Efficacy and safety of medium- and high-dose diltiazem alone and in combination with digoxin for control of heart rate at rest and during exercise in patients with chronic atrial fibrillation

We evaluated the efficacy and the safety of medium-(240 mn/day) and high-dose (360 mg/day) diltiazem alone and in combination with digoxin when used for control of heart rate in 12 patients with chronic atrial fibrillation. Medium-dose diltiazem was comparable to therapeutic dose of digoxin at rest (88 +/- 19 vs 86 +/- 12 beats/min) but superior during peak exercise (154 +/- 23 vs 170 +/- 20 beats/min; p less than .05). High-dose diltiazem resulted in better control of heart rate than digoxin both at rest (79 +/- 17 beats/min; p less than .05) and exercise (136 +/- 25 beats/min; p less than .05) but was associated with side effects in 75% of the patients. Combined therapy of digoxin and diltiazem enhanced the effect of digoxin alone and resulted in significantly better control of heart rate at rest (67 +/- beats/min with medium-dose and 65 +/- beats/min with high-dose diltiazem) and during peak exercise (132 +/- 32 and 121 +/- 24 beats/min, respectively). However, the difference in heart rate between these two doses was not significant. Reduction of heart rate combined with concomitant effect on blood pressure resulted in a significant fall in pressure-rate product at rest from 10,077 +/- 1708 mm Hg/min on digoxin alone to 7877 +/- 1818 mm Hg/min after the addition of medium-dose diltiazem (p less than .05) and during exercise form 25,670 +/- 3606 to 18,439 +/- 4115 mm Hg/min (p less than .05). Continued therapy with digoxin combined with diltiazem 240 mg/day for 21 +/- 8 days in nine patients showed persistent effect on heart rate and blood pressure without any toxic manifestations or change in serum digoxin (1.5 +/- 0.4 vs 1.3 +/- 0.4 ng/ml) or plasma diltiazem concentrations (204 +/- 72 vs 232 +/- 129 ng/ml). In conclusion, medium-dose diltiazem when combined with digoxin is an effective and safe regimen for the treatment of patients with chronic atrial fibrillation and enhances digoxin-mediated control of heart rate both at rest and during exercise.     

Relationships between heart rate, exercise tolerance and cardiac output in atrial fibrillation: the effects of treatment with digoxin, verapamil and diltiazem

Six patients with chronic atrial fibrillation (AF) took singledoses of digoxin, verapamil and diltiazem, alone and in combination.Three hours after dosing, resting and post-exercise heart rate,exercise tolerance and resting and post-exercise cardiac outputwere measured. Post-exercise heart rates ranged from 167 bpm(after placebo) to 122 bpm (after digoxin plus diltiazem) (P<0.05).However, the lower ventricular rates seen after treatment withthe calcium antagonists were not assciated with improved exercisetolerance, which did not differ significantly between the varioustreatments. Reduction of the ventricular rate was associatedwith a small increase in stroke volume but the benefits of thiswere offset by a rate related reduction in cardiac output. Furtherreduction of the rapid ventricular rates seen in digitalizedpatients with AF does not appear to be of benefit in terms ofimproving either exercise tolerance or cardiac output.     

Efficacy of oral diltiazem to control ventricular response in chronic atrial fibrillation at rest and during exercise

