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Biomedical subjects

A W Nathan

Publications and source records attributed to A W Nathan.

At least 37 records · Page 2Linked to original sources
PubMed1991

Recognition of multiple tachyarrhythmias by rate-independent means using a small microcomputer.

New implantable devices are now available that can offer different therapies for different arrhythmias but they need a method of discriminating between these rhythms. Heart rate analysis is predominantly used to discern between sinus rhythm (SR) and pathological tachycardias but this may be of limited value when the rates of the rhythms are similar. An enhanced form of Gradient Pattern Detection (GPD) has been developed using an 8-bit microcomputer that can distinguish between SR and up to three other arrhythmias in real time. This is a method based on electrogram morphology where each rhythm's specific electrogram is classified by a sequence of gradient 'zones'. The microprocessor of the computer is of similar processing power to ones used in current pacemakers. Five patients with multiple arrhythmias were studied. Four had ventricular tachycardia (VT) and one had three conduction patterns during supraventricular tachycardia (SVT). Bipolar endocardial right ventricular electrograms were recorded during SR and tachycardia in all patients. The computer would first 'learn' about each different rhythm by a semi-automatic means. Once all the rhythms were learned the program would enter the GPD analysis phase. The computer would output a series of real-time rhythm specific marker codes onto a chart recorder as it recognized each rhythm. Sixteen different arrhythmias (13 VT, 3 SVT) were examined for this study. All rhythms (including SR) were distinguished from each other except in the case of one patient with six VTs where two VTs had identical shapes and therefore could not be detected apart. The method would be a useful addition to heart rate analysis for future generations of microprocessor assisted pacemakers.

Algorithms↗
PubMed1990

Extensive endocardial resection for recurrent ventricular tachyarrhythmias.

Twenty-two consecutive patients underwent elective map-guided extensive endocardial resection (EER) for recurrent ventricular tachyarrhythmias (VT) of whom 20 were male. The ages ranged from 43 to 74 years (mean 57). All arrhythmias were ischaemic in origin. The mean ejection fraction was 29%. The presenting arrhythmias were ventricular tachycardia in 14, ventricular fibrillation (VF) alone in 1 and ventricular tachycardia and VF in 7. Useful additional intraoperative mapping was obtained in 19 patients. Under cardioplegic arrest, the scarred left (22) and where indicated right (4) ventricular endocardium was extensively resected. Resection of scarred papillary muscles was avoided and where indicated, localised cryoablation was performed: 21/22 had concomitant aneurysmectomy and/or coronary artery bypass grafting. There was 1 (4.5%) operative death. All survivors (95.5%) underwent postoperative electrophysiological studies at around 1 week. None had inducible arrhythmias. There were 3 (13.5%) late cardiac deaths, all due to primary cardiac failure without recurrence of arrhythmia. Of 17 (77%) long-term survivors, 16 (94%) are VT-free on no anti-arrhythmic medication at a mean follow-up of 37.2 months. One developed a new arrhythmia at 1 year which is controlled on medication. EER offers a high rate of success in ablating VT in association with a low operative mortality and good prospect of VT-free long-term survival.

Adult↗
PubMed1990

An acute study of the electrophysiological and haemodynamic effects of intravenous UK-52,046, a novel alpha 1-adrenoceptor antagonist.

The acute electrophysiological and haemodynamic effects of UK-52,046, a novel alpha 1-adrenoceptor antagonist (0.5 microgram kg-1) were studied in 10 patients. Resting and paced conduction intervals, refractory periods, Wenckebach cycle length and sinus node recovery time were measured and compared with baseline values. Haemodynamic measurements including cardiac output were measured before and after drug administration. Changes in QRS interval (83 to 105 ms) and QRS duration during sinus rhythm (83 to 105 ms) or during constant atrial pacing (85 to 109 ms), were not significant (P greater than 0.05). Myocardial refractoriness and sinus node recovery time were not altered by the drug. Slight increases in mean heart rate (72.5 to 78.8 beats min-1), mean right atrial pressure (4.5 to 5.5 mm Hg) and mean cardiac output (5.4 l min-1 to 5.7 l min-1), were not significant (P greater than 0.05). Systolic and diastolic arterial pressure, cardiac work indices, and vascular resistance remained unchanged. These results demonstrate the safety of this drug given intravenously in a non-ischaemic setting, and warrant its further investigation as an antiarrhythmic agent in myocardial ischaemia.

Adrenergic alpha-Antagonists↗
PubMed1990

A study of the use of flecainide acetate in the long-term management of cardiac arrhythmias.

