A multicentre, double-blind randomized crossover comparative study on the efficacy and safety of dofetilide vs sotalol in patients with inducible sustained ventricular tachycardia and ischaemic heart disease.

BACKGROUND: Antiarrhythmic drugs are still used for the treatment of ventricular tachyarrhythmias, in combination with implantable cardioverter-defibrillators or without them. AIM OF THE STUDY: In a double-blind randomized crossover design, the short- and long-term efficacy and safety of oral dofetilide or oral sotalol were compared in 135 patients with ischaemic heart disease and inducible sustained ventricular tachycardia. METHODS: The inducibility of ventricular tachycardia was determined by programmed electrophysiological stimulation at baseline. Patients were then blindly randomized to receive either oral dofetilide 500 microg twice daily or oral sotalol 160 mg twice daily, for 3 to 5 days. Suppression of inducible ventricular tachycardia on the drug was then assessed by programmed electrophysiological stimulation. After a wash-out period of at least 2.5 days, the patients received the alternative treatment for 3 to 5 days. Suppression of inducible ventricular tachycardia on the alternate drug was again determined by programmed electrophysiological stimulation. Selection of long-term treatment was allocated blindly according to programmed electrophysiological stimulation results. RESULTS: During the acute phase, 128 patients received both dofetilide and sotalol. Sixty-seven patients were responders to either drug. Forty-six patients (35.9%) were responders to dofetilide compared with 43 (33.6%) to sotalol (P=ns). Only 23 patients responded to both dofetilide and sotalol. Adverse events, deemed to be treatment related, were seen in 2.3% of patients receiving dofetilide and 8.6% of patients receiving sotalol (P=0.016). Three patients on dofetilide had torsade de pointes. Two patients receiving sotalol died during the acute phase (one was arrhythmic death, and the other was due to heart failure). During the long-term phase, two of 42 patients (4.8%) receiving dofetilide and three of 27 patients (11.1%) receiving sotalol withdrew from treatment due to lack of efficacy. Overall, during the long-term phase, 23.8% of the patients receiving dofetilide and 37.0% of the patients receiving sotalol, withdrew from treatment with a similar pattern of withdrawals for the two drugs. CONCLUSION: Dofetilide was as efficacious as sotalol in preventing the induction of sustained ventricular tachycardia. There was no concordance in the response rate in two-thirds of the patients. Dofetilide was significantly better tolerated during the acute phase than sotalol. Both dofetilide and sotalol were well tolerated during the long term with no statistically significant difference in the adverse events.

Adrenergic effects on reentrant ventricular rhythms in subacute myocardial infarction.

BACKGROUND: Reentry has been shown to be a mechanism of ventricular arrhythmias elicited by programmed premature stimulation in the subacute ischemic period of dogs subjected to myocardial infarction. The spatial distribution of refractoriness in these hearts has been shown to play an important part in the formation of functional arcs of conduction block during programmed ventricular stimulation. Because the adrenergic nervous system influences cardiac arrhythmias and myocardial infarction can directly affect sympathetic innervation in the heart, we investigated the role of the sympathetic nervous system on reentry in the canine heart 4 days after infarction. METHODS AND RESULTS: The influences of adrenergic stimuli on the initiation of reentrant ventricular excitation were studied using a 128-channel computerized recording system in the canine heart 4 days after ligation of the left anterior descending coronary artery. Bilateral stimulation of the ansae subclavia preferentially improved conduction of premature beats in the normal zones. This corresponded to an improvement in excitability, as measured by a decrease in stimulus strength at the same premature coupling interval as control. Consequently, the effective refractory period was preferentially shortened at normal sites but not at ischemic sites. Both of these changes contributed to a shift of the arc of functional conduction block toward more normal tissue. As a result, sites proximal to the arc of functional conduction block had more time to recover excitability and thereby were available to be reexcited by the distal activation wave front. Conversely, intravenous infusion of norepinephrine preferentially shortened the effective refractory period of sites in the ischemic zone, thereby indicating that denervation hypersensitivity had occurred at these sites. The spatial dispersion of refractoriness and the arc of functional conduction block were significantly reduced in size. As a consequence, previously inducible reentrant rhythms were no longer inducible. CONCLUSIONS: Sympathetic stimulation can be considered an arrhythmogenic intervention, whereas norepinephrine infusion may be considered antiarrhythmic in this experimental model.

