William M. Miles

Regional cardiac sympathetic denervation in patients with ventricular tachycardia in the absence of coronary artery disease

OBJECTIVESnThe aim of this study was to determine whether patients with ventricular arrhythmias in the absence of coronary artery disease also have abnormalities in sympathetic innervation.nnnBACKGROUNDnWe have previously shown by cardiac sympathetic scintigraphy using iodine-123-metaiodobenzylguanidine (I-123-MIBG) that patients with ventricular tachycardia after myocardial infarction have regional cardiac sympathetic denervation. It is not known whether patients with ventricular tachycardia in the absence of coronary artery disease also have regional cardiac sympathetic denervation.nnnMETHODSnWe performed cardiac I-123-MIBG and thallium-201 single-photon emission computed tomographic (SPECT) scans at rest in 18 patients (mean age 47 +/- 18 years) with cardiomyopathy (n = 6), left ventricular hypertrophy (n = 1), valvular disease (n = 2) or a structurally normal heart (n = 9) who presented with monomorphic (n = 15) or polymorphic (n = 3) ventricular tachycardia. These scans were compared with scans in 12 control patients without ventricular tachycardia (mean age 30 +/- 17 years) who had cardiomyopathy (n = 3) or a structurally normal heart (n = 9). Cardiac sympathetic denervation was defined as myocardial areas having thallium uptake with reduced or absent I-123-MIBG uptake.nnnRESULTSnTwelve (67%) of 18 patients with ventricular tachycardia had regional cardiac sympathetic denervation compared with 1 (8%) of 12 patients who did not have ventricular tachycardia (p = 0.002). In the nine patients with a structurally normal heart and ventricular tachycardia, five (55%) patients had regional cardiac sympathetic denervation compared with zero of nine control patients with a structurally normal heart (p = 0.029). Five patients underwent right ventricular radiofrequency ablation for ventricular tachycardia, and sympathetic denervation was adjacent to the ablation site in one of these patients.nnnCONCLUSIONSnPatients with ventricular tachycardia in the absence of coronary artery disease have abnormal cardiac sympathetic innervation detectable by cardiac sympathetic scintigraphy. The role of regional cardiac sympathetic denervation in arrhythmogenesis remains to be determined.

Five-year follow-up of 589 patients treated with amiodarone

Between 1977 and 1986, 589 patients (age, 57 +/- 13 years; 464 men and 125 women) received amiodarone for ventricular fibrillation (VF; 147 patients), sustained (VT-S; 242 patients) or nonsustained (VT-NS; 80 patients) ventricular tachycardia, or supraventricular tachycardia (SVT; 120 patients). Mean left ventricular ejection fraction was 36 +/- 17%, with 23% in New York Heart Association functional class I, 49% in class II, 25% in class III, and 3% in class IV. Sixty-two percent had ischemic heart disease. Follow-up was 32 +/- 27 months (mean +/- SD). Life table analysis revealed that patients with VF, VT-S, and VT-NS had a cumulative incidence of sudden death of 9% at 1 year, increasing by about 3% per year. By years 2 and 5, the cumulative incidence of sudden death, VF, or VT-S recurrence was 26% and 38% and the percent of patients still taking amiodarone was 54% and 32%. For patients with SVT at years 2 and 5, the cumulative incidence of sudden death was 1% and 3%, and of sudden death or SVT recurrence the cumulative incidence was 20% and 29%. The percent of patients still taking amiodarone was 67% and 43%. Of 14 clinical variables assessed, New York Heart Association functional class was the best predictor of sudden death and arrhythmic failure and no other variable added independent predictive power. Older age and lower left ventricular ejection fraction were independent predictors of drug failure (sudden death or arrhythmic failure or need to discontinue amiodarone because of side effects). We conclude that despite its side effect profile, amiodarone is an effective and reasonably well-tolerated antiarrhythmic drug.

