Kevin J. Hellestrand

Implantable automatic scanning pacemaker for termination of supraventricular tachycardia

Thirteen patients suffering from reentrant supraventricular tachycardia have undergone implantation of a scanning extrastimulus pacemaker. This pacemaker is fully implanted and automatic, and it requires no external control device to activate or control it. The pacemaker is activated when tachycardia occurs. After four cycles an extrastimulus is induced with a preset coupling time from a sensed intracardiac potential, and every four cycles thereafter a further extrastimulus occurs, but on each occasion there is a decrement in coupling cycle by 6 ms until 90 ms of the cardiac cycle has been scanned by extrastimuli. When necessary, two extrastimuli can be introduced with a fixed but preset coupling time between them. Every four beats two extrastimuli are induced but the coupling time between the spontaneous cardiac potential and the first stimulus is decreased by 6 ms until 90 ms of the cardiac cycle has been scanned. The coupling time between the two stimuli is fixed throughout the scan. When termination of tachycardia occurs the successful timing variables are retained in the pacemaker memory so that at the onset of the next episode of tachycardia these settings are used first. Pacemaker pulse width, sensitivity, tachycardia trigger rate, coupling intervals for both stimuli and the use of single or double extrastimuli are all programmable transcutaneously. Three patients required single, and seven patients double ventricular premature stimuli; three patients required double atrial premature stimuli for termination of tachycardia. Despite frequent attacks of tachycardia before implantation, only two patients had a sustained attack of tachycardia after pacemaker implantation.

Effect of the Antiarrhythmic Agent Flecainide Acetate on Acute and Chronic Pacing Thresholds

To determine the effect of flecainide acetate, a Class IG antiarrnythmic drug, the medication was given to 28 patients with ventricular pacing electrodes. Eleven patients with temporary pacing electrodes (Group I) received intravenous flecainide (2 mg/kg over 10 minutes). Ten patients with chronic permanent electrodes (Group II) were given the same dose at the time of elective pulse generator change. Seven, with implanted multiprogrammable pacemakers capable of threshold analysis (Group III), were given intravenous flecainide and 5 of these were then given the drug orally for up to 3 weeks (100 mg/day increasing to 400 mg/day). In Group I the threshold measured at a pulse width of 0.5 ms rose from a control value of 0.66 to 1.44 volts after 10 minutes (p < 0.01). In Group II the threshold rose from 1.73 to 2.13 volts (p < 0.01) and 2 patients had total suppression of their ventricular escape rhythm for approximately one hour. In Group III patients, intravenous flecainide resulted in a rise of the pulse width threshold measured at 2.7 volts from 0.14 to 0.22 ms (p<0.02) and at 4.9 volts from 0.06 to 0.11 ms (p<0.05) after 10 minutes. After 3 weeks of oral therapy the threshold at 2.7 volts had risen from 0.09 to 0.28 ms (p < 0.02) and al 4.9 volts from 0.06 to 0.16 ms (p< 0.05). Flecainide significantly increased both acute and chronic thresholds and the most marked rise (> 200%) occurred during chronic oral therapy. Both intravenous and oral flecainide should be used with care in patients with either temporary or permanent pacing systems.

Proarrhythmic effects of the new antiarrhythmic agent flecainide acetate

Flecainide acetate, a new potent class I antiarrhythmic agent, was given to 152 patients (46 orally and 106 intravenously) 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 developed ventricular tachycardia or ventricular fibrillation of whom only three had preexisting ventricular arrhythmias. QT and QTc interval prolongation was observed but was due to QRS complex widening rather than to an increase in the JT interval. A patient with the Wolff-Parkinson-White syndrome had an inducible orthodromic atrioventricular (AV) tachycardia prior to flecainide, but only an antidromic tachycardia was induced after the drug. In one patient flecainide administration resulted in an increase of atrial flutter cycle length which resulted in development of 1:1 AV conduction and overall 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.