Dofetilide, a novel class III antiarrhythmic agent.

Dofetilide is a potent and selective class III antiarrhythmic agent that is under development for the treatment of re-entrant tachyarrhythmias (ventricular tachycardia/ventricular fibrillation, atrial fibrillation/atrial flutter, and paraoxysmal supraventricular tachycardia). In animal studies, dofetilide selectively inhibits the rapid component of the time-dependent outward potassium current (IKr) and therefore increases the effective refractory period and action potential duration without affecting the fast inward sodium current. Studies in dogs have shown that dofetilide (a) prolongs the effective refractory period in a dose-dependent manner, (b) elevates ventricular fibrillation threshold, (c) facilitates conversion of electrically induced ventricular fibrillation or fibrilloflutter to sinus rhythm, (d) does not influence conduction within the His-Purkinje system or within the myocardium, (e) does not impair cardiac contractility, and (f) reduces dispersion of ventricular repolarization. Dofetilide has been administered to healthy volunteers as well as to patients with ischemic heart disease or with supraventricular arrhythmias; the compound has generally been well tolerated. Side effects have occasionally been reported, but have generally been transient and mild and occur in placebo-treated subjects as well. No clinically significant changes in laboratory safety tests have been detected. The pharmacokinetic profile of dofetilide both in healthy volunteers and patients includes a linear dose-plasma concentration relationship and also a linear plasma concentration-QTc relationship. The terminal plasma elimination half-life is approximately 9-10 h and systemic bioavailability in the region of 100%. The elimination pattern is balanced, with 50% being excreted unchanged via the kidney, the remaining 50% being metabolized in the liver to inactive metabolites, with greater than 90% of circulating drug-related material being unchanged dofetilide. After intravenous administration of the compound, a slight hysteresis in the plasma drug level-QTc relationship has been detected. Pharmacodynamic data demonstrate dose- and concentration-dependent effects on myocardial repolarization as evidenced by prolongations of the QTc interval. This is reflected in significant prolongations in the effective and functional refractory periods and monophasic action potential duration throughout the myocardium. No effects on sinus node function, conduction parameters, or cardiac contractility have been detected in any of the clinical studies, supporting the contention that dofetilide is a highly selective class III antiarrhythmic agent.

The electrophysiological effects of flosequinan.

We have evaluated the acute electrophysiological effects of flosequinan in 18 patients with normal ventricular function. Following intravenous infusion of flosequinan 100 mg over 1 h, mean (SD) systolic blood pressure fell from 131 +/- 19 to 120 +/- 22 mmHg (P less than 0.02) and there was significant shortening of sinus cycle length (732 +/- 151 to 575 +/- 93 ms, P less than 0.001), AH interval (110 +/- 45 to 71 +/- 19 ms, P less than 0.01), QRS duration (98 +/- 28 to 91 +/- 26 ms, P less than 0.02) and QT interval (373 +/- 47 to 337 +/- 35 ms, P less than 0.001), but no change in sinus node recovery time, intra-atrial conduction time, HV interval or the corrected QTc interval. There was a reduction in both anterograde atrioventricular Wenckebach cycle length (299 +/- 53 to 259 +/- 52 ms, P less than 0.01) and retrograde ventriculoatrial Wenckebach cycle length (375 +/- 77 to 300 +/- 56 ms, P less than 0.01). There was no change in atrial or ventricular effective refractory period (ERP) but atrial functional refractory period (FRP) shortened (233 +/- 31 to 212 +/- 24 ms, P = 0.07) as did ventricular FRP (249 +/- 24 to 234 +/- 21 ms, P less than 0.01). Patients received an oral dose of flosequinan 50 mg 12 h later. By 24 h, sinus cycle length, QRS duration and the QT interval had all returned towards baseline values, but ventricular ERP had lengthened (199 +/- 22 to 215 +/- 26 ms, P less than 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of postural changes versus exercise on the electrophysiologic parameters of the accessory pathway.

