Calcium channel antagonism reduces exercise-induced ventricular arrhythmias in catecholaminergic polymorphic ventricular tachycardia patients with RyR2 mutations

Calcium channel antagonism in RyR2 defects. INTRODUCTION: Recently, gain-of-function mutations of cardiac ryanodine receptor RyR2 gene have been identified as a cause of familial or catecholaminergic polymorphic ventricular tachycardia. We examined the influence of the calcium channel blockers, verapamil and magnesium, on exercise-induced ventricular arrhythmias in patients with RyR2 mutations. METHODS AND RESULTS: Six molecularly defined catecholaminergic polymorphic ventricular tachycardia patients, all carrying a RyR2 mutation and on beta-adrenergic blocker therapy, underwent exercise stress test four times: at baseline, after verapamil and magnesium sulphate infusions, and finally, without interventions. The number of isolated and successive premature ventricular complexes during exercise ranged from 40 to 374 beats (mean 165 beats) at baseline, and was reduced during verapamil by 76+/-17% (P<0.05). Premature ventricular complexes appeared later and at higher heart rate during verapamil than at baseline (119+/-21 vs. 127+/-27 min-1, P<0.05). Magnesium did not inhibit the arrhythmias. Results in the fourth exercise stress test without interventions were similar to those in the first baseline study. CONCLUSIONS: This study provides the first in vivo demonstration that a calcium channel antagonist, verapamil, can suppress premature ventricular complexes and nonsustained ventricular salvoes in catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations. Modifying the abnormal calcium handling by calcium antagonists might have therapeutic value.     

Screening for ryanodine receptor type 2 mutations in families with effort-induced polymorphic ventricular arrhythmias and sudden death: early diagnosis of asymptomatic carriers

OBJECTIVES: We sought to establish the role of genetic screening for ryanodine receptor type 2 (RyR2) gene mutations in families with effort-induced polymorphic ventricular arrhythmia (PVA), syncope and juvenile sudden death. BACKGROUND: The RyR2 mutations have been associated with PVA, syncope and sudden death in response to physical or emotional stress. METHODS: We studied 81 subjects (39 males and 42 females; mean age 31 +/- 20 years) belonging to eight families with pathogenic RyR2 mutations. All subjects underwent screening for RyR2 mutations, electrocardiography (ECG), 24-h Holter monitoring, signal-averaged electrocardiography (SAECG), two-dimensional echocardiography and exercise stress testing. Electrophysiologic (EP) study was performed in nine patients. RESULTS: Six different RyR2 mutations were found in eight families. Forty-three family members carried the gene mutation. Of these, 28 (65%) showed effort-induced arrhythmic symptoms or signs and one died suddenly during follow-up. Family history revealed 19 juvenile cases of sudden death during effort or emotion. In two families sharing the same mutation, no subject presented with PVA during the stress test; thus, sudden death and syncope were the only clinical manifestations. The 12-lead ECG was normal in all but two subjects, whereas five patients showed positive late potentials on the SAECG. In 17 (39.5%) of 43 subjects, the two-dimensional echocardiogram revealed localized kinetic abnormalities and mild structural alterations of the right ventricle. The EP study was not able to induce PVA. CONCLUSIONS: The absence of symptoms and PVA on the stress test in more than one-third of carriers of RyR2 mutations, as well as the lack of PVA inducibility by the EP study, underlies the importance of genetic screening for the early diagnosis of asymptomatic carriers and prevention of sudden death.     