One hundred and sixty-nine patients with a wide range of cardiac arrhythmias and who had been treated with chronic oral flecainide acetate were reviewed retrospectively. The most common arrhythmia was atrial fibrillation (32%), and 20% of the patient population had the Wolff-Parkinson-White syndrome. Five hundred and three treatment episodes were assessed, 254 with flecainide alone or in combination, mean duration 7.3 +/- 9.4 months, and 249 without flecainide, mean duration 9.5 +/- 12.3 months. The most common dose for flecainide was 200 mg/day (57% of episodes), and it was used alone in 82% of flecainide treatment episodes. Arrhythmia frequency was reduced or abolished in 73% of flecainide treatment episodes, with little difference between arrhythmia groups. Unwanted effects were seen in 14% of flecainide treatment episodes, and half of these cases were managed by dose adjustment. It is concluded that flecainide acetate is effective in a wide range of cardiac arrhythmias, and that long-term management problems are few.

Administration, Oral↗
PubMed1988

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.

Adolescent↗
PubMed1987

Intravenous flecainide acetate for the clinical management of paroxysmal tachycardias.

Intravenous flecainide acetate (2 mg/kg) was administered to 40 patients undergoing routine electrophysiological evaluation for the investigation of recurrent paroxysmal tachycardias. Ten patients had recurrent atrial flutter, 11 patients had recurrent atrial fibrillation, one of whom also had paroxysmal left atrial tachycardia, and 19 patients had recurrent ventricular tachyarrhythmias (17 with recurrent ventricular tachycardia and 2 with recurrent fascicular tachycardia). Flecainide was administered during tachycardia (over 5 to 10 minutes) to all patients with atrial flutter, to 10 patients with atrial fibrillation, and to 17 patients with ventricular tachyarrhythmias. In the remaining 3 patients with ill-sustained arrhythmias flecainide was administered during sinus rhythm and reinitiation of tachycardia was then attempted. Flecainide restored sinus rhythm in only 2 patients with atrial flutter (20%), in 9 patients with atrial fibrillation (90%), in 12 patients with ventricular tachycardia (80%), and in one of the 2 patients with fasicular tachycardia. Flecainide also successfully terminated the left atrial tachycardia. Two patients experienced proarrhythmic side effects during flecainide administration, one of whom required intervention by cardioversion. Minor dose effects included oral paresthesia, transient drowsiness or dizziness, and occasional visual blurring. Flecainide acetate is an effective antiarrhythmic agent for the acute termination of recent onset paroxysmal atrial and ventricular tachyarrhythmias.

Adolescent↗
PubMed1987

The proarrhythmic effects of antiarrhythmic drugs.

Although antiarrhythmic drugs are effective for controlling cardiac arrhythmias, they may also induce or exacerbate them. Case reports have appeared implicating all classes of antiarrhythmic drugs. It is difficult to assess the size of the problem in practice, as it varies with different subgroups of patients, but rates of up to 13% have been found where proarrhythmic effects were actively sought. Their occurrence is affected both by the electrophysiologic characteristics of the drugs and by the arrhythmia substrate. Mechanisms of proarrhythmic effects may be classified according to the electrophysiologic and hemodynamic effects of the drugs. Detection of drug-induced arrhythmias depends on appreciation of the problem by physicians and, although there are few clear predictors, some form of monitoring of antiarrhythmic drug treatment is recommended. Management of such arrhythmias when they occur involves withdrawal of the offending agent, correcting contributory factors, and reassessing the initial arrhythmia and the strategy for its management.

Anti-Arrhythmia Agents↗
PubMed1987

A comparison of once daily bisoprolol, 5 and 10 mg, and atenolol 100 mg in the treatment of angina pectoris.

The efficacy and safety of the new cardioselective beta-blocker bisoprolol 5 mg and 10 mg once daily in the treatment of angina pectoris was compared with atenolol 100 mg once daily. 19 patients with coronary artery disease and angina of effort completed a randomised, three-way crossover study which consisted of six-week treatment periods preceeded by a two-week placebo washout. Treadmill exercise stress tests were carried out approximately 24 hours after each dose, at the end of the placebo period and after 2 and 6 weeks of each active treatment period. Patients recorded their angina attack rate and GTN consumption on diary cards. Number of anginal attacks, GTN consumption, resting and exercise systolic blood pressure, heart rate and double product were reduced, and both exercise duration and time to 1 mm ST-segment depression during exercise were increased to a similar extent by all three treatment regimens (P less than 0.01, paired t test). The only differences between the treatments were that the reductions in heart rate, double product and exercise blood pressure tended to be smaller after 6 weeks of bisoprolol 5 mg. Generally, there was no significant difference between the improvements measured at week 2 of each phase and at week 6 (P greater than 0.05, analysis of variance). All three dosage regimens were well tolerated. The data indicate that there is no difference between the safety and efficacy of bisoprolol 10 mg and atenolol 100 mg once daily in the treatment of angina pectoris. In addition, the 10 mg dose of bisoprolol would seem to have only a small advantage over the lower 5 mg once daily dose.

