Richard F. Kehoe

Extended Endocardial Resection for the Treatment of Ventricular Tachycardia and Ventricular Fibrillation

A total of 40 patients with drug-refractory, life-threatening cardiac rhythm disturbances--ventricular tachycardia in 23 patients and ventricular fibrillation in 17 patients--underwent extended endocardial resection (EER) of scar tissue. Scarring was due to myocardial infarction in 38 patients, to previous congenital heart operation in 1 patient, and to sarcoidosis of the heart in 1. The EER procedure was directed by epicardial and endocardial mapping data whenever possible, and was usually combined with revascularization, aneurysmectomy, or, in 5 patients, mitral valve replacement. Operative mortality was 10%, incident to poor preoperative ventricular function and hemorrhage secondary to previous cardiac surgical procedures. Thirty-three of the 36 survivors (92%) are free of arrhythmia at follow-up periods ranging from 3 to 36 months (mean, 12.5 months); the arrhythmia in the remaining 3 patients is now drug controlled. Thirty-three patients had postoperative electrophysiological studies, and in 30 (91%), the arrhythmia was no longer inducible. The results of surgical treatment for ventricular tachycardia and ventricular fibrillation were similar. The results also proved satisfactory whether the EER procedure was directed by visual observation or mapping.

Chronic nonparoxysmal sinus tachycardia in otherwise healthy persons.

Seven patients had chronic, unexplained, nonparoxysmal sinus tachycardia. The clinical, electrocardiographic, and electrophysiologic characteristics of these cases are described. In each case electrocardiographic and electrophysiologic observations suggested that tachycardia was nonparoxysmal and due to increased automaticity of the sinus node (or of an automatic atrial focus located very near the sinus node). The mechanisms of increased sinus node automaticity in these patients were explored using drugs affecting the autonomic nervous system. In each patient these studies suggested a defect in either sympathetic or vagal nerve control of resting heart rate, with or without an abnormality of intrinsic heart rate. Data are also presented on baroreceptor reflex arc function in these patients.

Amiodarone in Patients with Previous Drug-Mediated Torsade de Pointes: Long-Term Safety and Efficacy

The safety and efficacy of long-term amiodarone therapy were examined in 12 patients who had previously developed torsade de pointes as a complication of previous antiarrhythmic therapy. The QTc intervals were determined at the time of torsade de pointes (570 +/- 40 ms), after 7 days of amiodarone loading (490 +/- 70 ms), and after 3 months of chronic amiodarone administration (580 +/- 80 ms). Compared to a drug-free control period, QTc was significantly prolonged (P less than 0.05) at the time of torsade de pointes, after amiodarone loading, and after 3 months of amiodarone therapy. The QTc intervals at the time of torsade de pointes and after chronic amiodarone treatment were not significantly different. At 16 +/- 7 months of follow-up, all patients remained free of subsequent torsade de pointes, syncope, or sudden death. In addition, 5 of 6 patients with a history of sustained ventricular tachycardia remained free from arrhythmic recurrence despite persistence of inducible ventricular tachycardia during programmed stimulation studies done before discharge. We conclude that amiodarone can often be used safely and effectively in patients who have previously had an episode of drug-mediated torsade de pointes. Amiodarone-induced QTc prolongation, even when marked, does not predict recurrent torsade de pointes. These observations also suggest that the propensity for a drug to produce this arrhythmia is dependent on other electrophysiologic effects in addition to its ability to simply lengthen repolarization.

Effects of procainamide on atrioventricular nodal re-entrant paroxysmal tachycardia

SUMMARYElectrophysiological effects of 750 mg i.v. procainamide were studied in 14 patients with dual pathway atrioventricular (A-V) nodal re-entrant paroxysmal tachycardia (PSVT). All patients utilized an A-V nodal slow pathway for antegrade and an A-V nodal fast pathway for retrograde conduction during PSVT. In all 14 patients, procainamide depressed retrograde fast pathway conduction, manifest by increase in mean ± SEM ventricular paced cycle length (CL) producing V-A block from 5 295 ± 25 to 385 ± 17 msec (P < 0.001). Antegrade fast and slow pathway properties were unchanged with procainamide.Eleven of the 14 patients had induction of sustained PSVT before procainamide. Eight of these lost ability to induce or sustain PSVT after procainamide, reflecting depression of retrograde fast pathway conduction with either absence of atrial echoes (4 pts) or induction of nonsustained PSVT, with termination of PSVT occurring after QRS (retrograde block in fast pathway) (4 pts). In three of these 11 patients, sustained PSVT was inducible before and after procainamide (mean CL of 395 ± 38 and 395 ± 40 respectively) (NS).Three patients had induction of nonsustained PSVT before procainamide. In two, induction of sustained PSVT occurred after procainamide due to enhanced antegrade slow pathway conduction, while in the other PSVT remained nonsustained.In conclusion, procainamide inhibited induction of sustained A-V nodal re-entrant PSVT in most patients, reflecting selective depression of retrograde A-V nodal fast pathway conduction. In a minorityof patients, vagolytic effects of procainamide potentiated induction of sustained PSVT.