Influence of exercise on arrhythmias induced by digitalis-diuretic therapy in patients with atrial fibrillation

Serial low-level treadmill exercise testing was performed by 20 ambulatory patients with atrial fibrillation to provoke and study drug-related arrhythmias. All 20 were receiving long-term digitalis therapy; 19 were also receiving potassium-losing diuretic agents, and 3 had hypokalemia. The subjects were selected on the basis of resting electrocardiograms compatible with strong digitalis effects: prominent ST-T-U changes, intermittently occurring junctional beats, controlled ventricular rates (range 40 to 70/min) or ventricular premature beats. Arrhythmias suggesting digitoxicity were induced by exercise in all 20 subjects. Those occurring most often were junctional tachycardia with or without Wenckebach exit block, frequent ventricular premature beats and bigeminy. Idioventricular rhythm was induced in two subjects and ventricular parasystole in one. After withdrawal of digitalis and diuretic agents, subsequent exercise tests demonstrated increased ventricular rates, a decrease in ST-T-U changes and in the occurrence of most arrhythmias. In 18 patients, brief runs of junctional tachycardia persisted but occurred less often. Low-level exercise testing provides a simple method for provoking latent cardiac irritability in patients with suspected digitalis and diuretic toxicity; serial exercise testing after withdrawal of the drugs can demonstrate the devolution of arrhythmias.     

Diuretic-induced ventricular ectopic activity

The need to avoid hypokalemia during diuretic therapy in nondigitalized patients has been questioned. Twenty-one patients with (1) mild essential hypertension, (2) plasma potassium of < 3.5 meq/liter during previous diuretic treatment, and (3) normal findings {< 6 unifocal ventricular premature beats/hour} on 24-hour ambulatory electrocardiographic monitoring and exercise testing were treated with hydrochlorothiazide (50 mg twice a day) for four weeks and then ambulatory electrocardiographic monitoring and exercise testing were repeated. Ambulatory electrocardiographic monitoring revealed that ventricular ectopic activity developed in seven patients and complex ventricular ectopic activity (multifocal ventricular premature beats, ventricular couplets and/or ventricular tachycardia) in four. Only two of these seven had ventricular ectopic activity during exercise testing while they were hypokalemic. Potassium repletion in these seven patients with spironolactone abolished complex ventricular ectopic activity and reduced unifocal ventricular premature beats significantly (p < 0.01) from an average of 71.2 ventricular premature beats/hour/patient during hydrochlorothiazide treatment to 5.4 ventricular premature beats/hour/patient after potassium repletion. Although complex ventricular ectopic activity was more likely to occur with plasma potassium < 3.0 meq/ liter, restoration of normokalemia was required in several patients to abolish residual ventricular ectopic activity. Persistent ventricular ectopic activity in one patient suggested that myocardial injury sustained during hypokalemia may initiate chronic ventricular ectopic activity. Even in nondigitalized patients, the hazard of diuretic-induced ventricular ectopic activity warrants correction of hypokalemia.     

Combination antiarrhythmic therapy for management of malignant ventricular arrhythmia

The efficacy of combination drug therapy in the suppression of ambient ventricular arrhythmia was retrospectively evaluated in a study of 49 patients discharged from the hospital taking 2 membrane-active antiarrhythmic agents. Thirty-one patients (63%) had ischemic heart disease, 15 had miscellaneous cardiac disorders and 3 were free of ostensible heart disease. Therapy in all patients had previously been unsuccessful with an average of 3.7 single membrane-active drugs. Antiarrhythmic agents were discontinued for at least 48 hours to determine baseline arrhythmia levels by Holter monitoring and maximal exercise treadmill testing. Ventricular premature beats were evaluated according to the grading system of Lown and Wolf. Data on ventricular ectopic activity were obtained during Holter monitoring and exercise testing for both a control ("drug-free") period and for a period of combination therapy. During the control period, ventricular tachycardia was recorded during 23% of monitored hours, and the level was nearly twofold greater during stress testing. After institution of combined therapy, the percent of monitored hours of arrhythmia were reduced during Holter monitoring, with a greater reduction in couplets and ventricular tachycardia than in single ventricular premature beats. Ventricular tachycardia was more difficult to provoke by exercise testing in patients taking combination therapy than in control subjects. These data indicate that combination therapy can significantly reduce the density of ventricular ectopic activity in patients refractory to monotherapy. During an average follow-up of 26 months, 23 patients (47%) were able to receive decreased drug dosages, affording diminished adverse effects and improved tolerance to long-term use.     