Although digoxin is often the first choice for control of ventricular response in chronic atrial fibrillation, it fails to slow exercise rates. Diltiazem, a calcium channel antagonist that slows atrioventricular conduction, was administered to 16 patients who failed to achieve adequate rate control on low level exercise testing despite digoxin therapy. Therapeutic response to diltiazem was assessed with submaximal and maximal exercise tests and 24 hour ambulatory electrocardiographic monitoring. During the diltiazem treatment phase, ventricular response at rest diminished (96 +/- 17 versus 69 +/- 10 beats/min, p less than 0.001) as did rate during submaximal exercise (155 +/- 28 versus 116 +/- 26, p less than 0.001), maximal exercise (163 +/- 14 versus 133 +/- 26, p less than 0.001) and average ventricular response during 24 hour monitoring (87 +/- 13 versus 69 +/- 10, p less than 0.001). Rate at rest decreased 26 +/- 15% and submaximal exercise rate diminished 24 +/- 12%. Thirteen (81%) of the 16 patients exhibited at least 15% slowing of rate at rest and during submaximal exercise. Eleven patients (69%) reported alleviation of symptoms. There was no change in serum digoxin levels during diltiazem treatment (1.3 +/- 0.5 versus 1.3 +/- 0.6 ng/ml, p = NS). On withdrawal of diltiazem, ventricular response returned to baseline values. Diltiazem is an effective agent for control of ventricular response, both at rest and during exercise, in digoxin-treated patients with chronic atrial fibrillation.     

A comparison of digoxin, diltiazem and their combination in the treatment of atrial fibrillation

Fourteen patients (four females) with chronic atrial fibrillationwere entered into a randomized, double-blind crossover studyto compare the effects of treatment with diltiazem alone, digoxinalone, and a combination of diltiazem plus digoxin. The doseof digoxin was adjusted so as to achieve serum concentrationswithin the range 1.3–2.6 nmoll^–1 between six andeight hours after dosing. Four patients were withdrawn fromthe study; three patients experienced side effects while takingdiltiazem and one reverted to sinus rhythm while taking digoxin.Among the remaining 10 patients, mean heart rates were significantlylower during treatment with the combination of digoxin and diltiazemthan with digoxin alone both at rest, after exercise and duringambulatory ECG monitoring. Post-exercise heart rates were reducedby 15% with combination therapy when compared with digoxin alone(151.9 vs. 128.1 bpm), but there was no evidence that this reductionin ventricular rate was associated with improved exercise tolerance.The results suggest that further reduction of the rapid ventricularrates seen in digitalized patients with AF by the use of diltiazemdoes not appear to be of benefit in the majority of patients.     

Effects of a high dose intravenous bolus amiodarone in patients with atrial fibrillation and a rapid ventricular rate

BACKGROUND: Amiodarone, given as intravenous bolus has not yet been studied in patients with atrial fibrillation and a high ventricular rate. METHODS: One hundred consecutive patients with atrial fibrillation and a ventricular rate above 135 bpm were randomized to receive either 450 mg amiodarone or 0.6 mg digoxin given as a single bolus through a peripheral venous access. If the ventricular rate exceeded 100 bpm after 30 min, another 300 mg amiodarone or 0.4 mg digoxin were added. Primary endpoints of the study were the ventricular rate and the occurrence of sinus rhythm after 30 and 60 min. Secondary endpoints were blood pressure during the first hour after drug administration, and safety regarding drug induced hypotension, and phlebitis at the infusion site. RESULTS: Baseline heart rate was 144+/-19 in the amiodarone group and 145+/-15 in the digoxin group (p=0.72). Following amiodarone, heart rate was 104+/-25 after 30 min compared to 116+/-23 in the digoxin group (p=0.02) and 94+/-22 versus 105+/-22 after 60 min (p=0.03). After 30 min, sinus rhythm was documented in 14 (28%) patients following amiodarone compared to 3 (6%) patients in the digoxin group (p=0.003), and after 60 min in 21 (42%) versus 9 (18%) patients (p=0.012). Asymptomatic hypotension was observed in 4 amiodarone treated patients, and superficial phlebitis in 1 patient. CONCLUSIONS: Amiodarone, given as an intravenous bolus is relatively safe and more effective than digoxin for heart rate control and conversion to sinus rhythm in patients with atrial fibrillation and a rapid ventricular rate.     

