THERAPY AND PREVENTION Termination of paroxysmal supraventricular tachycardia with a single oral dose of diltiazem and propranolol

The efficacy of a single oral dose combination of 120 mg diltiazem and 160 mg propranolol in terminating paroxysmal supraventricular tachycardia (PSVT) was evaluated in 15 patients. All 15 patients underwent electrical induction of PSVT that lasted longer than 15 min, and all underwent randomized crossover placebo and diltiazem and propranolol studies on 2 consecutive days. On each day PSVT was induced and placebo or diltiazem and propranolol was administered 15 min later. Electrical conversion of PSVT was performed when severe symptoms occurred or at the end of 240 min. With placebo PSVT lasted 164 + 89 (mean + SD) min; four patients had spontaneous conversion. With diltiazem and propranolol PSVT lasted 39 + 49 min (p < .001); 14 patients had spontaneous conversion in an average of 27 + 15 min. None of the 14 patients had electrical reinduction of sustained PSVT after conversion. The sinus nodal recovery time during spontaneous or electrical conversion of PSVT was 911 + 459 msec with placebo and 1076 + 270 msec with diltiazem and propranolol (NS). Two patients developed transient second-degree atrioventricular block and junctional rhythm while on diltiazem and propranolol. Serum diltiazem and propranolol levels (ng/ml) after diltiazem and propranolol in five patients were, respectively, 49 + 26 and 108 101 at 15 min, 232 ± 147and228 + 148 at30min, 254 ± 169and370 + 393 at45min, 280 + 115 and209 + 189 at 60 min, 188 ± 72 and 268 -+ 264 at 120 min, and 118 + 57 and 265 + 148 at 240 min. Follow-up study after 5.6 ± 0.9 months revealed 51 spontaneous episodes of PSVT in the patient group; 50 of the 51 episodes were converted after the single oral dose of the diltiazem and propranolol combination, with a conversion time of 21 + 16 min. In conclusion, a single oral dose combination of diltiazem and propranolol effectively terminates acute episodes of PSVT and may be considered the therapeutic regimen of choice in selected patients. Circul,ation 71, No. 1, 104-109, 1985. PAROXYSMAL supraventricular tachycardia (PSVT) that fails to convert to sinus rhythm with simple vagal maneuvers is usually terminated by parenteral drug administration. The prophylaxis of recurrent PSVT is dependent on long-term administration of antiarrhythmic drugs. Margolis et al. ' used intermittent drug therapy in which antiarrhythmic medication was taken only at the onset of an episode of tachycardia. This approach was effective in terminating both supraventricular and ventricular tachyarrhythmias in 24 of 32 patients and obviated some of the need for hospitalization and long-term drug treatment. They, however, did not systematically evaluate the efficacy of a specific therapeutic regimen in terminating a specific type of From the Section of Cardiology, Department of Medicine., Chang Gung Memorial Hospital, Taipei, Taiwan. Address for correspondence: Delon Wu. M.D., Chang Gung Memorial Hospital, 199 Tung Hwa North Rd., Taipei 105, Taiwan. Received June 22, 1984; revision accepted Sept. 27, 1984. 104 tachycardia. Since most paroxysmal tachycardias convert spontaneously to sinus rhythm without intervention, the efficacy of a specific therapy cannot be determined without a strictly controlled comparison. The present study was undertaken to define the efficacy of a single oral dose of a combination of diltiazem and propranolol in terminating acute episodes of PSVT. Our results suggest that this approach may be the therapy of choice in most patients with PSVT. Materials and methods Patient selection. The study group consisted of 15 patients (1 1 men and four women) ranging in age from 19 to 52 years (mean + SD 34 + 10). Of these 15 patients, two had atrioventricular nodal reentrant tachycardia, and 13 had atrioventricular reentrant tachycardia utilizing a retrogradely conducting accessory pathway. Of the former two patients. one had the slow-fast form, and the other the fast-slow form of atrioventricular nodal reentrant tachycardia. Of the latter 13 patients, eight had ventricular preexcitation and five had a concealed accessory pathCIRCULATION by gest on A uust 7, 2017 http://ciajournals.org/ D ow nladed from THERAPY AND PREVENTION-ARRHYTHMIA way. The average frequency of PSVT was 11 ± 15 episodes/ year. Previous drug regimens that failed to control the arrhythmia satisfactorily included digoxin in seven patients, propranolol in two patients, combination of digoxin and propranolol in two patients, diltiazem in three patients, verapamil