Mutant ryanodine receptors in catecholaminergic polymorphic ventricular tachycardia generate delayed afterdepolarizations due to increased propensity to Ca2+ waves.

AIMS: Mutations in cardiac ryanodine receptors (RyR2s) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), characterized by risk of polymorphic ventricular tachyarrhythmias and sudden death during exercise. Arrhythmias are caused by gain-of-function defects in RyR2, but cellular arrhythmogenesis remains elusive. METHODS AND RESULTS: We recorded endocardial monophasic action potentials (MAPs) at right ventricular septum in 15 CPVT patients with a RyR2 mutation (P2,328S, Q4,201R, and V4,653F) and in 12 control subjects both at baseline and during epinephrine infusion (0.05 microg/kg/min). At baseline 3 and during epinephrine infusion, four CPVT patients, but none of the control subjects, showed delayed afterdepolarizations (DADs) occasionally coinciding with ventricular premature complexes. In order to study the underlying mechanisms, we expressed two types of mutant RyR2 (P2,328S and V4,653F) causing CPVT as well as wild-type RyR2 in HEK 293 cells. Confocal microscopy of Fluo-3 loaded cells transfected with any of the three RyR2s showed no spontaneous subcellular Ca(2+) release events at baseline. Membrane permeable cAMP analogue (Dioctanoyl-cAMP) triggered subcellular Ca(2+) release events as Ca(2+) sparks and waves. Cells expressing mutant RyR2s showed spontaneous Ca(2+) release events at lower concentrations of cAMP than cells transfected with wild-type RyR2. CONCLUSION: CPVT patients show DADs coinciding with premature action potentials in MAP recordings. Expression studies suggest that DADs are caused by increased propensity of abnormal RyR2s to generate spontaneous Ca(2+) waves in response to cAMP stimulation. Increased sensitivity of mutant RyR2s to cAMP may explain the occurrence of arrhythmias during exercise or emotional stress in CPVT.     

Prevalence of ventricular premature beats during stress testing in patients with exercise hypertension and the association with a positive family history of established hypertension

The prevalence of multiple ventricular premature beats during exercise testing was examined in 50 untreated patients with exaggerated systolic blood pressure response to exercise and 54 control subjects. Statistical analysis of the results showed significantly more frequent episodes of repetitive ventricular premature beats in the exercise hypertension group (this was present both in normotensive and mildly hypertensive individuals at rest). We also demonstrated that among normotensives there was a higher prevalence of exercise hypertension in those with a family history of established hypertension.     

Malignant premature ventricular beats in ambulatory patients.

The characteristics of premature ventricular beats predisposing to ventricular tachycardia or fibrillation were assessed by 24-h ambulatory monitoring and maximal treadmill exercise testing in 339 cardiac patients with premature ventricular beats. Premature ventricular beats were divided into early (Q-premature ventricular beat less than QT), late (within the last 20% of the cardiac cycle), and midcycle. Ventricular tachycardia was recorded in 45 patients and ventricular fibrillation, in three. The frequency of ventricular tachycardia or fibrillation was 32% in patients with late, 16% in patients with early, and 7% in patients with midcycle premature ventricular beats (P less than 0.05). Patients with frequent (less than 10/min) multiformed premature ventricular beats had a frequency of ventricular tachycardia or fibrillation of 44%, while only 13% of patients with frequent uniformed premature ventricular beats had ventricular tachycardia (P less than 0.05). Ambulatory patients with ventricular tachycardia or fibrillation have frequent multiformed premature ventricular beats, and the ventricular tachycardia or fibrillation is usually triggered by late premature ventricular beats.     