The electrophysiologic profile of the accessory pathway was studied in 17 patients (mean age +/- standard deviation 32 +/- 14 years) with Wolff-Parkinson-White (WPW) syndrome who were either lying down in a supine position, standing, or undergoing isometric or dynamic treadmill exercise. There were significant decreases in the PP interval after isometric exercise, standing and dynamic exercise (supine 764 +/- 224, standing 638 +/- 146, isometric 605 +/- 170, treadmill 455 +/- 86 ms; p less than 0.05). Both anterograde and retrograde accessory pathway refractory periods were measured after a constant drive of 400 ms during lying down supine, standing and isometric and treadmill exercise (Bruce protocol stage II). There was no significant decrease in the anterograde accessory pathway refractory period during isometric exercise (lying down 265 +/- 22 to isometric exercise 256 +/- 13 ms, p less than 0.05), but there were significant decreases (p less than 0.05) during standing (246 +/- 24 ms) and treadmill exercise (235 +/- 17 ms). The retrograde accessory pathway refractory period also showed a significant decrease (supine 272 +/- 16, isometric 267 +/- 23, standing 249 +/- 15, treadmill 237 +/- 17 ms; p less than 0.05). The relative change in refractory periods was greater when patients changed from lying down to standing than when they changed from standing to treadmill exercise, despite obvious higher adrenergic neuronal activities during exercise. These findings suggest that testing the accessory pathway during free standing can give a reliable indication of the sensitivity of the accessory pathway to sympathetic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Myopotential interference in unipolar rate responsive pacemakers.

The effects of myopotential interference on unipolar rate responsive pacemakers were assessed in 22 patients. Six types of pacemakers (from four manufacturers) were studied: five TX2 (QT sensing), seven Biorate (five RDP3 and two MB-1, respiratory rate sensing), seven Activitrax (activity sensing), two Medtronic 2503 (dP/dt sensing), and one Sensolog P703 (activity sensing). Provocative tests using arm exercises were performed in both VVI and rate responsive modes. At nominal sensitivity settings (1.8-2.5 mV), 55% of these patients were myopotential positive for at least 1 provocative test. Pressing the palms together was found to be the most sensitive provocative test. Rate response was achieved with treadmill exercise (all patients), hyperventilation (RDP3 and MB-1) and tapping (Activitrax) or wobbling the pacemaker in its pocket (Sensolog). During continued rate acceleration, myopotential interference was induced by arm exercises. The duration of inhibition was shorter when the provocative tests were performed during rate response compared to that occurred at rest. Short periods of myopotential interference resulted in temporary inhibition of pacing but rate response continued immediately on removal of the interference. In one patient with a RDP3 pacemaker, a prolonged episode of myopotential interference during treadmill exercise resulted in reversion of the pacemaker to the interference mode. Appropriate adjustment of the sensitivity setting effectively controlled the symptoms in most patients. However, one patient with a QT sensing pacemaker and symptomatic myopotential interference required programming to the VVT pacing mode. Two out of five patients with RDP3 required pacemaker replacement because of uncontrolled myopotential interference.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of exercise performance of six rate-adaptive right ventricular cardiac pacemakers.

Single chamber cardiac pacemakers capable of automatically adjusting the rate according to body requirements have become an important means of physiologic pacing in patients with bradycardias. Such pacemakers are dependent on a nonatrial sensor of physiologic needs to optimize the rate response. Fifty rate-adaptive right ventricular pacemakers were implanted in 46 patients with a mean age of 60 +/- 4 years (mean +/- standard error of the mean). There were 2 types of activity-sensing pacemakers (Activitrax and Sensolog 702), the QT-sensing pacemakers (TX2 and Quintech), 2 types of respiratory-sensing pacemakers (Biorate [RDP3 and MB1] and Meta) and a rate-adaptive pacemaker that senses right ventricular dP/dt (Deltatrax). The rate responses of a group of 9 volunteers of similar age (62 +/- 2 years) were also included for comparison. Improvement in exercise duration in the rate-adaptive mode compared to the constant-rate ventricular pacing (VVI) mode was achieved during randomized symptom-limited treadmill exercise (from 26 to 49%). Compared with the sinus responses, the activity-sensing pacemakers responded most appropriately in speed. However, their rate responses were not related to workload and had lower correlations with estimated oxygen consumption (r = 0.7 and 0.47 for Activitrax and Sensolog, respectively). Respiratory-sensing pacemakers responded more appropriately in magnitude (r greater than 0.8) although their rate responses were slower. All pacemakers studied either showed no response or a reverse-rate response to the Valsalva maneuver. It is concluded that the currently available rate-adaptive ventricular pacemakers improve exercise performance compared with VVI pacemakers in patients with bradycardias.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of 50 Hz external electrical interference on implanted cardiac pacemakers.

