Management of recurrent ventricular tachycardia: economic impact of therapeutic alternatives

The clinical and economic results of antiarrhythmic therapy selected on the basis of electrophysiologic (EP) studies in patients with recurrent ventricular tachycardia (VT) were examined and compared with previously administered empiric therapy. Twenty-nine patients with recurrent VT and organic heart disease, aged 39 to 78 years (mean 59 +/- 11) were evaluated. All patients had empiric therapy before EP studies and EP-based therapy after EP evaluation. Hospital records were analyzed from arrhythmia diagnosis 1 to 39 months (mean 7.5 +/- 10.4) before EP evaluation until completion of follow-up 1 to 20 months (mean 13.3 +/- 7.4) after EP studies. Clinical efficacy was assessed by comparing actual arrhythmic deaths or recurrences during EP-based therapy with predicted values on empiric therapy. Charges based on diagnosis-related groupings for empiric and EP-based therapy were compared. Charges for EP evaluation were included in the calculation for EP-based therapy. During empiric therapy, 1 to 7 unsuccessful drug trials (mean 3.7 +/- 1.6) were performed, with arrhythmia recurrences noted in all patients during a mean 7.5-month VT duration. Twenty-seven of 29 patients required 1 to 70 electrical terminations. There were 64 hospitalizations (mean 2.1 +/- 1.7) with a total length of hospital stay of 913 days (mean 31.0 +/- 19.9). EP evaluation required 90 EP procedures (mean 3.0 +/- 1.5) with a length of stay of 690 days (mean 23.8 +/- 12.0). During a follow-up period of 1 to 26.5 months (13.3 +/- 7.4) on EP-based therapy, 1 patient died suddenly.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic effects of amiodarone in patients with refractory ventricular tachycardia

We examined the chronic electrophysiologic, systemic, and pharmacologic effects of chronic oral amiodarone therapy in 24 patients with refractory ventricular tachycardia and organic heart disease. Chronic amiodarone therapy resulted in significant increases in R-R interval (from 798 +/- 182 msec to 912 +/- 100 msec; P less than 0.01), P-R interval (from 205 +/- 66 msec to 221 +/- 87 msec; P less than 0.02), QRS duration (from 103 +/- 24 msec to 115 +/- 28 msec; P less than 0.001), and Q-Tc interval (from 413 +/- 48 msec to 470 +/- 46 msec; P less than 0.001). Significant increases were also noted in P-A interval (from 36 +/- 14 msec to 45 +/- 13 msec; P less than 0.05), A-H interval (from 119 +/- 61 msec to 141 +/- 87 msec; P less than 0.02), and H-V interval (from 52 +/- 12 msec to 64 +/- 11 msec; P less than 0.001). Electrophysiologic parameters showing changes included corrected sinus node recovery time (from 271 +/- 140 msec to 425 +/- 122 msec; P less than 0.01), the effective refractory period of the atrium (from 263 +/- 32 msec to 321 +/- 47 msec; P less than 0.01), the effective refractory period of the atrioventricular node (from 348 +/- 109 msec to 478 +/- 157 msec; P less than 0.001), the effective refractory period of the ventricle (from 253 +/- 21 msec to 291 +/- 28 msec; P less than 0.001), the atrial pacing cycle length producing A-V nodal Wenckebach (from 436 +/- 109 msec to 531 +/- 95 msec; P less than 0.001), and the functional refractory period of the A-V node (from 422 +/- 68 msec to 499 +/- 95 msec; P less than 0.001). Programmed electrical stimulation performed after 21-88 (mean 31) days of treatment was highly predictive of long-term results if suppression of arrhythmia induction was demonstrated (12 patients) or if the spontaneous arrhythmia was reinduced (5 patients). Induction of morphologically new ventricular tachyarrhythmias was frequent (42%) but had a low spontaneous recurrence rate (10%) during follow-up. Systemic parameters on chronic amiodarone therapy showed significant increases in total T4 and reverse T3, with no change in pulmonary function tests or left ventricular ejection fraction. Serum amiodarone levels at chronic electrophysiologic study ranged from 0.44-4.10 (mean 1.3) micrograms/ml. Long-term follow-up (2.5 to 20 months) demonstrated a marked improvement in clinical symptoms and mortality, but a significant recurrence rate of a well-tolerated slower arrhythmia persisted. Adverse effects on chronic amiodarone therapy were frequent (10 patients) and often disabling but required drug discontinuation in only 1 patient.     

