Sharon A. Magro

Amiodarone pulmonary toxicity: prospective evaluation of serial pulmonary function tests

Pulmonary toxicity developed in 15 (17%) of 89 patients treated with amiodarone during a follow-up period of 2 weeks to 54 (mean 20 +/- 15) months. Prospective evaluation of serial pulmonary function tests in 67 patients demonstrated both a significant decrease from baseline in three of six variables in patients with toxicity at the time of diagnosis and a significant difference compared with the same variables in patients without toxicity. The most significant of these was the diffusing capacity for carbon monoxide (DLCO). An individual decrease in DLCO greater than or equal to 15% gave an optimal sensitivity of 100% and a specificity of 89% for the diagnosis of pulmonary toxicity. However, a decrease in DLCO greater than or equal to 15% did not alone warrant a change in therapy in asymptomatic patients. Although higher maintenance doses of amiodarone appeared to be related to the development of this complication, an abnormal baseline DLCO (less than 60% of predicted) with or without an initial abnormal chest roentgenogram did not predispose to pulmonary toxicity.

Importance of pacing site in entrainment of ventricular tachycardia

Transient entrainment by pacing has been demonstrated during various tachyarrhythmias, including ventricular tachycardia. A patient is described who had two morphologically distinct forms of sustained ventricular tachycardia induced by programmed stimulation. Entrainment of both configurations of ventricular tachycardia was demonstrated. Evidence for entrainment included the presence of different degrees of fusion between paced and ventricular tachycardia complexes at different pacing cycle lengths, and the observation that the last entrained beat was always unfused and identical in configuration to the ventricular tachycardia complexes. Termination of ventricular tachycardia only occurred at pacing cycle lengths at which there was loss of fusion. Catheter endocardial mapping suggested a septal origin of both configurations of ventricular tachycardia. Demonstration of entrainment was dependent on pacing site, being seen only during pacing in the ventricle opposite from that showing earliest activation during ventricular tachycardia. Thus, when attempting to entrain ventricular tachycardia, multiple pacing sites in both ventricles should be used.

Permanent triggered antitachycardia pacemakers in the management of recurrent sustained ventricular tachycardia

Permanent pacemakers capable of triggered ventricular stimulation were implanted in 28 patients with a history of sustained ventricular tachycardia or fibrillation. Noninvasive programmed ventricular stimulation was performed on 125 occasions during follow-up periods ranging from 1 to 25 months and was used to assess the efficacy of antiarrhythmic drug therapy, drug or dosage changes and left ventricular endocardial resection. Drug or dosage changes based on noninvasive programmed ventricular stimulation were made in 19 of the 28 patients. In addition, 126 episodes of spontaneous sustained ventricular tachycardia were terminated noninvasively in nine patients. It is concluded that a permanent pacemaker capable of triggered ventricular stimulation is useful in patients with ventricular tachycardia or fibrillation that is difficult to control.

Prospective comparison of right and left ventricular stimulation for induction of sustained ventricular tachycardia

Thirty-eight patients who had sustained monomorphic ventricular tachycardia (VT) or sudden cardiac death underwent programmed ventricular stimulation. To assess the relative efficacy of right and left ventricular (RV and LV) stimulation, a tandem protocol with 1 to 4 extrastimuli and burst pacing was used. Each step of the protocol was performed in a rotating sequence at the RV apex, basal RV septum and LV apex. Sustained VT was induced from the RV apex in 26 patients, right ventricle (either site) in 27, and LV apex in 24, and spontaneous VT was reproduced from those sites in 11, 14 and 12 patients, respectively. In the 23 patients who had sustained VT induced from both ventricles, RV stimulation always required fewer or the same number of extrastimuli for induction. At every stage of the protocol, the cumulative yield of sustained VT was consistently greater from the right ventricle than from the left ventricle. After delivering 4 extrastimuli and burst pacing, LV stimulation only increased the yield of sustained VT by 1 patient, and spontaneous VT by 3 patients. Inducibility or noninducibility in the right ventricle generally predicted the same outcome in the left ventricle. Previously undocumented VT or ventricular fibrillation was induced from the right ventricle in 19 patients and from the left ventricle in 13. Thus, LV stimulation was less efficacious than RV stimulation. LV stimulation increased the yield over RV stimulation only minimally and did not reduce the number of extrastimuli required to induce sustained VT.