Sinoatrial function after cardiac transplantation

The function of both the denervated donor and innervated recipient sinus nodes of 14 asymptomatic cardiac transplant recipients was assessed. Tests of sinoatrial function were performed in 14 donor and 10 recipient atria. The mean spontaneous cycle length of the recipient atria was significantly longer than that of the donor atria (944 +/- 246 versus 663 +/- 158 ms, p less than 0.01). Donor sinus node recovery time was prolonged in four patients (greater than 2,500 ms in two) and recipient recovery time was prolonged in six patients. In those patients with normal sinus node function tests, the recovery time of the recipient sinus node was longer than that of the donor sinus node (1,170 +/- 207 versus 864 +/- 175 ms, p less than 0.02). The pattern of response of recovery times to increasing pacing rate was predictable and organized in the donor but chaotic in the recipient, and the longest sinus node recovery time occurred at the shortest pacing cycle length used in 12 of the 14 donor atria but in only 1 of the 10 recipient atria (p less than 0.001). Secondary pauses occurred in none of the normal donor atria and in all of the abnormal donor atria (p less than 0.001); however, they occurred in both normal and abnormal recipient atria. The recipient and donor atria were paced alone and synchronously in the same patients. Synchronous pacing had no effect on the recovery times of the donor sinus node but significantly lengthened those of the recipient (sinus node recovery time: 1,266 +/- 218 to 1,547 +/- 332 ms, p less than 0.02; corrected recovery time: 322 +/- 102 to 686 +/- 188 ms, p less than 0.01). In the donor atria, abnormal recovery time was invariably associated with abnormal sinoatrial conduction time. There was a strong correlation between sinoatrial conduction time measured by the methods of Strauss and Narula and their coworkers in the donor atria (r = 0.98, p less than 0.001) but not in the recipient atria (r = 0.72). In the absence of autonomic influences, tests of sinus node function of the donor atria produce predictable and consistent results and, therefore, may be more clinically reliable than in intact human subjects. There is a high incidence of recipient sinus node dysfunction in asymptomatic long-term survivors of cardiac transplantation.

The Proarrhythmic Effects of Flecainide

SummaryFlecainide 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 anti-arrhythmic agents, and in this series proarrhythmic effects occurred with both normal and high flecainide concentrations. Other published series are also summarised.RésuméL’acétate de flecainide, nouvel et efficace antiarythmiqe de la classe I a été administré à 152 malades (46 par voie orale, 106 par voie intraveineuse) pendant 22 mois. Sept malades ont montré des effets arythmogènes. Les seules anomalies de la conduction ont consisté en un allongement de PR et un élargissement de QRS. A ucun malade n ’a, en fait, développé de bradyarythmie sinusale. Les sujets porteurs d’anomalies sérieuses de l’activité pacemaker ou de la conduction avaient cependant été exclus de l’essai. Cinq sujets dont 3 souffraient d’arythmies ventriculaires ont développé soit une tachycardie soit une fibrillation ventriculaires. Les intervalles QT et QTc ont été allongés, conséquence plutôt de l’élargissement de QRS que d’un allongement de JT. Chez un sujet porteur d’un syndrome de Wolff-Parkinson-White et chez lequel on pouvait induire une tachycardie atrioventriculaire orthodromique avant administration de flecainide, on n’a pu provoquer qu ’une tachycardie antidromique après administration de flecainide. Chez un malade, le flecainide a augmenté la durée du cycle d’ur. flutter auriculaire aboutissant à un rythme 11 et à un rythme ventriculaire plus rapide. Deux malades qui ont développé une arythmie ventriculaire prenaient d’autres antiarythmiqes et dans cette série, les effets arythmogènes sont survenus que les concentrations de flécainide soient normales ou élevées. D’autres études publiées sont également rappelées.ZusammenfassungDas neue potente Klasse I-Antiarrhythmikum Flecainidacetat wurde 152 Patienten (46 oral, 106 intravenös) über einen Zeitraum von 22 Monaten verabreicht. Bei 7 Patienten trat ein proarrhythmischer Effekt auf. Die einzigen induzierten Leitungsabnormitäten bestanden in einer Verlängerung des PR-Intervalls und Ausweitung des QRS-Komplexes. Kein Patient entwickelte eine signifikante Sinusbradyarrhythmie. Patienten mit bekannten schweren Anomalien der Reizbildung und Reizleitung waren von dieser Studie ausgeschlossen. Bei 5 Patienten, von denen bei nur3 bereits vorher ventrikuläre Arrhythmien bestanden, traten ventrikuläre Tachykardien oder Kammerflimmern auf. Die beobachtete Verlängerung des QT-und QTc-Intervalls war eher auf eine Erweiterung des QRS-Komplexes als auf einen Anstieg des JT-Intervalls zurückzuführen. Ein Patient mit Wolff-Parkinson-White-Syndrom hatte vor der Gabe von Flecainid eine induzierbare orthodrome atrioventrikuläre Tachykardie. Nach Einnahme des Medikaments wurde jedoch nur eine antidrome Tachykardie induziert. Bei einem Patienten ergab die Verabreichung von Flecainid eine erhöhte Cycluslänge des Vorhofβatterns, was zur Entwicklung einer atrioventrikulären Leitungsrate von 1:1 und insgesamt einer schnelleren Ventrikelrate führte. Zwei Patienten, die ventrikuläre Arrhythmien entwickelten, nahmen andere Antiarrhythmika. Hierbei tratenproarrhythmische Effekte sowohl mit normalen als auch hohen Flecainidkonzentrationen auf. Andere publizierte Untersuchungen werden zusammengefaβt.