Method for the rapid and atraumatic insertion of permanent endocardial pacemaker electrodes through the subclavian vein.

One hundred sixty-four permanent pacemaker implantations through the subclavian vein were accomplished by 17 different physicians at four institutions utilizing a specially constructed peel-away introducer. Fourteen attempts (8.3 percent) to cannulate the subclavian vein were unsuccessful. There were four cases of pneumothorax (2.4 percent) and two cases of hematoma formation (1.2 percent). The procedure has the advantage of a rapid and atraumatic insertion of a variety of transvenous pacemaker electrodes, and the avoidance of surgical dissection for a venous entrance site.     

Cardiac pacing in the 1980s: Treatment and techniques in transition

The pacemaker of the 1980s is designed to maintain atrioventricular synchrony through dual-chamber pacing. This pacemaker is multiprogrammable and capable of telemetric transmission of biologic, electronic and electrophysiologic data. Several developments have made this therapeutic modality possible: 1) the cumulative survival rate of many lithium-battery pacemakers exceeds 95% at 5 years; 2) lead and connector problems are rare; 3) atrial and ventricular electrode malfunctions occur in less than 2% of implants; and 4) new introducer techniques have simplified implantation (mortality and major morbidity rates are 0.5 and 0.4%, respectively). With multiprogrammability, pacemaker function can be optimized for the patient's needs, and about 20% of reoperations can be avoided.Ninety-six dual-chamber (DDD) pacemakers, 55 of which have been followed up for more than 3 months, have provided trouble-free performance and have yielded salutary clinical results, particularly when implanted to replace previous ventricular inhibited units. Problems with these pacemakers have included unusual pacing electrocardiograms, pacemaker eccentricities, programmer maintenance, pacing and follow-up complexities and costs.In the 1980s, effort will be required to find a balance between rapidly evolving technology and the clinical need for complex pacing systems. From 1978 to 1981, the rate of pacemaker implantation grew from 309 to 513 implants per million population per year, and there are now approximately 500,000 patients with implanted pacemakers living in the United States. Indications for pacing are ill-defined, because in many cases the assessment of clinical response to pacing is largely subjective, lacking satisfactory quantitative indexes. This decade will be a time of reappraisal of the extent of clinical applicability of new techniques, particularly the multi-programmable dual-chamber system which, after 3 years of clinical trial, shows promise of being the predominant pacemaker of the immediate future.     

Permanent pacing of the heart: 1952 to 1976.

The theory and science of electrical pacing of the heart is scarcely 2 decades old, but developments in these areas have in a way revolutionized modern cardiology. This report, basically a review of the major developments during that time, describes the present state of the art, and calls attention to the many people who have brought us to this point. Results of a recent national survey reveal that about 156,000 patients in the United States are living with implanted pacemakers or about 1 in every 1,300 persons. The rate of new implants is 270/million each year, the highest in the world. The impact of such a volume is considerable, affecting industrial growth, federal legislation and control, insurance plans and a multitude of medical programs. New power sources, some touted to last a lifetime, will have a great impact but will not change the current state of the art materially because 30 percent or more of pacemaker operations are for problems other than routine battery exhaustion. The need for improvements in other pacemaker components is emphasized.     

Clinical efficacy and electrophysiology of oral propafenone for ventricular tachycardia