in four patients, quinidine in four patients, and disopyramide in two patients. All 15 patients underwent electrical induction of sustained PSVT that lasted longer than 15 min. Electrophysiologic study. Each patient gave informed written consent. Cardiac medications were discontinued for at least five plasma half-lives before the study. A No. 7F quadripolar electrocatheter was percutaneously introduced into the right femoral vein, advanced to the right atrium, and positioned across the tricuspid valve. The proximal two electrodes were used for His bundle recording and the distal two electrodes for right ventricular pacing. A second No. 7F hexapolar electrocatheter was introduced into the right antecubital vein by a small incision and advanced to the right atrium and then to the coronary sinus. The distal two electrodes were used to record the left atrial electrogram from the coronary sinus, the middle two electrodes were used to record the right atrial electrogram, and the proximal two electrodes were used to stimulate the right atrium. The distal two electrodes of the hexapolar electrocatheter as well as the quadripolar electrocatheter were also positioned at different sites in the coronary sinus and the right atrium to map the atrial activation sequence during induced episodes of PSVT. Multiple surface and intracardiac electrograms were simultaneously recorded on a multichannel oscilloscopic recorder (Electronics for Medicine VR16) at a paper speed of 100 mm/ sec. Stimuli were provided by a programmable digital stimulator (DTU PC 100, Bloom and Associates) and were approximately twice the diastolic threshold and 2 msec in duration. As previously described, conduction intervals and anterograde and retrograde refractory periods were measured and defined by incremental pacing and extrastimulus testing.'2 The diagnoses of atrioventricular nodal reentrance and atrioventricular reentrance were made according to the previously described criteria.2 Anterograde weak link of the reentrant circuit refers to termination of echoes or PSVT occurring with an atrial response not followed by a ventricular response. Retrograde weak link of the reentrant circuit refers either to termination of echoes or tachycardia occurring with a ventricular response not followed by an atrial response, or to achievement of an atrioventricular interval that is longer than the control critical atrioventricular interval without induction of atrial echoes or PSVT. After the control studies the quadripolar electrode catheter was removed while the hexapolar electrode catheter was withdrawn from the coronary sinus, advanced to the right ventricle, and secured for subsequent electrophysiologic studies. The proximal two electrodes of the hexapolar catheter were kept at the junction of the superior vena cava and the right atrium, as during the control study. The distal two electrodes were used for ventricular pacing during subsequent electrophysiologic studies. Study protocol. After the initial electrophysiologic study, PSVT was electrically induced and allowed to continue for 15 min while each patient was observed. After the observation period each patient underwent a randomized crossover trial with placebo or a single oral dose combination of 120 mg diltiazem and 160 mg propranolol on 2 consecutive days. To enhance absorption, the placebo or the combination of diltiazem and propranolol was crushed into powder form and given orally with water. Electrocardiographic tracings were recorded continuously on a tape recorder for 240 min after intervention. Electrical termination of PSVT was performed only when severe symptoms occurred or at the end of 240 min. Sinus nodal recovery time during spontaneous or electrical termination of PSVT was Vol. 71, No. 1, January 1985 measured as the interval from the last QRS complex during PSVT to the first sinus P wave after conversion. Blood pressure and heart rate were taken every 15 min for the first hour and every 30 min thereafter. In five patients multiple blood samples were taken for measurements of serum diltiazem and propranolol concentrations. The serum diltiazem concentration was measured by the thin-layer chromatography3 (Tanabe Seiyaku Co, Ltd.; Osaka, Japan). The serum propranolol concentration was measured by a high-performance liquid chromatographic procedure.4 The study protocol was reviewed and approved by the Subcommittee on Human Research of the Chang Gung Memorial Hospital. Data analysis. Data are expressed as mean + SD and were analyzed with the paired Student t test, the chi-square test, and analysis of variance.