The effects of injected 50 Hz alternating current on the function of cardiac pacemakers has been observed in 18 patients with implanted unipolar VVI units. Current, in the range 0-600 microA was applied via electrodes attached to the patients' upper body and feet and fed from a specially designed current injection unit at the bedside. Most implanted pacemakers reverted to interference mode in the current range 29-250 microA. At current levels just below the reversion current all units developed irregular and inappropriate pacing. This current level was pacemaker dependent and varied in the range 27-246 microA. The total reversion current depended on the location of the injecting electrodes and on the patients' posture. The sensitivity of the units to injected interference was increased by deep inspiration. Temporary pacing catheters fitted to an additional ten patients were used to monitor the interference voltage which would be sensed by an implanted unit. This voltage was similarly dependent on patient posture and on deep respiration. Current injection has proved to be a safe, controllable and reproducible method of testing the sensitivity of implanted pacemakers to 50 Hz external interference.

Rate modulation by arm movements of the respiratory dependent rate responsive pacemaker.

The rate response to arm movements of the respiratory dependent rate responsive pacemaker (RDP3, Biotec) was assessed in four patients implanted with this pacemaker. The pacemaker was implanted in the left prepectoral region and the auxiliary impedance measuring electrode positioned subcutaneously over the right second intercostal space with its tip lateral to the mid-clavicular line. The lower rate of the pacemaker was programmed to 75 bpm. While holding the breath, swinging arm movements (30 times) resulted in rate acceleration. The peak rate was faster when the arm on the side of the auxiliary electrode was swung (mean +/- SEM, 117 +/- 8 compared to 130 +/- 5 bpm, P less than 0.5). The mean rate response of the subjects to brief treadmill exercise (Bruce stage I) performed with both hands holding the support rails, swinging the right arm only, swinging left arm only and swinging both arms were 108, 140, 135 and 128 bpm respectively. Impedance measurement confirmed the significant influence of arm movements on thoracic "impedance" changes, which was mainly caused by electrode motion artifacts affecting the two electrode measuring system. This effect was dependent on the relative positions of the impedance measuring electrodes (i.e., between the pacemaker casing the auxiliary lead). Subsequently the auxiliary lead of the respiratory pacemaker (MB-1, and Biorate) was implanted in the lower part of the chest on the right sternal edge in another patient. Rate acceleration was only observed when the arm on the side of the pacemaker was swung. As arm movements often accompany physical activities, pacing rate can be affected and should be considered when programming this pacemaker.

Clinical cardiac electrophysiologic evaluation of the positive inotropic agent, DPI 201-106.