Subthreshold conditioning stimuli prolong human ventricular refractoriness

This study tested whether a subthreshold stimulus (Sc) inserted before a premature stimulus prolonged the right ventricular effective refractory period in humans, and whether the degree of effective refractory period lengthening was influenced by heart rate, Sc current intensity or Sc pulse duration. Sc at current intensity 10 mA and pulse width 2 ms prolonged mean effective refractory period from 255 ms to 277 ms (p less than 0.001, n = 20). The increase in effective refractory period was similar in 6 patients studied at pacing cycle lengths 600 (259 to 289 ms) and 400 ms (236 to 258 ms). When Sc current intensities were varied at 2, 5 or 10 mA at a constant pulse duration of 100 ms the effective refractory period progressively prolonged by 6, 40 and 81 ms respectively (p less than 0.02, n = 6). The pulse duration of Sc at a constant current of 10 mA significantly influenced effective refractory period prolongation. With Sc pulse durations of 2, 10, and 100 ms the effective refractory period prolonged by 16, 33 and 66 ms respectively (p less than 0.01, n = 7). Thus, subthreshold impulses prolong the effective refractory period in human right ventricular myocardium. The prolongation of effective refractory period depended on Sc current intensity and pulse duration but was independent of heart rate at the cycle lengths tested. The use of subthreshold stimuli as antiarrhythmic therapy may be feasible in some patients.

Encainide for treatment of supraventricular tachycardias associated with the Wolff-Parkinson-White syndrome

Thirty-three patients with supraventricular tachycardia associated with the Wolff-Parkinson-White syndrome were treated with encainide for 26 months (mean). Encainide at a mean dosage of 187 mg/day abolished or markedly decreased episodes of palpitations in 24 of 33 (73%), and no patient had syncope or required cardioversion while receiving the drug. Encainide was well tolerated and was discontinued in only 2 patients because of side effects (6%). Only 1 patient (3%) had a proarrhythmic effect while taking encainide (ventricular tachycardia). Fourteen of 16 patients (88%) with atrial fibrillation continue receiving encainide. Episodes of palpitations have been abolished or markedly decreased and no patient has had syncope or required cardioversion. All 14 of these patients had either anterograde block in the accessory pathway during atrial fibrillation or greater than or equal to 75 ms increase in the shortest R to R interval formed by 2 preexcited QRS complexes. Encainide prolonged refractory periods of the atrial (p = 0.064) and ventricular (p = 0.061) muscle. It prolonged the cycle length at which 1:1 conduction of the accessory pathway in both the anterograde and retrograde directions occurred (both, p less than 0.001). Induction of atrioventricular-reciprocating tachycardia (AVRT) was prevented in 36% of patients at repeat electrophysiologic study. The AVRT cycle length increased 112 ms (mean, p less than 0.001) in those patients in whom AVRT was still inducible. The loss of delta waves recorded with the 12-lead scalar electrocardiogram during encainide therapy was a significant predictor of anterograde accessory pathway block (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Supernormal conduction in accessory atrioventricular connections

Prospective electrophysiologic evaluation of 74 patients with ventricular preexcitation revealed 4 patients who had supernormal anterograde conduction over an accessory atrioventricular pathway. In each patient, anterograde conduction over the accessory pathway was present at relatively slow sinus rates, but the accessory pathway anterograde effective refractory period was substantially prolonged. During premature atrial stimulation, a window of supernormal conduction was identified at which closely coupled atrial extrastimuli conducted over the accessory pathway, whereas longer premature intervals resulted in accessory pathway block. Causes other than supernormal conduction to explain this phenomenon, for example, phase 4 block, were unlikely in each case. Although the mechanism of supernormal conduction in humans is unknown, the electrophysiologic findings in our patients are similar to those reported in patients with supernormal conduction in the His-Purkinje system.