Sixteen patients with ventricular tachycardia (VT) or nonfatal cardiac arrest were treated with propafenone (P), 900 mg/day. Electrophysiologic studies were performed before and during therapy with P. All patients had inducible sustained VT at the baseline study. During P therapy, VT was not inducible in 1 patient, was unsustained in 1 and was harder to induce in 2 patients. P increased the cycle length of VT from 307 ± 67 to 382 ± 107 ms. Five patients began outpatient therapy with P, including 2 in whom VT was slowed to < 125 beats/min. Two are arrhythmia-free during follow-up of 2 and 8 P significantly increased intraatrial conauction time (from 44 ± 12 to 72 ± 22 ms), AH interval (from 115 ± 36 to 152 ± 45 ms), HV interval (from 55 ± 18 to 92 ± 42 ms), QRS duration (from 140 ± 36 to 180 ± 48 ms) and QT interval (from 402 ± 30 to 459 ± 60 ms). P increased atrial (from 247 ± 36 to 288 ± 38 ms) and ventricular (from 249 ± 20 to 277 ± 32 ms) effective refractory periods, Sinus cycle length did not change, but the corrected sinus node recovery time increased (from 162 ± 85 to 821 ± 1,607 ms). P aggravated arrhythmias in 4 patients. The plasma P concentration, measured either at the time of electrophysiologic studies or when therapy was discontinued, was 753 ± 428 ng/ml. P suppressed ventricular ectopic beats in 33 % and increased them in 1 patient. P has antimonths. arrhythmic activity against VT similar to that of other antiarrhythmic drugs and has potential for serious adverse effects in some patients.     

Clinical efficacy and electrophysiology of imipramine for ventricular tachycardia

Invasive electrophysiologic studies were performed before and during treatment with imipramine in 18 patients with inducible ventricular tachycardia (VT). All received imipramine, 50 mg twice daily for 3 days, and then 100 mg twice daily for 3 days. Imipramine increased the infranodal conduction times (HV) (from 58 +/- 7.8 to 65 +/- 10 ms) and QRS duration (from 133 +/- 21 to 153 +/- 39 ms) and significantly decreased sinus cycle length (from 875 +/- 145 to 711 +/- 116 ms) and maximal corrected sinus nodal recovery time (from 457 +/- 656 to 380 +/- 603 ms). The Wenckebach cycle length tended to decrease and the QT interval to increase, but these changes were not statistically significant. Atrial and ventricular refractory periods, atrioventricular nodal conduction times and induced VT cycle length did not change significantly. Imipramine prevented induction of VT in 2 patients, and VT was more difficult to induce in 1 patient. These 3 patients received chronic imipramine therapy. The 2 patients in whom no VT could be induced while taking imipramine have had no recurrence of arrhythmia at 6 and 12 months of follow-up. The third patient died suddenly 4 months after discharge from the hospital. One patient had worsening of arrhythmias while taking imipramine and 61% had minor adverse effects. The mean combined plasma imipramine and desmethylimipramine concentration at the time of the repeat electrophysiologic study was 227 +/- 114 ng/ml. Imipramine is effective against VT in some patients; however, like other type I antiarrhythmic drugs, the rate of efficacy is low.     

Polymorphous ventricular tachycardia: clinical features and treatment.

Thirty-four cases of ventricular tachyarrhythmia characterized by polymorphy of the QRS complexes with changing R-R intervals and a heart rate of 150 to 300 beats/min, termed polymorphous ventricular tachycardia, are described. The factors involved in the appearance of this arrhythmia were the administration of antiarrhythmic drugs (quinidine 22 patients, procainamide 5 patients, ajmaline 1 patient), antianginal drugs (prenylamine [Synadrin] 4 patients) and antidepressant drugs (thioridazine 1 patient). Twenty-one patients were treated for premature ventricular complexes, three for chronic recurrent ventricular tachycardia, six for atrial flutter and fibrillation, three for anginal pain and one patient for mental depression. All patients except one had a drug-induced prolonged corrected Q-T interval before the appearance of polymorphous ventricular tachycardia. Most of the patients with this arrhythmia were considered to have severe myocardial disease. Lidocaine and electric cardioversion were administered to all patients, but were effective only in seven patients whose tachycardia occurred in short, single episodes. The most effective treatment (17 patients) was temporary ventricular pacing at rates ranging from 100 to 140 beats/min. Intravenous isoproterenol proved to be successful in another 10 cases. It is concluded that patients with severe myocardial involvement receiving antiarrhythmic drugs for premature ventricular complexes, especially the multiform variety, are at high risk for the development of polymorphous ventricular tachycardia.     