Aged↗
PubMed1986

Acute and chronic effects of sotalol and propranolol on ventricular repolarization using constant-rate pacing.

Sotalol and propranolol were administered both intravenously and orally in conventional equipotent beta-blocking doses to 8 patients with permanent programmable ventricular pacemakers to study their effects on ventricular repolarization. Sotalol prolonged the QT interval by 6.5% (430 to 455 ms) after intravenous administration (p less than 0.01) and by up to 11.5% (430 to 483 ms) after 4 weeks of oral treatment (p less than 0.001). This was entirely due to prolongation of the JT interval, since there was no effect on QRS duration. The magnitude of QT and JT prolongation related to the serum level but the correlation was not statistically significant. QT prolongation was exaggerated after chronic treatment despite lower serum levels of sotalol (2.0 micrograms/ml) compared with levels after acute administration (3.5 micrograms/ml). After propranolol was given, there was no consistent change in QT or JT intervals, and although there was a tendency to slight prolongation of QT interval, by 2.5% after chronic oral administration, this was not statistically significant. This suggests that the prolongation of ventricular repolarization by sotalol is not caused by beta-blockade, but by its class III activity, and that chronic treatment increases the effect. There was no significant effect on chronic ventricular pacing threshold after intravenous or oral administration of either drug.

Adult↗
PubMed1986

Detection of pathological tachycardia by analysis of electrogram morphology.

Pacemaker recognition of pathological tachycardia relies on heart rate analysis. This can lead to misdiagnosis when sinus tachycardia exceeds the preset tachycardia response trigger rate. We have explored a method for automatic tachycardia diagnosis by analysis of bipolar endocardial electrogram morphology. Electrograms were recorded from 11 patients (pts) during sinus rhythm and during a total of 20 abnormal rhythms: retrograde atrial depolarization from ventricular pacing in six patients; atrioventricular reentry tachycardia in five patients with intermittent left bundle branch block in one of those; AV nodal reentry tachycardia in five patients and ventricular tachycardia in three patients. Posture and respiration were varied during all rhythms except ventricular tachycardia. The electrograms were then digitized and converted to a form in which the amplitudes were proportional to the rates of change of the original electrogram (equivalent to a first time derivative); the derived signal was then analyzed by a new gradient pattern detection (GPD) program. Analysis of the processed atrial signals by GPD resulted in automatic recognition of abnormal rhythms from sinus rhythm in all cases except for one patient's retrograde atrial depolarization. At the ventricular level, GPD successfully distinguished all abnormal rhythms from sinus rhythm including recognition of left bundle branch block and varying degrees of preexcitation. Respiratory and postural variation did not affect the recognition process. We conclude that electrogram GPD has successfully and automatically detected a variety of arrhythmias which can be treated by implantable pulse generators and may, therefore, be a useful adjunct to heart rate analysis in future generations of such antitachycardia pacemakers.

Adolescent↗
PubMed1986

Unusual sinus node response curves in two cardiac transplant recipients.

We describe unusual responses of the sinus node to programmed atrial stimulation in two asymptomatic cardiac transplant recipients. In one patient the sinoatrial conduction time, calculated using the revised method of Strauss, is extremely short (5 ms), and in the other it is extremely long (460 ms). The various mechanisms that might be involved in these atypical responses to atrial extrastimulation are discussed. These include sinus node suppression, shift of pacemaker, direct stimulation of the sinus node and shortening of the sinus node action potential duration.

Action Potentials↗
PubMed1986

Clinical experience with a software based tachycardia reversion pacemaker.

Current generation antitachycardia pacemakers suffer from limitations concerning detection and distinction of pathological tachycardia and also from the termination modes available. To overcome many of these limitations, a new device (Intermedics Intertach 262-12) has been developed, and has now been implanted in nine patients, all of whom had failed drug treatment. Since implantation, all patients have complete control of their arrhythmias, and only one now requires drug therapy.