Tocainide for refractory symptomatic ventricular arrhythmias

Tocainide, an oral form of lidocaine, was employed in 120 patients with recurrent malignant ventricular arrhythmia refractory to conventional antiarrhythmic drugs. After discontinuation of all antiarrhythmic agents, patients underwent control studies including 48 hours of ambulatory electrocardiographc monitoring and maximal symptom-limited exercise testing. One hundred patients had frequent as well as repetitive ventricular premature beats whereas in 20 patients, because of infrequency of ectopic activity, invasive electrophysiologic studies were carried out to provoke a repetitive ventricular response.Tocainide therapy was begun at 1,200 mg daily and increased to 2,400 mg daily guided by drug efficacy and the occurrence of adverse effects. After 48 hours of treatment with a fixed dose, drug action was evaluated by repeat monitoring and exercise stress testing or electrophysiologic testing. Fifty-five patients (46 percent) responded to tocainide. The average daily dose of drug and peak blood levels were equivalent in responders and nonresponders. Adverse effects occurred in 42 patients (35 percent) and were primarily related to the central nervous system. Lidocaine predicted the response to tocainide in 78 percent of patients. Thirty-four patients were continued on long-term maintenance therapy. After an average follow-up period of 16 months (range 2 to 39), treatment with the drug was discontinued in nine patients. The remaining 25 patients have had no adverse effects and no recurrence of ventricular arrhythmia.     

Frequency and significance of cardiac arrhythmias in chronic obstructive lung disease

Ambulatory electrocardiograms obtained in 69 patients enrolled in the nocturnal oxygen therapy trial group were examined for frequency and significance of arrhythmias in patients with stable chronic obstructive lung disease. Ventricular premature beats occurred in 83 percent, ventricular bigeminy in 68 percent, paired ventricular premature beats in 61 percent, and nonsustained ventricular tachycardia in 22 percent of the patients. Supraventricular tachycardia occurred in 69 percent. Repetitive ventricular arrhythmia occurred in 64 percent of the patients, and was significantly more frequent in men and in patients with edema or elevated PCO2. Ventricular premature beats greater or equal to 25 per hour occurred in 35 percent of the patients. Univariate and multivariate Cox proportional hazards analysis showed that a history of coronary heart disease, increased sinus heart rate and decreased maximum work load (measured by maximal treadmill exercise test)--but not arrhythmias--were predictors of death.     

Evaluation of cardiac arrhythmias by exercise testing.

Exercise testing is an important noninvasive method for the exposure of arrhythmias. It provides complementary information to that obtained from ambulatory monitoring or electrophysiologic testing. By producing a number of important physiologic changes, especially activation of the sympathetic nervous system and an increase in circulating catecholamines, exercise testing provides a more complete assessment. On continuous monitoring, exercise-induced ventricular premature beats may be found in up to 34% of healthy subjects, in 60 to 70% of those with heart disease and in all patients who have experienced sustained ventricular tachycardia. Couplets or nonsustained ventricular tachycardia can be found during exercise in 0 to 6% of healthy subjects, in 15 to 31% of patients with heart disease and in 75% of those with sustained ventricular tachycardia. Even in patients with heart disease, there is only a small risk of inducing sustained ventricular tachycardia or ventricular fibrillation during exercise. The prognostic relevance of exercise-induced ventricular arrhythmias in patients with coronary artery disease or cardiomyopathy has not been clearly established. There appears to be an increased risk, however, in patients with ventricular premature beats as well as ST-segment depression or in patients with repetitive forms of ventricular arrhythmias during exercise which cannot be medically controlled. In healthy subjects, exercise-induced ventricular premature beats are of no prognostic relevance. In particular, for patients in whom arrhythmias are induced by exercise, exercise testing should be used to assess the effectiveness of antiarrhythmic drug treatment. Importantly, serious cardiac toxicity, often not observed at rest or during routine activities, may become apparent during exercise testing. It should be a standard part of arrhythmia assessment and management.     