Dynamic electrocardiogram in chronic atrial fibrillation treated with digitalis

To assess heart rate variability in chronic atrial fibrillation, 60 patients (20 men, 40 women: mean age 63 +/- 8 years: NYHA 2.0 +/- 0.5) with various cardiac conditions were investigated with 24-hour Holter monitoring during daily life. Twenty-five healthy subjects (5 men, 20 women: mean age 55 +/- 9) were considered as the control group. All patients had "controlled" heart rate (50-90 bpm) on basal ECG, normal hematological and thyroid hormone values, and took digoxin alone (mean dosage 0.22 +/- 0.05 mg). Mean digoxin plasma levels were 0.88 +/- 0.48 ng/ml. Maximum, minimum and average heart rate were quite good during the night but too high during the daytime and far higher than those observed in healthy subjects. In fact, up to 82% of patients (at 9 a.m.) had a maximum heart rate higher than 115 bpm. Pauses between 2.0 and 3.0 sec occurred in 40 out of 60 patients (66%). No patients had pauses longer than 4.0 sec. In our experience, patients in chronic atrial fibrillation "controlled" with digoxin alone showed a daytime heart rate which was often too high. We suggest 24-hour Holter monitoring to detect subgroups that may be treated successfully with digoxin associated with calcium-antagonists or beta-blockers.     

Effects of diltiazem in supraventricular paroxysmal tachyarrhythmias

Diltiazem (0.3 mg/kg body weight intravenous in 2 minutes) was administered to 40 patients (24 males, 16 females, mean age 51.55 years) with paroxysmal supraventricular tachyarrhythmias: 7 patients with atrial fibrillation, 6 patients with atrial flutter, 25 patients with paroxysmal supraventricular tachycardia, 2 patients with uncommon atrioventricular reciprocating tachycardia. In patients with atrial fibrillation intravenous diltiazem produced a significant decrease of ventricular response (from 160 +/- 11 to 113.57 +/- 10.34--p less than 0.01). In patients with atrial flutter intravenous diltiazem produced variable effects: an increase in atrio-ventricular block (from 2:1 to 3:1 atrio-ventricular conduction (2 patients); conversion to sinus rhythm (1 patient); change to atrial fibrillation (1 patient); no appreciable change of the basic rhythm (2 patients). In paroxysmal supraventricular tachycardia patients conversion to sinus rhythm occurred in 20/22 patients (91%) treated with intravenous diltiazem (mean conversion time 4.69 minutes). In the 2 patients with uncommon atrioventricular nodal reciprocating tachycardia diltiazem increased P'-R and R-P' intervals without appreciable change of the basic rhythm. No serious side effects from drug administration were noted. Intravenous diltiazem appears to be as a highly effective medication in conversion or control of paroxysmal supraventricular tachyarrhythmias.     

Short-term control of supraventricular tachycardia with verapamil infusion and calcium pretreatment

Nineteen consecutive patients with atrial fibrillation/flutter or other types of supraventricular tachycardia were given intravenous (IV) calcium salts (1 g) followed by verapamil infusion at a rate of 1 mg/min. Successful treatment was defined as control of ventricular response to less than or equal to 100 beats per minute (bpm) or conversion to sinus mechanism in patients with atrial arrhythmias: 11 patients had atrial fibrillation; three had atrial flutter; four had reentrant supraventricular tachycardias (SVT); and one had paroxysmal SVT. Therapy was successful in all patients. The mean dose of verapamil required to achieve desired outcome was 20 mg. Heart rate showed no significant change as a result of calcium pretreatment (160 bpm v 151 bpm). However, heart rate was significantly decreased, to 95 bpm, after treatment with verapamil. Blood pressure showed no change from baseline with either calcium or verapamil therapy. Verapamil infusion following IV calcium successfully treats atrial fibrillation/flutter or SVTs without depressing systemic blood pressure.     