The use of active fixation electrodes for permanent endocardial pacing via a persistent left superior vena cava.

Two patients underwent permanent endocardial pacing for complete atrioventricular block. In each case a persistent left superior vena cava was either suspected or known to be present. An active fixation electrode was passed down the left superior vena cava and the tip positioned in the apex of the right ventricle. Stable ventricular pacing was achieved for the follow‐up period of approximately six months. With the availability of such active fixation electrodes the presence of a persistent left superior vena cava no longer mandates insertion of an endocardial electrode via the right superior vena cava. when present, or implantation of an epicardial pacing system. (PACE, Vol. 5, March‐April, 1982)

Clinical Usefulness of Flecainide Acetate in the Treatment of Paroxysmal Supraventricular Arrhythmias

SummaryFlecainide 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-A V 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.RésuméL’acétate de flécainide est dépresseur de la conduction du potentiel d’action intracellulaire et de la fréquence de dépolarisation diastolique sur des préparations tissulaires isolées de l’oreillette. Il n ’a pas, in vitro, d’effet notable sur la durée du potentiel d’action. Les études électrophysiologiques en clinique montrent, comme on, pouvait donc s’y attendre, un effet dépresseur du flécainide sur la vitesse de conduction à travers l’oreillette, le noeud auriculoventricutaire et dans le cas de certains syndromes cardiaques avec anomalies tissulaires. La période réfractaire du myocarde auriculaire et du noeud auriculoventriculaire normal n ’est pas allongée alors que la phase de potentiel de repos l’est en cas d’anomalie myocardique. L’injection intraveineuse de flecainide arrête la fibrillation auriculaire (90%), la tachycardie auriculaire (100%), la tachycardie par réentrée intranodale auriculoventriculaire (89%) et la tachycardie auriculoventriculaire par réentrée (80%) tandis que, si le flutter auriculaire est toujours ralenti, il n’est arrêté que dans 20% des cas. On sait peu de choses sur les résultats du traitement à long terme des tachycardies supraventriculaires par le flecainide administré par voie orale. Des données préliminaires suggèrent que le flecainide a la même efficacité sur les arythmies ventriculaires et supraventriculaires. Il serait ainsi un antiarythmique à “large spectre”.ZusammenfassungFlecainidacetat vermindert sowohl die Anstiegssteilheit des intrazellulären Aktionspotentials als auch die Geschwindigkeit der diastolischen Depolarisation in isolierten Präparationen des Atrium; es hat jedoch keinen konsequenten Effekt auf die Dauer des Aktionspotentials. Wie voraussagbar, ist nach Applikation von Flecainid beim mit klinisch kardialen elektrophysiologischen Techniken untersuchten menschlichen Herzen die intra-atriale Leitungszeit sowie die Leitungszeit durch den atrioventrikulären (A V-) Knoten und durch anomales Gewebe herabgesetzt. Die Refraktäritatät von normalem atrialen oder AV-Knoten-Myokard wird durch das Pharmakon nicht verlängert, aber die Erholungszeit von anomalem oder abnormalem Gewebe verlängert. Als Reaktion auf die intravenöse Injektion von Flecainid werden im allgemeinen Vorhofflimmern (90%), Vorhoftachykardien (100%), intra-A V-Knotentachykardien (89%) und AV-Re-entry-Tachykardien (80%) terminiert. Obgleich sich das Vorhofflimmern verlangsamt, wird nur ein kleiner Teil (20%) beendet. Über die Langzeittherapie mit oralem Flecainid bei der supraventrikulären Tachykardie liegen nur wenig Erfahrungen vor. Erste Ergebnisse lassen jedoch vermuten, daβ Flecainid sowohl bei der Behandlung von supraventrikulären als auch ventrikulären Arrhythmien gleich wirksam ist. Flecainidacetat stellt somit ein “Breit-band”-Antiarrhythmikum dar.