Ventricular tachycardia induced by biventricular pacing in patient with severe ischemic cardiomyopathy.

Introduction: Cardiac resynchronization therapy (CRT) is a new alternative which affords symptomatic improvement in two‐thirds of patients who exhibit medically refractory congestive heart failure (CHF) as well as significant prolongation of the QRS duration (>135 msec). As more experience with CRT accrues, unexpected complications of this promising therapy may become apparent. Herein, we describe a patient with severe ischemic cardiomyopathy and refractory CHF who developed incessant ventricular tachycardia (VT) after the initiation of biventricular pacing.

Antiarrhythmic efficacy of N-acetylprocainamide in patients with premature ventricular contractions.

Oral administration ofa 1.5‐gm dose of N‐acetylprocainamide (NAPA) to 9 patients with premature ventricular contractions (PVCs) confirmed previous indirect evidence that this metabolite of procainamide has antiarrhythmic efficacy and potency comparable to those of procainamide. Although the mechanism by which NAPA acts as an antiarrhythmic drug is not known, it was found that the 6 patients with coupled PVCs responded to NAPA therapy and that the 3 patients without coupled PVCs failed to respond. Coupling interval prolongation also occurred during NAPA therapy in 4 of the 6 responding patients. These observations suggest that NAPA may terminate coupled PVCs by slowing and then interrupting conduction of re‐entrant impulses, as has been proposed for procainamide. NAPA plasma concentrations of 7.4–17.2 f,μg/ml were well tolerated by the patients and produced an average fall of 3 mm Hg in mean arterial pressure and a 7.6% mean increase in corrected QT interval.

Safety and efficacy of sotalol in patients with drug-refractory sustained ventricular tachyarrhythmias

The safety and efficacy of oral sotalol, an investigational beta-adrenergic blocker with class III antiarrhythmic drug properties, were examined in a multicenter study in 236 patients with sustained ventricular tachyarrhythmias. In 104 patients, the index arrhythmia was a cardiac arrest, and all patients had undergone at least 3 previous unsuccessful antiarrhythmic trials (mean = 5 per patient). In the 106 patients assessed by programmed electrical stimulation, sotalol completely suppressed induction of ventricular tachycardia (VT) in 33 (31%) and rendered VT slower (greater than 100 ms prolongation of cycle length) or more difficult to induce in 29 (27%). Using continuous 24-hour ambulatory monitoring methods, sotalol complete- and partial-response rates were 51 and 12%, respectively. Of the 236 acute-phase patients, 151 were discharged receiving long-term sotalol therapy. The median sotalol dose was 480 mg/day. At a mean follow-up of 346 +/- 92 days, 27 patients (18%) had recurrence of sustained arrhythmia; 9, sudden death; 11, sustained VT; 5, automatic defibrillator discharge; and 2, syncope. Adverse effects forced discontinuation of therapy in 10 patients (7%): 6 secondary to symptomatic bradyarrhythmia, 2 due to refractory heart failure, 1 due to torsades de pointes, and 1 from bronchospasm. Life-table analysis of sotalols overall long-term efficacy at 6, 12 and 18 months were 80, 76 and 72%, respectively. Although mean follow-up was short (less than 1 year), neither acute-phase programmed stimulation nor 24-hour ambulatory monitoring responses were significantly predictive of subsequent arrhythmic outcome. Proarrhythmia was documented in 18 patients (7%), 17 during the acute phase and 1 during long-term follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Safety and efficacy of oral sotalol for sustained ventricular tachyarrhythmias refractory to other antiarrhythmic agents