Prospective evaluation of a discriminant function for prediction of recurrent symptomatic ventricular tachycardia or ventricular fibrillation in coronary artery disease patients receiving amiodarone and having inducible ventricular tachycardia at electrophysiologic study

Induction of ventricular tachycardia (VT) at electrophysiologic study in patients taking amiodarone poorly predicts recurrence of VT. Consequently, a discriminant function was developed (using parameters based on retrospective data) that appeared to identify high-risk patients. These parameters included ventricular effective refractory period, corrected QT interval, initiation of a repetitive ventricular response and the mode of VT induction. In the present study these parameters were prospectively evaluated in 60 patients with coronary artery disease and sustained VT or ventricular fibrillation (VF), in whom VT was still induced at electrophysiologic study during amiodarone therapy. Thirteen patients had recurrent events (sudden death in 8 and sustained VT in 5) and 47 patients had no symptomatic arrhythmia recurrence (follow-up for 16 +/- 2 months, mean +/- standard error of the mean). The ventricular effective refractory period, corrected QT interval and presence of a repetitive ventricular response did not discriminate between patients with and without symptomatic arrhythmia recurrence. However, an easier mode of VT induction during amiodarone therapy versus control was highly predictive of arrhythmia recurrence: 9 of 13 (69%) recurrences were in this group. In contrast, only 4 of 44 (9%) patients who had either the same or harder mode of VT induction had a recurrent event. Overall, 9 of 16 (56%) patients with an easier mode of VT induction had a recurrence, including 6 of the 8 patients with subsequent sudden cardiac death. It is concluded that electrophysiologic testing during amiodarone therapy is useful to identify high-risk patients.

Transcutaneous pacing: Patient tolerance, strength-interval relations and feasibility for programmed electrical stimulation

Abstract Noninvasive transcutaneous pacing has been used successfully in situations requiring emergent ventricular pacing,1–8 and has also been used to terminate ventricular (VT) or supraventricular tachycardia in some patients.9–13 Thus, transcutaneous pacing might logically be considered a suitable noninvasive substitute for endocardial pacing during programmed electrical stimulation studies. We therefore determined the following features of transcutaneous pacing using the Zoll noninvasive temporary pacemaker (Zoll NTP, ZMI Corp.): patient tolerance, which cardiac chambers were paced, the ventricular effective refractory period (ERP) compared with that determined by endocardial pacing and feasibility for programmed electrical stimulation in patients with ventricular tachyarrhythmias.

The electrophysiologic effects of enoximone in patients with preexisting ventricular tachyarrhythmias.

Electrophysiologic and hemodynamic effects of intravenous enoximone were studied in 15 male patients, mean age 62.2 years, with New York Heart Association classes II to IV congestive heart failure (coronary artery disease in 10 and idiopathic dilated cardiomyopathy in five patients; mean ejection fraction, 0.19). All patients had spontaneous ventricular tachyarrhythmias; eight had sustained ventricular tachycardia (VT), one had ventricular fibrillation, and six had nonsustained VT. Hemodynamic and electrophysiologic parameters including VT induction were determined before and during an intravenous infusion of enoximone. The cardiac index increased (2.49 +/- 0.89 to 2.96 +/- 0.78), and the pulmonary capillary wedge pressure decreased (22.4 +/- 13.2 to 10.0 +/- 9.0) after enoximone per predefined protocol endpoints. There was a significant decrease in spontaneous sinus cycle length, corrected sinus nodal recovery time, AH interval during atrial pacing, shortest cycle length at which 1:1 atrioventricular nodal conduction occurred, and refractory periods of the atrium, ventricle, and atrioventricular node. Enoximone did not alter the cycle length of induced VT, and there was no consistent change in the number of extrastimuli required for VT induction. A baseline 24-hour ECG recording was obtained on 14 patients (while receiving a long-term antiarrhythmic drug regimen, if needed) and repeated after 1 week and 1 month of oral enoximone therapy. There was no significant increase in the number of premature ventricular complexes per hour or VT episodes per 24 hours after 1 week or 1 month of therapy with enoximone. However, if four patients who received amiodarone and may not yet have reached steady state were excluded from analysis, there was a significant increase in the frequency of premature ventricular complexes per hour 1 month after initiation of enoximone. We conclude that intravenous enoximone reduces pulmonary capillary wedge pressure and increases cardiac output in most patients. Intravenous enoximone in doses sufficient to have hemodynamic effects shortens atrial, ventricular, and atrioventricular nodal refractoriness and decreases AV nodal conduction time but has no consistent effect on VT induction or VT cycle length. The frequency of spontaneous ventricular ectopy may increase in some patients after oral enoximone, but its clinical significance is undefined. Enoximone may be administered cautiously to patients with congestive heart failure and preexisting ventricular tachyarrhythmias.