静脉应用地尔硫卓和美托洛尔治疗老年心功能衰竭伴心房颤动快速心室率的疗效和安全性比较

目的比较在中重度心功能衰竭伴心房颤动快速心室率的老年患者静脉注射地尔硫卓和美托洛尔控制心室率的有效性和安全性。方法采用随机单盲方法,将72例中重度心功能衰竭伴心房颤动快速心室率的老年患者分为2组,分别给予地尔硫卓和美托洛尔静脉注射,观察有效率及血压、症状和体征变化。结果地尔硫卓组有效率为94.6%,用药前心室率为149±26次/min、用药后120min降至97±19次/min,下降幅度为35%;美托洛尔组有效率为97.1%,用药前后心室率分别为150±27、95±18次/min,下降幅度为37%。两组血压均有下降但多在正常范围,地尔硫卓组无心功能恶化,美托洛尔组1例心功能恶化。结论静脉注射地尔硫卓和美托洛尔均能有效地控制老年中重度心功能衰竭患者的心房颤动快速心室率,且相对安全。     

The effect of diltiazem, a calcium channel-blocking drug, on cardiac rate and rhythm in hyperthyroid patients

Tachycardia and tachyarrhythmias are frequent in patients with thyrotoxicosis, especially in the elderly. Since myocardial calcium uptake is increased in thyrotoxic rats, the efficacy of the calcium channel-blocking drug diltiazem in decreasing heart rate and the incidence of arrhythmias was evaluated in 11 hyperthyroid patients. All patients were studied with a 24-hour Holter monitor prior to the beginning of sole diltiazem therapy (120 mg given every eight hours), on the tenth day of therapy, and five days after therapy was discontinued. Heart rate significantly decreased by 17% during diltiazem treatment (96.5 +/- 3.7 systoles/min vs 79.9 +/- 3.2 systoles/min [mean +/- SE]) and returned to baseline values five days after the therapy was discontinued (100.7 +/- 3.4 systoles/min). Similarly, the number of premature ventricular extrasystoles per hour was significantly decreased (18 +/- 7 vs 2 +/- 1). In three patients, asymptomatic bouts of supraventricular tachycardia, paroxysmal atrial fibrillation, or ventricular tachycardia disappeared during diltiazem therapy. These findings suggest that calcium-blocking drugs may be extremely useful as adjunctive therapy for thyrotoxicosis in the presence of angina, congestive failure, and tachyarrhythmias.     

A prospective, randomized controlled trial comparing the efficacy and safety of sotalol, amiodarone, and digoxin for the reversion of new-onset atrial fibrillation

STUDY OBJECTIVE: A prospective, randomized controlled trial of new-onset atrial fibrillation was conducted to compare the efficacy and safety of sotalol and amiodarone (active treatment) with rate control by digoxin alone for successful reversion to sinus rhythm at 48 hours. METHODS: We prospectively randomly assigned 120 patients with atrial fibrillation of less than 24 hours' duration to treatment with sotalol, amiodarone, or digoxin using a single intravenous dose followed by 48 hours of oral treatment. Patients had ECG monitoring for 48 hours, and time of reversion, adequacy of rate control, and numbers of adverse events were compared. After 48 hours, those still in atrial fibrillation underwent cardioversion according to a standardized protocol. After 48 hours of therapy and attempted cardioversion, the number of patients whose rhythms had successfully reverted were compared. RESULTS: There was a significant reduction in the time to reversion with both sotalol (13. 0+/-2.5 hours, P <.01) and amiodarone (18.1+/-2.9 hours, P <.05) treatment compared with digoxin only (26.9+/-3.4 hours). By 48 hours, the active treatment group was significantly more likely to have reverted to sinus rhythm than the rate control group (95% versus 78%, P <.05; risk ratio 5.4, 95% confidence interval [CI] 1.5 to 19.2 ). In those patients whose rhythms did not revert to sinus rhythm, there was superior ventricular rate control in the sotalol group at both 24 and 48 hours compared with those who received either amiodarone or digoxin. There were also fewer adverse events in the active treatment group compared with the rate control group. CONCLUSION: Immediate pharmacologic therapy for new-onset atrial fibrillation with class III antiarrhythmic drugs (sotalol or amiodarone) improves complication-free 48-hour reversion rates compared with rate control with digoxin.     