Effects of sympathetic activation on ventricular ectopic beats in subjects with and without evidence of organic heart disease

In a selected group of 10 apparently healthy subjects and 22 patients with organic heart disease, all with frequent ventricular ectopic beats on Holter monitoring, we assessed the influence of sympathetic activation by comparing the arrhythmogenic effects of a symptom-limited bicycle exercise stress test and 90 degree head up tilt. Tilting reduced ventricular arrhythmias in the normal subjects (-48 +/- 18% from 9 +/- 2 beats min-1, P less than 0.05). Exercise stress testing caused small and insignificant changes in arrhythmias during the early (50-75 W) phases and an almost complete suppression of ventricular ectopic beats in the final stages (-99 +/- 1%, P less than 0.01). In six of the 10 subjects, ventricular arrhythmias reappeared in the early recovery phase. In the 22 patients with organic heart disease, tilting increased ventricular ectopic beats (43 +/- 17% from 9 +/- 3 beats min-1, P less than 0.05); augmented repetitive forms in 12 patients (179 +/- 88% from 1.4 +/- 0.6 per 3 min) and produced repetitive forms in six of the 10 remaining patients who did not show repetitive forms during control conditions. Exercise stress testing caused a marked increase in ectopic activity in the early phase (84 +/- 35%) while the response during the maximal phase of exercise as well as during recovery was related to the effort capabilities. Arrhythmias were increased in 12 patients with limited exercise duration and were reduced in 10 patients with good exercise tolerance. These data indicate that sympathetic activation has different effects on ventricular arrhythmias depending on the clinical setting and that tilting is a useful maneuver to evaluate the arrhythmogenic effects of increased sympathetic activity.     

Prognostic significance of exercise induced arrhythmias and echocardiographic variables in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HC) often presents with exercise-induced symptoms, including arrhythmias and sudden death. The investigators prospectively studied whether exercise testing is associated with immediate complications and if stress-induced arrhythmias and echocardiographic variables are associated with long-term adverse outcomes. Exercise echocardiography with 6-channel continuous monitoring for arrhythmias was performed in consecutive patients with HC clinically referred for the test. End points included death, myocardial infarction, revascularization, stroke, atrial fibrillation, ventricular tachycardia, and myectomy. Of 86 patients with HC (mean age 56.6 +/- 16.1 years) who underwent exercise echocardiography, arrhythmias occurred in 39 (45%), including 23 (27%) with premature atrial contractions, 2 (2%) with atrial fibrillation, 28 (33%) with premature ventricular contractions (16 also had atrial arrhythmias), and 1 (1.2%) with nonsustained ventricular tachycardia (hemodynamically stable). During a follow-up of 2.6 +/- 2.8 years, major events occurred in 11 patients (3 deaths, 5 revascularizations, 3 strokes). In addition, 12 patients developed atrial fibrillation, 6 developed nonsustained ventricular tachycardia, and 13 underwent myectomies. Variables associated with major events included hypertension, male gender, and worsening wall motion score index with exercise; increased exercise duration was associated with fewer events. ST-T changes on baseline electrocardiography and premature ventricular contractions were associated with atrial fibrillation risk. In conclusion, in this cohort of patients with HC, exercise testing was safe. Test results were associated with risk for adverse events.     

Predictive value of ventricular premature beats for subsequent ischaemic heart disease in apparently healthy subjects.

From 1978 to 1980, 260 healthy subjects, 40-79 years of age, underwent 24 h ambulatory electrocardiography in order to determine the prevalence and complexity of ventricular premature beats (VPBs) in adults without apparent heart disease. The number of types of VPBs seem in 5% or less were considered 'abnormal' and the present follow-up study undertaken in order to assess the significance of such 'abnormal' VPBs as predictors of subsequent ischaemic heart disease (IHD). Information concerning cardiac events within the follow-up period was available in 237 subjects. Nine were lost to follow-up and 24 refused clinical examination. IHD was documented in 13 (eight myocardial infarction, five angina pectoris). 'Abnormal' VPBs occurred in six out of 13 (46%) who later developed IHD compared to only 24 out of 213 (11%) without IHD (P less than 0.001). The presence of either more than 900 VPBs 24 h-1 or ventricular tachycardia of more than three beats, identified five out of 13 patients with IHD (sensitivity 38%), whereas 210 out of 213 with no evidence of IHD at follow-up were identified (specificity 98%). Four out of seven who initially had more than 900 VPBs 24 h-1 had IHD on follow-up. Our results have demonstrated a strong positive association between 'abnormal' VPBs observed in a random 24-h electrocardiographic recording of apparently healthy subjects 40-79 years of age and subsequent IHD. They also suggest that a 24-h ECG may be useful for the assessment of coronary risk even in asymptomatic subjects.     