The safety and efficacy of oral sotalol were evaluated in 481 patients with drug-refractory sustained ventricular tachyarrhythmias (VT) in an open-label multicenter study. After drug-free baseline evaluations, therapy was initiated at 80 mg every 12 hours, with upward dose titrations of 160 mg/day being allowed at intervals of 72 hours to a maximum dose of 480 mg every 12 hours. Efficacy determinations were made by either programmed electrical stimulation (PES) or Holter monitoring responses. Of the 481 patients enrolled, 473 underwent acute-phase titration. Of the 269 patients assessable by PES, 94 (34.9%) exhibited complete response (suppression of inducible VT), with an additional 67 patients (24.9%) exhibiting partial response. Of the 109 patients assessable by Holter monitoring, 43 (39.4%) exhibited a complete response. There were no significant differences between responders and nonresponders with regard to left ventricular ejection fraction. Although response rates tended to improve as the sotalol dose was increased to 640 mg/day, efficacy was most commonly achieved at a sotalol dose of 320 mg/day. Sotalol was discontinued because of adverse effects in 42 (8.9%) of the acute-phase patients. The most common adverse effect was proarrhythmia, which was observed in 23 patients (4.9%). Proarrhythmia took the form of torsades de pointes in 12 patients and an increase in VT episodes in 11. In 3 acute-phase patients (0.6%), sotalol was discontinued because of the emergence of congestive heart failure. A total of 286 patients entered the long-term phase. Life-table estimates of the proportion of patients who remained free of recurrence of arrhythmia at 12, 18, and 27 months were 0.76, 0.72, and 0.66, respectively. There were no significant differences in time to recurrence of arrhythmia as related to PES response, Holter monitor response, baseline left ventricular ejection fraction, or history of congestive heart failure. Among the 70 patients (24.5%) in whom there was recurrence of arrhythmia, sudden death occurred in 17 and sustained VT in 41. Sotalol was discontinued owing to presumed adverse effects in 21 (7.3%) of the long-term patients, including 8 with proarrhythmia; proarrhythmia consisted of torsades de pointes in 3 patients and increased episodes of VT in 5. These findings suggest that sotalol is an effective drug for the long-term treatment of patients with drug-refractory sustained VT. Proarrhythmia was observed in only 6.4% of the study population and tended to occur during the acute titration phase. The need to discontinue therapy because of congestive heart failure was uncommon.(ABSTRACT TRUNCATED AT 400 WORDS)

Determinants of atrioventricular reentrant paroxysmal tachycardia in patients with Wolff-Parkinson-White syndrome.

SUMMARY Normal and anomalous pathway properties were evaluated in 50 patients with preexcitation to discover determinants of paroxysmal supraventricular tachycardia (PSVT). Twenty-eight patients had inducible PSVT and 22 had no inducible PSVT. Patients with inducible PSVT had: 1) ability for retrograde anomalous pathway conduction demonstrated with ventricular pacing at short paced cycle lengths (< 429 msec) and close coupling intervals (< 400 msec); and 2) antegrade AV nodal refractoriness less than anomalous pathway refractoriness during rapid and/or coupled atrial pacing with ability for exclusive normal pathway conduction for at least one beat at short atrial paced cycle lengths (< 375 msec) or close coupling intervals (< 320 msec).Failure to induce PSVT was accounted for by one of the following: 1) absent or poor retrograde anomalous pathway conduction alone (six patients); 2) inadequate antegrade AV nodal properties alone (eight patients); 3) both inadequate antegrade AV nodal and retrograde anomalous pathway properties (seven patients); and 4) prolonged atrial refractoriness (one patient). There were no significant differences in anomalous pathway antegrade refractory periods between the patients with and without PSVT.We conclude that the occurrence of PSVT in Wolff-Parkinson-White syndrome depends on the ability for retrograde anomalous pathway conduction and adequate antegrade AV nodal conduction. The inability to induce PSVT usually reflects inadequate retrograde anomalous and/or antegrade normal pathway properties. The ability to induce PSVT is independent of antegrade anomalous pathway properties.

Multicenter trial of sotalol compared with procainamide in the suppression of inducible ventricular tachycardia: A double-blind, randomized parallel evaluation

Sotalol is the prototype class III agent that combines beta-blocking properties with the propensity to prolong the effective refractory period by lengthening the action potential duration. Its precise effect on the prevention of ventricular tachycardia-ventricular fibrillation (VTVF) compared to class I agents has not been evaluated in a blinded study. In a double-blind parallel-design multicenter study, the electrophysiologic and antiarrhythmic effects of intravenous and oral sotalol (n = 55) and procainamide (n = 55) were therefore compared in patients with VTVF inducible by programmed electric stimulation. Sotalol produced a greater effect on lengthening the ventricular effective refractory period (VERP). It prevented the inducibility of VTVF in 30% versus 20% for procainamide, but this was not significantly different. In an alternate therapy group (n = 41) of similar patients previously refractory to or intolerant of procainamide, intravenous sotalol prevented inducibility in 32%. The pooled overall sotalol efficacy rate was 31%. There was a significant relation between the increase in the VERP and the prevention of inducibility of VTVF (n = 56; p < 0.02). VERP of > or = 300 msec was critical for the prevention of VTVF inducibility. Thirteen sotalol and 6 procainamide responders from the randomized group and 30 from the nonrandomized groups completed 1 year of oral sotalol therapy follow-up. Life-table analysis of these patient in each group showed a trend in favor of sotalol; however, statistical analysis was not possible because of the small numbers of patients. Both sotalol and procainamide were well tolerated. In the randomized group there was one case of sudden death during treatment with sotalol and two cases of nonfatal torsades de pointes in the procainamide group and two in the sotalol group; in the nonrandomized alternate therapy group, there were 6 cases of nonfatal torsades de pointes. The data support the emerging role of sotalol in the control of symptomatic ventricular tachycardia and fibrillation.