DPI201-106 is a new positive inotropic agent. The cardiac electrophysiology of 16 patients was studied before and during DPI 201-106 administration (loading dose of intravenous DPI 201-106, 1.8 mg kg-1 h-1 administered over 10 min, followed by a maintenance dose of 0.2 mg kg-1 h-1). DPI 201-106 had no effect on the sinus node. The AH interval during fixed-rate atrial pacing became prolonged during DPI 201-106 infusion. There was a significant prolongation of the QT interval [QT (corrected), 417 +/- 22 to 502 +/- 35 ms, P less than 0.05; QT (atrial pacing at 600 ms), 374 +/- 17 to 419 +/- 23 ms, P less than 0.05; QT (ventricular pacing at 600 ms), 409 +/- 37 to 449 +/- 30 ms, P less than 0.05]. The ventricular effective refractory period significantly prolonged during DPI 201-106 administration (242 +/- 21 to 287 +/- 56 ms, P less than 0.05), but the supernormal-period duration decreased. The atrial effective refractory period was shortened in four patients and prolonged in one (261 +/- 67 to 240 +/- 53 ms, NS). The corrected atrial repolarization time (PTac) shortened significantly during DPI 210-106 infusion (479 +/- 26 to 445 +/- 22 ms at 20 min of the maintenance dose, P less than 0.05). Atrial fibrillation was initiated in five patients during DPI infusion, but no ventricular arrhythmia was provoked. These findings suggest that DPI 201-106 has novel differential electrophysiological effects on atria and ventricles.

Pacing techniques in the prophylaxis of junctional reentry tachycardia.

Atrial premature beats (APBs) which encounter sufficient AV delay may initiate junctional reentry tachycardia (JRT). This form of initiation may be prevented by rendering part of the reentry circuit refractory by artificial stimulation following an APB which would otherwise initiate JRT. Two such approaches have been suggested: preexcitation pacing, that is, ventricular stimulation with a short AV delay triggered by atrial depolarization; and preemptive pacing, which consists of early atrial stimulation coupled to the initiating APB. We compared these approaches and describe them as follows. Ten patients with JRT (six with atrioventricular reentry and four with AV nodal reentry) were studied. Against a background of regular atrial drive, the range of coupling intervals over which a stimulated APB initiated JRT (tachycardia initiation window) was determined (control). The tachycardia initiation window was also measured when a second atrial stimulus followed the initiating APB 20 ms after atrial recovery (preemptive pacing) or when a ventricular stimulus closely followed the initiating APB with an AV delay of 65 ms (preexcitation pacing). The tachycardia initiation window in response to an isolated APB was also assessed following regular AV pacing with a short (65 ms) AV delay (preconditioning pacing) and the effect of preexcitation pacing following the initiating APB was also assessed after a similar drive (combined preconditioning and preexcitation pacing). All protocols were performed at two basic drive cycle lengths. The results are arranged for the slow and fast drives, respectively, and were as follows: control initiating windows--49.5, 28.5 ms; preemptive pacing initiation windows--151, 38 ms; preexcitation pacing initiation windows--26, 23.5 ms; preconditioning pacing initiation windows--45.5, 35 ms; combined preconditioning and preexcitation pacing initiation windows--10.0, 2.5 ms. Whereas preemptive pacing tended to widen the tachycardia initiation windows (a proarrhythmic effect) the combination of preconditioning and preexcitation pacing considerably reduced the possibility of JRT initiation by an atrial premature beat.

Rapid autonomic tone regulation of atrioventricular nodal conduction in man.

The changes in P-P intervals and atrioventricular nodal (AVN) conduction during the Valsalva maneuver were studied in 17 patients. In spite of a significant decrease in the sinus P-P interval during phase II of the maneuver (733 +/- 143 to 520 +/- 86 msec, p less than 0.005) and prolongation during phase IV (884 +/- 171 msec, p less than 0.01), there was no change in the AH interval (control: 78 +/- 15: phase II: 76 +/- 15: phase IV: 72 +/- 14 msec, N.S.). In six patients consecutive P-P intervals during phase II were recorded in solid-state memory and were used to trigger pacing of the high right atrium at rest. This showed a significant increase in the AH interval (75 +/- 10 to 123 +/- 45 msec, p less than 0.05). Valsalva maneuver during constant rate atrial pacing resulted in a significant decrease in the AH interval during phase II (115 +/- 36 to 80 +/- 15 msec, p less than 0.001). During phase IV there was prolongation of the AH interval (156 +/- 58 msec) but in 11 patients (61%) a variable degree of Wenckebach periodicity appeared. Thus autonomic tone modulates the changes in AVN conduction induced during physiologic heart rate variation, resulting in maintenance of adequate 1:1 AVN conduction.

Efficacy of incremental doses of tiapamil on exercise performance in patients with chronic stable angina pectoris.