Does atrial overdrive pacing prevent paroxysmal atrial fibrillation in paced patients?

The role of atrial overdrive pacing for the suppression of paroxysmal atrial fibrillation remains unclear. To investigate this we have performed a randomised study evaluating the role of an increased atrial base rate in suppressing this arrhythmia in patients implanted with a permanent pacemaker (Chorum ELA) for sick sinus syndrome with previous documented paroxysmal atrial fibrillation. Twenty-seven patients (mean age, 69; 15 female) were randomised to two 3-month single-blinded crossover periods of DDDR pacing. The pacemaker was set with a base rate of 60 bpm (normal) during one period and at 10 bpm (overdrive) above the average heart rate during the other, mean (S.D.) 75+/-7 beats/min (range, 70-96). The fallback algorithm of the pacemaker was activated to record the number and duration of paroxysmal atrial fibrillation episodes. During the overdrive period there was a significant increase in the total duration of atrial pacing (normal 60+/-26% vs. overdrive 72+/-28%, P<0.001). However there was no significant difference in the number of paroxysmal atrial fibrillation episodes (normal 43+/-109 vs. overdrive 43+/-106, P=ns), or their total duration (normal 42+/-108 h vs. overdrive 99+/-254 h, P=ns). In conclusion, atrial overdrive pacing, achieved by increasing the atrial base rate, has no incremental benefit in the suppression of paroxysmal atrial fibrillation when compared to rate responsive pacing with a base rate of 60 bpm.     

Effect of diltiazem and metoprolol on left atrial appendix functions in patients with nonvalvular chronic atrial fibrillation.

OBJECTIVES: Thrombo-embolic events are the important cause of mortality and morbidity in patients with chronic atrial fibrillation (CAF). The origin of thromboembolism is often the left atrial appendix (LAA). Flow rate velocity (FRV) inside the LAA is the major determinant of thrombus formation. The aim of our study was to investigate the effects of diltiazem and metoprolol used for ventricular rate control on FRV of the LAA in CAF patients and thus to evaluate the positive or negative effects of these two drugs on thromboembolic events. METHODS: Sixty-four patients were included in the study. All patients were suffering from CAF for more than a year. The patients were allocated to two groups according with agent used for rate control- metoprolol (Group 1; n=31) and diltiazem (Group 2; n=33). Transesophageal echocardiography was applied to all patients and LAA FRV was measured by a pulse wave Doppler in the 1/3 proximal portion of the LAA. The measurements were repeated after applying 5 mg metoprolol to Group 1 and 25 mg diltiazem to Group 2 via venous cannula. RESULTS: In Group 1 after metoprolol LAA flow velocity changed from 0.25 +/- 0.90 m/s to 0.25 +/- 0.10 m/s (p>0.05). In group 2 after diltiazem left atrial appendix FRV decreased from 0.21 +/- 0.9 m/s to 0.19 +/- 0.6 m/s (p>0.05). CONCLUSIONS: In patients with CAF metoprolol used for ventricular rate control had no effect on LAA flow velocity and the observed decrease in LAA flow rate velocity with intravenous diltiazem was insignificant.     

Effects of diltiazem, propranolol, and their combination in the control of atrial fibrillation.