Exercise-induced polymorphic ventricular tachycardia in adults without structural heart disease

Patients with catecholaminergic polymorphic ventricular tachycardia present at a young age with exercise-induced ventricular arrhythmias (VAs) and may have a positive family history. We describe 8 patients who presented with exercise-induced symptoms as adults, have a negative family history, and responded to beta-blocker therapy. The study evaluated exercise treadmill electrocardiographic data from patients referred for exercise-induced VA. Inclusion criteria consisted of development of bidirectional, pleomorphic, or polymorphic ventricular tachycardia with exercise, adult age at first onset, negative family history, and no evidence of structural heart disease. We correlated VA configurations with respect to heart rate before and after beta-blocker therapy. Patients displayed a pattern of increasing ventricular complexity with increasing heart rate. The appropriate beta blocker (n = 7) or calcium channel blocker (n = 1) was defined as the dose that resulted in control of symptoms. Three patients showed suppression of VA with sinus tachycardia at peak heart rate. Six patients had decreased VA defined as absence of higher complexity arrhythmias. With drug therapy, average heart rate associated with premature ventricular complex couplets/triplets increased, whereas duration and complexity of premature ventricular complexes decreased. One patient had an automatic implantable cardiac defibrillator placed but has had no discharges from the device since starting the appropriate beta blocker. In conclusion, these patients appear to respond well to beta-blocker or calcium channel blocker therapy with decreased ectopic complexity and an increased heart rate threshold for inducing VA.     

Catecholinergic ventricular tachycardia in children

Catecholinergic ventricular tachycardia is an adrenergic induced polymorphic ventricular arrhythmia. It occurs in infancy and is responsible for syncope and sudden death in the absence of any morphological cardiac abnormality. Without treatment the mortality in catecholinergic ventricular tachycardia is very high. We report genetic and clinical data from 25 cases of catecholinergic ventricular tachycardia referred with syncope (n=19) or resuscitated sudden death during exercise (n=6). A family history from the 25 families identified 41 apparent subjects considered as being clinically affected, with an average age of 30 +/- 10 years (11 to 62 years). Analysis of the RyR2 gene showed mutations in 13 of the 25 cases and in 39 of apparent subjects. With betablocker treatment (nadolol: 1.6 +/- 0.15 mg/kg), 96% of patients remained asymptomatic over an average follow-up of between 7.5 +/- 1.5 years, although some of them continued to display polymorphic ventricular extrasystoles on exercise. Nevertheless, 12% of the cases suffered sudden death or further syncope during follow-up. An automatic defibrillator was implanted in 2 patients who had a RyR2 mutation. High dose betablockers are effective in preventing serious rhythm disturbance in children. In adolescence, implanting an automatic defibrillator should be discussed in cases with a history of syncope or resuscitated sudden death. We confirm the importance of genetic studies in these families at high risk of sudden death.     

Determinants of survival in patients with malignant ventricular arrhythmia associated with coronary artery disease

The long-term survival data in patients with coronary artery disease and a history of malignant ventricular arrhythmia, defined as noninfarction ventricular fibrillation (VF) or hemodynamically compromising ventricular tachycardia (VT) followed for up to 9 years, were analyzed. In this group of 161 patients there was a total of 57 deaths, of which 35 (63%) were sudden. Life-table analysis demonstrated a 10% sudden death rate for all patients in the first year and a 7% annual rate in the subsequent 4 years. In patients managed noninvasively, the overall mortality rate was 27% over 9 years, or 3% per year. Suppression of ventricular tachycardia on both ambulatory monitoring and exercise testing was associated with improved survival. In patients evaluated by electrophysiologic testing the sudden death rate was 1.4% per year over an average of 5 years. This survival rate was not different compared with the noninvasive group (p = 0.09). Measures of left ventricular dysfunction and the frequency of ventricular arrhythmia before and after drug therapy were associated with a risk of sudden cardiac death by univariate analysis. Multivariate regression analysis identified 4 variables as independent predictors of sudden cardiac death: rales (p = 0.009), the number of runs of VT during exercise testing while receiving antiarrhythmic drug therapy (p = 0.0003), a history of congestive heart failure (p = 0.0009) and the number of premature beats on Holter monitoring (p = 0.01). These findings support the concept that suppression of repetitive arrhythmia on Holter monitor and exercise testing is a marker for improved survival among patients with malignant ventricular arrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventricular tachycardia in children