Ten patients with chronic stable angina were treated with 4 incremental doses of tiapamil (200 mg, 400 mg, 600 mg and 800 mg) in a double-blind, placebo-controlled study. Treadmill exercise electrocardiograms were performed before and after single oral doses of tiapamil. A dose-dependent increase in exercise duration occurred after tiapamil with significant improvement after tiapamil 600 mg and 800 mg. Mean exercise duration increased from 327 +/- 41 seconds (control) to 399 +/- 49 seconds (P less than 0.01) after tiapamil 600 mg and from 314 +/- 39 seconds (control) to 416 +/- 49 seconds after tiapamil 800 mg, P less than 0.001. There was an associated improvement in mean exercise time to onset of 1 mm ST-segment depression from 240 +/- 41 seconds (control) to 300 +/- 48 seconds in 10 patients after tiapamil 600 mg, (P less than 0.02) and from 206 +/- 35 seconds (control) to 272 +/- 51 seconds in 9 patients after tiapamil 800 mg, P less than 0.01. Two patients were free of angina and 1 patient normalized his ST-segments after tiapamil 800 mg. Dose-dependent side-effects were mild and tolerable. Tiapamil is safe and highly effective in improving exercise tolerance and relieving myocardial ischaemia in patients with chronic stable angina.

Clinical cardiac electrophysiology of indoramin, a post-synaptic alpha blocker.

Indoramin is a selective post-synaptic alpha blocker. Animal experiments had shown that it has antiarrhythmic effects, but whether this is due to its alpha blocking effect or some other mechanism is not known. Fifteen patients (10 males) underwent electrophysiological investigations before and 15 minutes after intravenous indoramin injection (0.2-0.5 mg kg-1). The plasma level of indoramin was measured and the patients were divided into two groups: group 1 (8 patients) whose plasma level was less than 100 micrograms ml-1 (average 72 micrograms ml-1) and group 2 (7 patients) whose plasma level was more than 100 micrograms ml-1 (average 151 micrograms ml-1). In both groups there was a significant drop in the systolic blood pressure after indoramin (129 +/- 22 to 111 +/- 23 mmHg, P less than 0.001). There was a marked improvement in the sinus node recovery time in group 1 only (253 +/- 92 to 163 +/- 40 ms, P less than 0.01). Similarly there was a decrease in AH interval during fixed rate atrial pacing in group 1 only (128 +/- 33 to 100 +/- 37 ms, P less than 0.05) and a significant decrease in the Wenckebach cycle length after indoramin in group 1 only (372 +/- 85 to 347 +/- 74 ms, P less than 0.05). At the atrial level there were no significant effects in either group but there was a significant increase in the ventricular effective refractory period in group 2 (231 +/- 35 to 264 +/- 64 ms, P less than 0.05) but no change in group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Management of ventricular arrhythmias associated with mitral valve prolapse by combined alpha and beta blockade.

Ventricular arrhythmias are common in patients with mitral valve prolapse. Ten patients with echocardiographically confirmed mitral valve prolapse and documented ventricular arrhythmias were included in this study. The aim was to assess the value of combined alpha- and beta-blockade (labetalol) compared with beta-blockade alone (propranolol) in the management of ventricular arrhythmias in these patients. The study was performed using physiological stress, such as the Valsalva manoeuvre, isometric exercise and treadmill exercise, to initiate ventricular arrhythmias before and after intravenous propranolol or labetalol and to document arrhythmias during 24 hour electrocardiography before and after oral medication. Labetalol and propranolol decreased the heart rate and blood pressure response to these manoeuvres to a similar extent but labetalol was more effective in the control of the ventricular arrhythmias. These findings suggest that alpha adrenergic receptors may play a role in the pathogenesis of the ventricular arrhythmias in mitral valve prolapse syndrome and that labetalol offers an alternative treatment for the management of this condition.

Clinical cardiac electrophysiological assessment of indoramin.