Surgical treatment of right atrial focal tachycardia in adults

Although successful operative treatment of atrial focal tachycardia has been reported in children, there are only isolated reports of surgical treatment of this arrhythmia in adults. In this case series of eight patients (aged 10 to 53 years) with drug-resistant right atrial focal tachycardia, results of electrophysiologic studies, surgical techniques and long-term follow-up are described. Atrial focal tachycardia was reproduced during electrophysiologic study, and endocardial mapping localized the earliest onset of atrial activation in the right atrium in all patients. Epicardial mapping confirmed the location of atrial tachycardia foci in seven of eight patients whose tachycardia was inducible intraoperatively. Of four patients treated with epicardial cryoablation alone, two had recurrent tachycardia and required a second procedure. None have had arrhythmia recurrence. In all four patients after right atrial excision (two of whom had intraoperative recurrence of atrial focal tachycardia after epicardial cryoablation alone), there has been no recurrence during a clinical follow-up period of 11 to 67 months (mean 30). It is concluded that in adult patients 1) electrophysiologic study with endocardial and epicardial mapping permits successful surgical treatment of atrial focal tachycardia; 2) epicardial cryoablation alone may be associated with recurrence of atrial focal tachycardia either intraoperatively or postoperatively; and 3) subtotal right atrial resection appears to be a well tolerated procedure with no long-term recurrence of atrial focal tachycardia.

Electrophysiologic effects of ethmozin in patients with ventricular tachycardia

Ten patients with recurrent episodes of ventricular tachycardia (VT) had electrophysiologic studies in the basal state and on chronic oral ethmozin (12.1 +/- 0.6 SE mg/kg/day). Ethmozin significantly prolonged the AH interval (basal: 75 +/- 8 SE msec; ethmozin: 91 +/- 10 msec, p less than 0.05), the HV interval (51 +/- 3; 66 +/- 5 msec, p less than 0.01), and the QRS duration (101 +/- 4; 118 +/- 4 msec, p less than 0.001). Atrial and ventricular refractory periods and the corrected QT interval were not significantly affected by ethmozin. VT was induced in 7 of 10 patients in the basal state by means of programmed right ventricular extrastimulation or rapid burst ventricular pacing. On oral ethmozin nine patients had inducible VT. VT cycle length was consistently prolonged on ethmozin (250 +/- 13; 326 +/- 14 msec, p less than 0.001). Four of the seven patients with VT on basal ambulatory monitoring had total abolition of spontaneous VT on ethmozin. Ethmozin failed to prevent induction of VT in most patients despite significant reductions in ventricular arrhythmia on ambulatory monitoring. Further studies comparing VT induction with ambulatory monitoring in patients on ethmozin are needed to confirm these findings and to define the clinical significance of this dissociation.

Significant variability in the mode of ventricular tachycardia induction and its implications for interpretation of acute drug testing

Fifty-four patients with previous myocardial infarction and sustained ventricular tachycardia on fibrillation underwent two electrophysiologic studies in the drug-free state within 72 hours. Although the concordance of overall ventricular tachycardia induction over the 2 days was good (87% of patients), there was variability in the number of extrastimuli needed to induce sustained ventricular tachycardia on each day in 60% of patients. Of those in whom ventricular tachycardia was inducible on both days, 40% required additional extrastimuli and 20% required fewer extrastimuli. A change by two or more extrastimuli was found in 12% of patients. There was no correlation between the variability observed and multiple clinical and laboratory parameters (including the aggressiveness of the stimulation protocol); however, the direction of the variability (easier or harder to induce) correlated with changes in ventricular refractoriness. Inherent day-to-day variability may affect the reproducibility of electrophysiologic studies and influence the results of serial drug testing.