The effect of the combined treatment with propranolol 20 mg tid and diltiazem 60 mg tid in patients with chronic atrial fibrillation treated with digoxin was evaluated. Thirteen patients entered a double-blind, three-phase crossover study. Heart rate was significantly reduced during rest and at maximal exercise (p less than 0.05) during combined treatment compared with treatment with any single drug. No significant changes in maximal work load, exercise time, systolic blood pressure at maximal work load, or subjective sensation of well-being could be demonstrated during combined drug treatment. The RR distribution pattern was unaffected by the addition of propranolol, diltiazem, or their combination to the chronic digoxin treatment. It is concluded that the combination of diltiazem and propranolol has no advantages over any of these drugs singly, in the moderation of heart rate in patients with atrial fibrillation even combined with basic digitalis treatment, and that the intrinsic AV nodal function is unaffected by these drugs or their combination.     

Pharmacokinetics and pharmacodynamics of intravenous diltiazem in patients with atrial fibrillation or atrial flutter.

BACKGROUND. Diltiazem, a calcium channel blocker, has been shown to be safe and effective in the treatment of patients in atrial fibrillation and/or atrial flutter. However, there have been no pharmacokinetic/pharmacodynamic studies of diltiazem in these patients. METHODS AND RESULTS. The pharmacokinetics and pharmacodynamics of intravenous diltiazem were determined in 32 patients with atrial fibrillation or atrial flutter (mean +/- SD age, 66 +/- 7 years; mean baseline heart rate, 131 +/- 10 beats per minute) after 20 mg or 20 mg followed by 25-mg bolus doses and a 10 and 15 mg/hr infusion for 24 hours. After the 10 and 15 mg/hr infusions of diltiazem, mean +/- SD elimination half-life was 6.8 +/- 1.8 and 6.9 +/- 1.5 hours, volume of distribution was 411 +/- 151.8 and 299 +/- 70.8 I, and systemic clearance was 42 +/- 12.4 and 31 +/- 8.3 l/hr, respectively. Percentages of the plasma concentrations of the principal metabolites desacetyldiltiazem and N-desmethyldiltiazem to diltiazem were < 15% and < 10%, respectively. Thirty of 32 patients maintained response throughout the 24-hour infusion of diltiazem. Using a sigmoidal Emax pharmacodynamic model, a strong relation (mean +/- SD r2, 0.78 +/- 0.2) was observed between plasma diltiazem concentration and percent heart rate reduction. Mean +/- SD Emax (maximum percent reduction in heart rate from baseline) and EC50 (plasma diltiazem concentration that achieves half Emax) were 52 +/- 17% and 110 +/- 84 ng/ml, respectively. The model predicts that mean plasma diltiazem concentration of 79, 172, and 294 ng/ml are required to produce a 20%, 30%, and 40% reduction in heart rate, respectively. A relation between plasma diltiazem concentration and percent change in systolic blood pressure (SBP) or diastolic blood pressure (DBP) from baseline was not observed (mean +/- SD r2, SBP/DBP: 0.35 +/- 0.24/0.36 +/- 0.2). There were no untoward side effects observed. CONCLUSIONS. First, the pharmacokinetics of diltiazem in patients with atrial fibrillation or atrial flutter is nonlinear with an apparent dose-dependent decrease in systemic clearance with increasing infusion rate. Second, using a sigmoidal Emax model, there is a strong relation between plasma diltiazem concentration and percent heart rate reduction. Third, the plasma concentrations of the principal metabolites desacetyldiltiazem and N-desmethyldiltiazem are low and are not expected to contribute significantly to the pharmacodynamics of intravenous diltiazem in these patients.     

Ventricular rate control in chronic atrial fibrillation during daily activity and programmed exercise: a crossover open-label study of five drug regimens