Indoramin is a selective postsynaptic alpha-adrenoceptor antagonist used for the treatment of hypertension. Animal experiments have shown that indoramin has some antiarrhythmic activity, but whether this is due to its alpha-blocking effect or some other mechanism is not known. Fifteen patients (10 men) underwent electrophysiological investigations before and 15 min after intravenous indoramin injection (0.20-0.50 mg/kg). The plasma level of indoramin was measured and the patients were divided into two groups: group I (eight patients), whose plasma level was less than 98 micrograms/ml (average 75 micrograms/ml), and group II (seven patients), whose plasma level was greater than 98 micrograms/ml (average 151 micrograms/ml). In both groups, there was a significant drop in the systolic blood pressure after indoramin administration (129 +/- 22 to 111 +/- 23 mm Hg; p less than 0.001). There was a marked improvement in the sinus node recovery time in group I only (271 +/- 94 to 147 +/- 30 ms; p greater than 0.01). Similarly, there was a decrease in the AH interval during fixed-rate atrial pacing (128 +/- 33 to 100 +/- 37 ms; p less than 0.05) and a significant decrease in the Wenckebach cycle length (372 +/- 85 to 347 +/- 74 ms; p less than 0.05) after indoramin in group I only. At the atrial level, there were no significant effects in either group; however, there was a significant increase in the ventricular effective refractory period in group II (231 +/- 35 to 264 +/- 64 ms; p less than 0.05) but not in group I.(ABSTRACT TRUNCATED AT 250 WORDS)

Non-invasive assessment of early cardiac involvement in systemic sclerosis.

Twenty-eight patients with wide spectrum organ involvement of progressive systemic sclerosis but without signs or symptoms suggestive of cardiac involvement were studied by non-invasive cardiac techniques. The 12-lead electrocardiogram showed abnormalities in 6 patients: one had abnormal T waves and 5 had complete or incomplete right bundle branch block. Twenty-four hour ambulatory electrocardiography demonstrated higher average heart rates than in similar aged controls (82 +/- 9 vs 74 +/- 9 beats/min, P less than 0.05). In one patient a short run of ventricular tachycardia was recorded. No other significant arrhythmia was documented. Echocardiographic measurements were within normal ranges but small pericardial effusions were observed in two patients (7%). Resting first pass radionuclide angiography, utilizing 12 mCi of technetium 99m were performed in 23 patients. Seven patients (30%) had abnormal wall motion (diffuse hypokinesia), with a significant decrease in ejection fraction in comparison to those with normal wall motion (44 +/- 6% vs 60 +/- 6% P less than 0.01). Those with abnormal wall motion had suffered the disease longer than those with normal wall motion (13 +/- 4 vs 9.5 +/- 7 y). In conclusion, the heart is involved in half of the patients in this series; non-invasive cardiac assessment is useful in disclosing the early cardiac involvement and may influence long-term management.

Ventricular arrhythmias complicating weight reduction therapy in a patient with a prolonged QT interval.

Serious ventricular arrhythmias are known to occur in patients with long QT intervals. We describe a case of torsade de pointes occurring in a patient with a prolonged QT interval while taking a 1000 calorie diet, diethylpropion hydrochloride (Tenuate Dospan) and bendrofluazide. In patients with long QT intervals, hypokalaemia and drugs which further delay repolarization may facilitate the development of life threatening arrhythmias.

Five-year follow-up of 101 elderly subjects by means of long-term ambulatory cardiac monitoring.

Long-term follow-up of 101 healthy elderly subjects living independently in the community has been undertaken by means of clinical examination, resting ECG and 24-hour ambulatory cardiac monitoring. It appears that the finding of ventricular premature complexes at the rate of 10 per hour or greater is associated with a significant increase in mortality. The prevalence of atrial fibrillation, initially found to be 11%, rises with age to 17% by the age of 84 years. Long-term ambulatory monitoring is essential in the proper documentation of paroxysmal atrial fibrillation. Bundle branch block also occurs in over 10% of elderly people and the prevalence rises steeply with age, so that at the end of this study more than one quarter of the survivors had evidence of His-Purkinje disease. Over 5% of our subjects had definite indications for pacing during the period of follow-up and lends support to the opinion that the current pacemaker implantation rate in the United Kingdom is below the optimal level.