Adult↗
PubMed1985

Cardiac pacing in an elderly population with a satellite clinic in a district general hospital.

It has been suggested that in the United Kingdom the rate of implantation of cardiac pacemakers is too low. One possible reason for this may be the inadequate availability or usage of ambulatory ECG monitoring services for elderly patients. Since the introduction of such a service in Crawley, West Sussex, pacemaker implantation has increased from less than five to more than 20 per annum. Ninety-five of the 102 pacemakers (93%) implanted in that time were in patients over the age of 65 years and 68 of them were over 70 years. This rate of implantation is equivalent over the nation as a whole to at least 8000 new pacemakers per year. This represents a 14-23% increase over the present implantation rate. Since all patients were symptomatically improved and survived on average more than 30 months, despite their advanced ages, pacemaker implantation was certainly justified. The establishment of a local pacemaker surveillance service reduced the need for elderly patients to travel long distances for pacemaker checks.

Aged↗
PubMed1985

Successful treatment of atrial tachycardias with flecainide acetate.

Intravenous flecainide successfully terminated atrial tachycardia in three patients. Maintenance treatment with oral flecainide prevented the recurrence of tachycardia for up to three years. These results suggest an additional use for flecainide which should be further explored.

Adult↗
PubMed1985

Clinical usefulness of flecainide acetate in the treatment of paroxysmal supraventricular arrhythmias.

Flecainide acetate depresses both the upstroke of the intracellular action potential and the rate of diastolic depolarisation in isolated tissue preparations of atrial myocardium. It produces no consistent effect on action potential duration. Predictably, in the human heart, studied by clinical cardiac electrophysiological techniques, conduction velocity through atrial myocardium, the atrioventricular (AV) node and anomalous tissue is depressed following flecainide administration. Refractoriness of normal atrial or AV nodal myocardium is not prolonged but the recovery time of anomalous or abnormal tissue is lengthened by the drug. In response to the intravenous injection of flecainide, atrial fibrillation (90%), atrial tachycardia (100%), intra-AV nodal tachycardia (89%) and atrioventricular re-entrant tachycardia (80%) are generally terminated, and although atrial flutter is slowed, only a small proportion (20%) is terminated. There is little experience of the long term treatment of supraventricular tachycardia with oral flecainide. However, preliminary results suggest that flecainide is equally effective in the treatment of both supraventricular and ventricular arrhythmias. Thus, flecainide acetate is a 'broad spectrum' antiarrhythmic agent.

Animals↗
PubMed1985

The proarrhythmic effects of flecainide.

Flecainide acetate, a new potent class I antiarrhythmic agent, was administered to 152 patients (orally to 46, intravenously to 106) over a period of 22 months. Seven patients developed proarrhythmic effects. The only conduction abnormalities induced were PR interval prolongation and QRS complex widening, and no patient developed significant sinus bradyarrhythmias; patients with known serious abnormalities of impulse generation or conduction were excluded from this study. Five patients, of whom only 3 had pre-existing ventricular arrhythmias, developed ventricular tachycardia or ventricular fibrillation. QT and QTc interval prolongation was observed, but was due to QRS complex widening rather than an increase in the JT interval. A patient with Wolff-Parkinson-White syndrome had an inducible orthodromic atrioventricular tachycardia before flecainide administration, but only an antidromic tachycardia was induced after taking the drug. In 1 patient, flecainide administration resulted in an increase of atrial flutter cycle length, which resulted in the development of 1:1 atrioventricular conduction rate, and, overall, a faster ventricular rate. Two patients who developed ventricular arrhythmias were taking other antiarrhythmic agents, and in this series proarrhythmic effects occurred with both normal and high flecainide concentrations. Other published series are also summarised.

Adult↗
PubMed1984

Catheter ablation of atrioventricular conduction.

35 patients with refractory supraventricular arrhythmias were treated in three centres by high-energy shocks delivered to the atrioventricular conduction system from a conventional transvenous pacing catheter. After a mean interval of ten months, 26 patients (74%) had persistent complete heart block, 2 (6%) had intermittent complete heart block, and 3(9%) had first-degree heart block. 3 patients continued to have conducted atrial fibrillation, but with slower ventricular rates than previously, and 1 had normalisation of dual atrio-His conduction. In 1 patient a septal accessory pathway was ablated. 30 patients (86%) are completely symptom-free without additional therapy. There were no important long-term complications. Transvenous ablation of atrioventricular conduction is a safe and effective technique for treating a wide range of refractory atrial and junctional arrhythmias.

Adolescent↗