OBJECTIVESWe compared the effects of five pharmacologic regimens on the circadian rhythm and exercise-induced changes of ventricular rate (VR) in patients with chronic atrial fibrillation (CAF).BACKGROUNDSystematic comparison of standardized drug regimens on 24 h VR control in CAF have not been reported.METHODSIn 12 patients (11 male, 69 ± 6 yr) with CAF, the effects on VR by 5 standardized daily regimens: 1) 0.25 mg digoxin, 2) 240 mg diltiazem-CD, 3) 50 mg atenolol, 4) 0.25 mg digoxin + 240 mg diltiazem-CD, and 5) 0.25 mg digoxin + 50 mg atenolol; were studied after 2 week treatment assigned in random order. The VR data were analyzed by ANOVA with repeated measures. The circadian phase differences were evaluated by cosinor analysis.RESULTSThe 24-h mean (±SD) values of VR (bpm) were − digoxin: 78.9 ± 16.3, diltiazem: 80.0 ± 15.5, atenolol: 75.9 ± 11.7, digoxin + diltiazem: 67.3 ± 14.1 and digoxin + atenolol: 65.0 ± 9.4. Circadian patterns were significant in each treatment group (p < 0.001). The VR on digoxin + atenolol was significantly lower than that on digoxin (p < 0.0001), diltiazem (p < 0.0002) and atenolol (p < 0.001). The time of peak VR on Holter was significantly delayed with regimens 3 and 5 which included atenolol (p < 0.03). During exercise, digoxin and digoxin + atenolol treatments resulted in the highest and lowest mean VR respectively. The exercise Time-VR plots of all groups were nearly parallel (p = ns). The exercise duration was similar in all treatment groups (p = ns).CONCLUSIONSThis study indicates that digoxin and diltiazem, as single agents at the doses tested, are least effective for controlling ventricular rate in atrial fibrillation during daily activity. Digoxin + atenolol produced the most effective rate control reflecting a synergistic effect on the AV node. The data provides a basis for testing the effects of chronic suppression of diurnal fluctuations of VR on left atrial and ventricular function in CAF.     

Ventricular rate control and exercise performance in chronic atrial fibrillation: effects of diltiazem and verapamil

The effects of two calcium channel blockers, diltiazem (270 mg/day) and verapamil (240 mg/day), were studied in 18 patients with chronic atrial fibrillation. During 24 h Holter electrocardiographic monitoring, mean ventricular rate (beats/min) decreased from 88 +/- 14 with placebo to 76 +/- 13 (p less than 0.001) with diltiazem and 80 +/- 11 (p less than 0.01) with verapamil. Maximal symptom-limited exercise tolerance (W) increased from 127 +/- 39 during the placebo period to 136 +/- 42 (p less than 0.01) with diltiazem and 137 +/- 39 (p less than 0.01) with verapamil. Ventricular rate and rate-pressure product were lower at rest and during exercise with diltiazem and verapamil than with placebo (p less than 0.001), with the drugs being similarly effective. Ventricular rate at maximal exercise (beats/min) was 179 +/- 13 with placebo compared with 159 +/- 21 with diltiazem and 158 +/- 23 with verapamil. Maximal oxygen uptake (ml/kg per min) was 22.3 +/- 4.5 with placebo, 23.7 +/- 4.9 (p less than 0.05) with diltiazem and 22.9 +/- 4.5 with verapamil (p = NS). Respiratory gas exchange anaerobic threshold was reached at a work load (W) of 76 +/- 21 with placebo, 84 +/- 27 (p less than 0.05) with diltiazem and 85 +/- 23 (p less than 0.01) with verapamil. In conclusion, patients with chronic atrial fibrillation have modestly improved exercise tolerance with calcium channel blockade therapy. The dromotropic responses and the effects on physical performance are of similar magnitude for diltiazem and verapamil.     