Electrophysiologic and antiarrhythmic effects of oral encainide in patients with atrioventricular nodal reentry or nodoventricular reentry

Three patients with drug-resistant atrioventricular (AV) nodal reentrant tachycardia and two patients with reciprocating tachycardia associated with nodoventricular pathways received oral encainide after a control drug-free electrophysiologic study. In one patient with AV nodal reentry, encainide prolonged anterograde AV nodal conduction, produced complete ventriculoatrial (VA) block, and prevented tachycardia induction. Encainide had no effect on AV or VA conduction in the second patient with AV nodal reentry, and tachycardia with similar cycle length was still induced. The third patient was not studied while receiving encainide, but spontaneous AV nodal reentrant tachycardia occurring multiple times daily was abolished. In both patients with nodoventricular pathways, anterograde AV nodal and VA conduction were prolonged by encainide and tachycardia was no longer inducible. Two patients with AV nodal reentry were given long-term encainide therapy and have been free of recurrent arrhythmias for 16 and 30 months. One patient with a nodoventricular pathway has been without arrhythmia recurrence after 73 months of encainide therapy; the other patient required addition of propranolol to encainide because of recurrent tachycardia. We conclude that encainide can prolong anterograde AV nodal and VA conduction and prevent induced and spontaneous tachycardia in some patients with drug-resistant and highly symptomatic AV nodal or nodoventricular reentry.

Characteristics of Ca2+ -activated K+ channels isolated from the left ventricle of a patient with idiopathic long QT syndrome

Abstract Early afterdepolarizations (EADs), possibly caused by reduced K + conductance, have been hypothesized to cause the long QTU interval and ventricular tachyarrhythmias (VT) in patients with the long QT syndrome (LQTS). In a 26-year-old woman with aborted sudden death as a consequence of the idiopathic LQTS, we recorded with a contact electrode left ventricular endocardial EADs that were enhanced by epinephrine and phenylephrine. Because of uncertain efficacy and side effects achieved with β-adrenoceptor blockade, the patient underwent left-sided cardiac sympathectomy, at which time we obtained left ventricular biopsy tissue. Crude membrane vesicles were prepared from this tissue and single-channel activity was studied after incorporation of the vesicles in an artificial lipid bilayer (phosphatidylserine, phosphatidylethanolamine, 4:5 weight ratio in decane) in the tip of a patch clamp pipette. Bath and pipette contained 100 mmol/L KCl and 25 mmol/L N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid (HEPES) at pH 7.4. We recorded K + conducting channels with a mean slope conductance of 49.9 ± 4.7 picosiemens (pS) ( n = 5). Channel open probability was increased by the addition of 1 to 10 μmol/L Ca 2+ to the experimental chamber. Addition of charybdotoxin (1–3 nmol/L), a known specific inhibitor of Ca 2+ -activated K + channels, blocked channel activity. These results are the first to demonstrate Ca 2+ -activated K + -channels from a patient with idiopathic LQTS. These channels appear to show normal characteristics when studied in an artificial planar lipid bilayer.