Evaluation of aortic stenosis by continuous wave Doppler ultrasound

Twenty-four patients with suspected aortic stenosis (Group I) were evaluated noninvasively by continuous wave Doppler ultrasound before undergoing cardiac catheterization. Twenty normal subjects served as the control group (Group II). Maximal velocity measurements in the ascending aorta ranged from 3.0 to 5.8 m/s (mean 4.34 +/- 0.65) in Group I versus 1.0 to 1.6 m/s (mean 1.28 +/- 0.16) in Group II (p less than 0.001). Using the Bernoulli equation, the peak pressure gradient across the aortic valve was calculated from the maximal velocity in the Group I patients. The results correlated well with the peak aortic valve gradient obtained at cardiac catheterization (r = 0.79). In 20 of these 24 patients, the peak Doppler gradient was within 25% of the gradient found at cardiac catheterization. In three patients, the Doppler study under-estimated the gradient by slightly more than 25% but still detected the presence of significant aortic stenosis. The Doppler technique failed to detect critical aortic stenosis in only one patient. Significant overestimation of the gradient by Doppler measurement did not occur in any patient. The technique was particularly helpful in older patients in whom other noninvasive tests often yield inconclusive results. An important but infrequent limitation of the technique is underestimation of the gradient that occurs when the angle of incidence between the ultrasound beam and aortic blood flow is too large. The findings indicate that continuous wave Doppler ultrasound provides a reliable estimate of the valvular gradient in most patients with aortic stenosis.     

Relative efficacy of blind left ventricular aneurysm resection for the treatment of recurrent ventricular tachycardia

Coronary arterial bypass grafting and left ventricular aneurysm resection and the two combined have been reported effective in control of refractory ventricular tachyarrhythmias; 82 percent of a pool of 127 patients (from 22 reports) survived after surgery. However, the follow-up period in this group is short and the extent of medical therapy is not well defined. Actuarial analysis of results of conventional left ventricular aneurysm resection in 32 Stanford patients with well documented ventricular tachyarrhythmias shows an arrhythmia recurrence rate of 50 ± 9 percent (mean ± standard error of the mean) during the postoperative hospitalization. In contrast, after 10 months only 11 ± 9 percent of 18 patients who underwent myocardial resection guided by intraoperative electrical activation sequence mapping experienced arrhythmia recurrence.These data demonstrate that simple left ventricular aneurysm resection is less effective in preventing ventricular tachyarrhythmias than originally believed. Preliminary data suggest that surgery of the left ventricle guided by intraoperative mapping may provide more effective control of ventricular tachyarrhythmias. However, intraoperative mapping has many technical and interpretive problems. Investigations are needed to determine the roles of conventional and new operative approaches to treatment of medically refractory ventricular tachyarrhythmias.     

Quantitative assessment of pulmonary hypertension in patients with tricuspid regurgitation using continuous wave Doppler ultrasound

Doppler ultrasound examination was performed in 69 patients with a variety of cardiopulmonary disorders who were undergoing bedside right heart catheterization. Patients were classified into two groups on the basis of hemodynamic findings. Group I consisted of 20 patients whose pulmonary artery systolic pressure was less than 35 mm Hg and Group II consisted of 49 patients whose pulmonary artery systolic pressure was 35 mm Hg or greater. Tricuspid regurgitation was detected by Doppler ultrasound in 2 of 20 Group I patients and 39 of 49 Group II patients (p less than 0.001). Twenty-six of 27 patients with pulmonary artery systolic pressure greater than 50 mm Hg had Doppler evidence of tricuspid regurgitation. In patients with tricuspid regurgitation, continuous wave Doppler ultrasound was used to measure the velocity of the regurgitant jet, and by applying the Bernoulli equation, the peak pressure gradient between the right ventricle and right atrium was calculated. There was a close correlation between the Doppler gradient and the pulmonary artery systolic pressure measured by cardiac catheterization (r = 0.97, standard error of the estimate = 4.9 mm Hg). Estimating the right atrial pressure clinically and adding it to the Doppler-determined right ventricular to right atrial pressure gradient was not necessary to achieve accurate results. These findings indicate that tricuspid regurgitation can be identified by Doppler ultrasound in a large proportion of patients with pulmonary hypertension, especially when the pulmonary artery pressure exceeds 50 mm Hg. Calculation of the right ventricular to right atrial pressure gradient in these patients provides an accurate noninvasive estimate of pulmonary artery systolic pressure.     