静脉注射不同剂量盐酸地尔硫卓治疗快室率心房纤颤的观察

目的:探讨静脉应用不同剂量地尔硫卓治疗快速心房纤颤的临床疗效和安全性。方法:100例快速心房纤颤(排除预激综合征合并房颤)患者,设对照组(18例),研究组按地尔硫卓0.05mg/kg(20例)、0.15mg/kg(22例)、0.25mg/kg(22例)、0.35mg/kg(18例)四种不同剂量于3min内静脉注射,观察用药时、后患者心率、血压、心电图及临床症状。结果:不同剂量地尔硫卓对快速心房纤颤作用随剂量增加而增大,以0.25mg/kg显效率最大(90.9%),较0.05mg/kg组、0.15mg/kg组显著(P分别<0.01,<0.05),且起效时间短,临床症状明显改善(P<0.01);血压随剂量增加而逐渐下降。未发生严重副作用,无一例发生房室传导阻滞和窦性停搏。结论:静脉注射地尔硫卓可以迅速控制心房纤颤的心室率,疗效以0.25mk/kg为最佳,安全可靠。     

On the possibility of amiodarone use in some cases of persistent atrial fibrillation

Aim of the study was to investigate mechanisms of amiodarone action on atrial and ventricular rhythm during persistent atrial fibrillation (PAF), and to assess efficacy of amiodarone as monotherapy or in combination with digoxin. Holter ECG monitoring and registration of high resolution ECG with construction of periodograms of ff waves and histograms of RR intervals (MATLAB 5.3 environment) were carried out in 34 patients (mean age 63.1+/-11.0 years) with PAF. Amiodarone (550.0+/-143.4 mg/day), digoxin (0.30+/-0.09 mg/day) with amiodarone (571.4+/-106.9 mg/day) were given for 21 days with recordings of high resolution ECG at baseline and on day 21. Long term therapy (1.7 years) with combination of digoxin 0.19+/- 0.07 mg/day) and amiodarone (254+/-82.0 mg/day) was controlled by Holter ECG monitoring. Monotherapy with amiodarone was not associated with significant lowering of heart rate (HR) (small er, Cyrillic=0.054) because of complex effect of amiodarone of HR: significant increase of period of ff waves (by 0.031+/-0.011 s), with facilitation of their conduction to ventricles combined with significant 0.10+/-0.08 s increment of minimal RR. Amiodarone combined with digoxin caused significantly lesser (by 0.009+/-0.017 s) enlargement of ff waves and significant lowering of HR (by 21.24+/-15.77 bpm) at the account of slowing of AV conduction (minimal RR increased by 0.12+/-0.08 s) and suppression of early RR peaks (0.28-0.46 s). The combination effectively suppressed tachysystolia resistant to other therapy (maximal HR 170-215 bpm) with significant lowering of mean (by 16.5+/-13.1 bpm) and maximal (by 43.3+/-35.6 s) HR, with suppression of ventricular extrasystoles in 83% of patients, and without significant lowering of minimal HR and appearance of pauses from 3 s. Level of thyrotrophic hormone rose from 2.4 to 5/9 IU/ml (p >0.05).     

No increase in serum digoxin concentration with high-dose diltiazem

The effect of incremental diltiazem dosing during concomitant digoxin administration over a four-week period in eight healthy adult volunteers (mean age, 28 +/- 4 years) was studied. The study group received 0.25 mg of digoxin twice daily for two days, after which they received 0.25 mg daily for the duration of the study. Following baseline electrocardiographic evaluation and measurement of trough digoxin levels, all subjects received 120 mg of diltiazem daily for one week, then 240 mg daily for one week, followed by 360 mg daily for one week. Resting electrocardiographic parameters (heart rate, P-R interval), renal function, electrolyte values, and digoxin and diltiazem concentrations were measured weekly. Daily administration of 360 mg of diltiazem plus 0.25 mg of digoxin resulted in a significant decrease in heart rate (from 68 +/- 9 beats per minute to 61 +/- 10 beats per minute; p less than 0.05), a marginal increase in P-R interval (from 169 +/- 22 msec to 179 +/- 21 msec; p = 0.08), and no significant change in trough serum digoxin concentration (from 0.85 +/- 0.08 ng/ml to 0.90 +/- 0.08 ng/ml; p = NS). The administration of up to 360 mg of diltiazem per day with 0.25 mg of digoxin per day was not associated with significant increases in serum digoxin concentrations in healthy subjects.