and ejection fraction showed no significant variations. Subjective tolerability was excellent.

Cardiac conduction defects associated with hyponatremia

Cardiac conduction defects have not been previously described in association with hyponatremia, although in patients with congestive heart failure the frequency of ventricular premature beats was found to correlate to the severity of hyponatremia. We describe three patients with second-degree or complete atrioventricular (AV) block which occurred during or shortly after an episode of severe hyponatremia. The first had thiazide-induced hyponatremia while on amiodarone. In the second, definite etiology for hyponatremia which was associated with longstanding polydipsia could not be established. The third had ischemic heart disease and intermittent conversion of his first-degree to second-degree AV block while hyponatremic after diuretics use. Although it is usually difficult to single out hyponatremia as the cause of conduction defects which usually occur in the presence of cardiac disease, potent medications or other electrolyte abnormalities, we suggest that hyponatremia may play a role in the pathogenesis of conduction defects in the diseased heart.

Cardiac Arrhythmias during Theophylline Toxicity: A Prospective Continuous Electrocardiographic Study

To examine the effects of theophylline toxicity on cardiac rhythm, patients underwent continuous ambulatory ECG recording during acute theophylline toxicity and recovery. The patients, who were recruited form inpatient wards, intensive care units, and emergency departments of a University Medical Center and a Veterans Administration Medical Center, had serum theophylline concentrations (STC) greater than 30 mg/L. There were 14 men and two women with a mean age of 66 years. Fourteen patients had COPD and developed toxicity following long-term theophylline overmedication. Two patients had asthma and ingested an intentional overdose. The STC at the onset of ECG recording ranged from 23 to 67 mg/L. The principal rhythm was sinus in 15 patients; one patient had atrial fibrillation. Sinus tachycardia (heart rate greater than 100/min) was common, and heart rate fell in proportion to STC as toxicity resolved. Supraventricular ectopic beats (SVEs) were noted in seven patients with multiple runs of SVE being present in four. One patient developed multifocal atrial tachycardia (MAT) during toxicity that resolved spontaneously. During the 11 +/- 8 hours of recording during toxicity (STC greater than 20 mg/L), 80 percent of patients had ventricular premature beats (VPBs), 44 percent had paired VPBs, and 25 percent had ventricular runs. One elderly patient with heart disease developed sustained ventricular tachycardia (VT) when STC = 66 mg/L. No other patient had ventricular ectopy that required intervention. During the 10 +/- 6 hours of recording during the "recovery phase" (STC less than 20 mg/L), all patients with VPBs continued to have ectopy; however, the number of VPBs declined significantly. A follow-up 24-hour ECG recording obtained one week after recovery from toxicity in the patient with sustained VT demonstrated marked reduction in the frequency and complexity of VPBs. Patients with frequent (greater than 10/h) or repetitive VPBs were older (p less than 0.05) than those without complex ectopy. There was a trend (p = 0.07) suggesting patients with underlying heart disease were at risk for having complex ventricular ectopy. We conclude that sinus tachycardia, SVE, and VPBs are common among patients with theophylline toxicity; however, sustained ventricular or supraventricular tachyarrhythmias that require antiarrhythmic therapy are uncommon.