Efficacy of verapamil in chronic, recurrent ventricular tachycardia

Verapamil, 0.25 mg/kg, was given to 24 patients with chronic, recurrent ventricular tachycardia (VT) whose clinical tachyarrhythmias were reproduced at electrophysiologic study. Seven patients (29%) responded acutely to verapamil: VT was not inducible in 5 and spontaneously terminated within 5 seconds of induction in 2 patients in whom it was previously sustained. Four of the 7 responders had no identifiable structural heart disease, and 3 had coronary artery disease. Responders were younger and had better left ventricular function than did nonresponders. Long-term therapy with verapamil, attempted in 5 of the 7 responders, was effective in 3, ineffective in 1, and of uncertain efficacy in 1. Verapamil therapy was discontinued because of worsened congestive heart failure in 2 patients.

The short-term efficacy of verapamil in these patients compares favorably with the efficacy of other antiarrhythmic agents against VT induction in patients with long-term, recurrent, drug-refractory VT. The short-term efficacy of verapamil correlated with its long-term efficacy. These observations provide preliminary evidence that verapamil may be useful in the treatment of some patients with recurrent VT. When standard drugs are not effective, verapamil should be given a trial, especially in young patients with good left ventricular function.     

Long-term efficacy and toxicity of high-dose amiodarone therapy for ventricular tachycardia or ventricular fibrillation

Amiodarone was administered to 154 patients who had sustained, symptomatic ventricular tachycardia (VT) (n = 118) or a cardiac arrest (n = 36) and who were refractory to conventional antiarrhythmic drugs. The loading dose was 800 mg/day for 6 weeks and the maintenance dose was 600 mg/day. Sixty-nine percent of patients continued treatment with amiodarone and had no recurrence of symptomatic VT or ventricular fibrillation (VF) over a follow-up of 6 to 52 months (mean ± standard deviation 14.2 ± 8.2). Six percent of the patients had a nonfatal recurrence of VT and were successfully managed by continuing amiodarone at a higher dose or by the addition of a conventional antiarrhythmic drug. One or more adverse drug reactions occurred in 51% of patients. Adverse effects forced a reduction in the dose of amiodarone in 41 % and discontinuation of amiodarone in 10% of patients. The most common symptomatic adverse reactions were tremor or ataxia (35 %), nausea and anorexia (8%), visual halos or blurring (6%), thyroid function abnormalities (6%) and pulmonary interstitial infiltrates (5%).Although large-dose amiodarone is highly effective in the long-term treatment of VT or VF refractory to conventional antiarrhythmic drugs, it causes significant toxicity in approximately 50% of patients. However, when the dose is adjusted based on clinical response or the development of adverse effects, 75 % of patients with VT or VF can be successfully managed with amiodarone.     

Clinical spectrum of ventricular tachycardia with left bundle branch morphology

Twenty-nine patients with apparent ventricular tachycardia (VT) of left bundle branch block (LBBB) morphology were evaluated. Tachycardia was associated with an organic basis in 24 of 29 patients: 7 had Mahaim fibers of the nodoventricular type, 7 had arrhythmogenic right ventricular dysplasia, 5 had coronary heart disease, 3 had biventricular cardiomyopathy, and 2 had associated congenital heart disease. In many patients the underlying cardiac disease was not readily apparent. In the patients with a Mahaim fiber, the electrocardiogram taken during sinus rhythm was frequently normal. A reentry tachycardia with anterograde conduction over the nodoventricular fiber could mimic VT as diagnosed by the usual criteria; nodoventricular fibers were, therefore, often unsuspected before electrophysiologic evaluation. In patients with arrhythmogenic right ventricular dysplasia, cineangiography demonstrated abnormalities of the right ventricle, but only minor or no abnormalities of the left ventricle. Clinical and electrocardiographic features were not distinctive. Of the 29 patients, 22 had serious symptoms accompanying the tachyarrhythmia or had required cardioversion. Patients were followed up for an average of 20 months: 4 patients died. Thus, VT exhibiting an LBBB morphology is not uncommon and is frequently associated with organic heart disease, serious symptoms, and significant mortality. Right ventricular angiography and electrophysiologic study may clarify the diagnosis in these patients.