Thirty-eight patients aged 1 to 20 years (mean 11.2) were evaluated because of recurrent ventricular tachycardia. The follow-up period ranged from 0.5 to 12 years (mean 6). The patients were separated into two groups according to the presence or absence of known structural heart disease. Seventeen of the 21 patients with known heart disease were symptomatic (cardiac arrest in 5, syncope in 5, dizziness in 7) compared with only 6 of the 17 patients without heart disease (syncope in 3 and dizziness in 3) (p <0.01). All symptomatic patients had ventricular tachycardia with rates of more than 150 beats/min, whereas all but one of the asymptomatic patients had rates of less than 150 beats/min (p <0.01). Graded treadmill exercise testing was performed in 21 of the 38 patients. Exercise increased the degree of ventricular arrhythmia in 8 of the 11 symptomatic patients but decreased or abolished the arrhythmia in 9 of the 10 asymptomatic patients (p <0.01).Antiarrhythmic therapy was used in 28 of the 38 patients. Effectiveness of therapy was assessed with both 24 hour Holter monitoring and graded treadmill exercise testing. Therapy effectively abolished ventricular tachycardia and greatly decreased the number of premature ventricular complexes in the symptomatic patients but was less effective in the asymptomatic patients. Thus, this study suggests that the presence of underlying heart disease, the rate of ventricular tachycardia and the results of graded treadmill exercise tests are important in predicting the prognosis of children with ventricular tachycardia.     

Cardiac arrhythmias during the combined use of beta-adrenergic agonist drugs and theophylline

We studied 15 nonsmoking, clinically stable asthmatic subjects aged 27 to 39 years to evaluate the potential cardiotoxic effects of combined use of a beta-adrenergic agonist drug and theophylline in the treatment of asthma. Subjects underwent a one-week washout period followed by two one-week periods of study receiving either oral terbutaline or sustained-release theophylline during week 1 and both drugs during week 2. Thirty-six-hour Holter monitoring was performed at the end of each period of study. No significant increase in the total number of ventricular premature beats was noted, although the average heart rate increased significantly between each period of study. Although not statistically significant, the number of individuals with multiform or complete and repetitive ventricular premature beats increased from one at baseline to three during each period of study, including one subject with ventricular tachycardia on combined therapy. These data suggest that combined therapy with theophylline and a beta-adrenergic agonist in young, otherwise healthy asthmatic subjects does not lead to an increase in the total number of ectopic beats but may increase the degree of complexity of ventricular premature beats.     

The natural history of cardiac involvement in myotonic dystrophy: an eight-year follow-up in 17 patients

We evaluated the progression of conduction system and myocardial disease in 17 asymptomatic myotonic dystrophy patients by clinical evaluation, electrocardiography, vector cardiography, and echocardiography. An exercise test was done in 10 patients. After 8 years, a follow-up study of 12 of the 17 original patients was done with a similar protocol. During this period, 2 patients died: one of sudden death while the other had acute left ventricular failure. In our first control study, we found EKG abnormalities in 15 of our patients, consisting mostly of conduction defects or pseudonecrotic patterns. In our second control, all patients had conduction system disease and, in addition, 3 of them had premature ventricular beats. One patient developed dilated cardiomyopathy. In 6 patients, structural involvement of the right ventricle was found. We conclude that even in asymptomatic myotonic dystrophy patients a conduction system deficit is present and progresses, and cardiac death may occur in about 12% of these patients.