Electrophysiologic evaluation of pirmenol for sustained ventricular tachycardia secondary to coronary artery disease

The efficacy and electrophysiologic effects of pirmenol were evaluated in 21 patients with a history of sustained ventricular tachycardia (VT) and coronary artery disease. Intravenous pirmenol (0.7- to 1.1-mg/kg bolus, followed by a 35- to 40-micrograms/kg/min infusion) significantly prolonged the PR, QRS, QT and corrected QT intervals, HV interval and right ventricular effective refractory period, and shortened the sinus cycle length and atrioventricular nodal block cycle length. All 21 patients had inducible VT (20 sustained, 1 nonsustained) during programmed stimulation in the control state. After intravenous pirmenol, 5 patients (24%) no longer had inducible VT. In those in whom VT was still inducible, the VT cycle length was prolonged significantly. The 5 patients who responded to intravenous pirmenol were given oral pirmenol (200 to 250 mg every 8 hours) for 1 to 3 days and retested with programmed stimulation. In 4 of these 5, VT could not be induced with oral pirmenol administration; in 1 patient sustained VT was induced and pirmenol therapy was discontinued. Oral pirmenol suppressed recurrent VT during a follow-up of 315 +/- 133 days in 4 patients. However, pirmenol therapy was discontinued in 2 patients because of possible deleterious effects (worsened heart failure in 1 patient and elevated liver function test results in 1). Thus, pirmenol, a type IA antiarrhythmic drug, had an overall efficacy of approximately 19% in patients with sustained VT secondary to coronary artery disease.

Cumulative Effects of Amiodarone on Inducibility of Ventricular Tachycardia: Implications for Electrophysiological Testing

To determine whether the slow onset of action of amiodarone might result in a delayed effect on the inducibility of sustained ventricular arrhythmias. 45 patients with ischemic heart disease and inducible sustained monomorphic ventricular tachycardia were prospectively studied. Each patient had at least one initial repeat study on amiodarone and those with persistently inducible arrhythmias were rescheduled for further studies over the following 24 weeks. After 2–3 weeks of amiodarone therapy, nine patients no longer had inducible tachycardias, and tachycardia in another eight patients (18%) later became noninducible. Using life‐table methods, analysis based on the results of the first re‐study showed 18‐month recurrence rates of 43% in the inducible vs 17% in the noninducible groups (p = 0.056). When the results of additional testing were then used to reclassify patients, the recurrence rates for these two groups were 50% and 17%, respectively (p = 0.004). Observation of blood pressure and level of consciousness during induced arrhythmias was also predictive of clinical tolerance in patients having recurrences; 16 of 19 patients experienced symptoms of similar severity to those produced during testing. We conclude; (1) early testing of amiodarone may result in misclassification of some patients as remaining inducible; (2) re‐testing at a later time more accurately predicts tachycardia recurrence; (3) observation of hemodynamic response also provides important prognostic information.

Spontaneous arrhythmia detected on ambulatory electrocardiographic recording lacks precision in predicting inducibility of ventricular tachycardia during electrophysiologic study

This study investigates the relation of spontaneous ventricular arrhythmia on ambulatory electrocardiographic (ECG) monitoring to the subsequent inducibility of ventricular tachycardia during programmed electrical stimulation. Eighty patients (65 men, 15 women), whose mean age was 58 years, presented with one of the following: sustained ventricular tachycardia (n = 54); sudden death requiring resuscitation (n = 4); ventricular fibrillation (n = 11); or syncope thought to be of cardiac origin (n = 11). All patients had 24 hour ambulatory electrocardiograms and programmed electrical stimulation while receiving no antiarrhythmic therapy. Programmed electrical stimulation resulted in inducible sustained ventricular tachycardia (defined as a rate of greater than or equal to 120 beats/min for greater than or equal to 1 minute or requiring intervention) in 53 of the 80 patients. There was no measure of frequency or complexity of spontaneous arrhythmia detected on ambulatory ECG that could identify the degree of subsequent ventricular tachycardia inducibility during programmed electrical stimulation. In fact, 25% of patients who had inducible sustained ventricular tachycardia had little or no spontaneous arrhythmia on ambulatory ECG. Furthermore, of the 53 patients with inducible sustained ventricular tachycardia, 28 and 55% had no couplets or nonsustained ventricular tachycardia, respectively, during ambulatory monitoring. The combination of a clinical presentation of sustained ventricular tachycardia, confirmed coronary artery disease and a left ventricular ejection fraction of less than 30% had a better positive predictive value than did any ambulatory ECG criterion in predicting the inducibility of sustained ventricular tachycardia.