The electrophysiologic characteristics of the transplanted human heart

The electrophysiologic characteristics of the denervated human heart were assessed in 14 cardiac transplant recipients. Conduction intervals and refractory periods were measured at pacing cycle lengths of 500 msec and 400 msec. The faster pacing rate caused lengthening of the AH interval (83 +/- 23 msec to 116 +/- 41 msec, p less than 0.01) and shortening of the QT (338 +/- 27 msec to 313 +/- 22 msec, p less than 0.001) and JT (249 +/- 21 msec to 229 +/- 19 msec, p less than 0.001) intervals. There was no change in the SA, HV, or QRS durations. Wenckebach periodicity occurred at a longer cycle length in the retrograde than in the anterograde direction (409 +/- 96 msec vs 318 +/- 46 msec, p less than 0.01) and anterograde conduction was better than retrograde conduction in 13 of the 14 patients (93%). Increasing pacing cycle length resulted in shortening of the atrial effective (203 +/- 28 msec to 190 +/- 25 msec, p less than 0.001), ventricular effective (224 +/- 18 msec to 211 +/- 17 msec, p less than 0.01), and AV nodal functional (367 +/- 38 msec to 357 +/- 36 msec, NS) refractory periods. The AV nodal effective refractory period lengthened (294 +/- 31 msec to 314 +/- 52 msec, p less than 0.05). There was a close correlation between AV Wenckebach cycle length and the functional refractory period of the AV node (r = 0.853, p less than 0.001). These results are qualitatively and quantitatively similar to those reported in the innervated heart. The autonomic nervous system appears to have little influence on the resting electrophysiologic characteristics of the atrioventricular conduction system in the innervated heart.

Clinical Evaluation of an Adaptive Tachycardia Intervention Pacemaker with Automatic Cycle Length Adjustment

An exlernal version of a new pacemaker designed for automatic tachycardia termination is described. In response to a tachycardia, defined as four successive beats occurring at a rate faster than a variable preset value, a number of stimuli (1–15) are generated. The initial coupling interval and subsequent pacing cycle intervals (where applicable) are always the same. Failure to terminate tachycardia results in the reduction of the pacing cycle length by 6 ms before termination of tachycardia is re‐attempted. Pacing cycle length reduction may be repeated up to 16 times. If all coupling intervals of a single extrastimulus fail to achieve tachycardia termination, a second stimulus is scanned with the first through the same range of decrements. Additional stimuli, to a total of 15. could be used. A memory function is incorporated to retain and re‐use a successful sequence. The pacemaker was evaluated in 16 patients with recurrent “supraventricular” (atrioventricular and intra A‐Vnodal) tachycardia, using right ventricular pacing. Termination was successful in all patients. More than two stimuli were necessary in only two patients, one of whom required five, and the other six stimuli. No unwanted arrhythmias were induced. (PACE, Vol. 5, March‐April, 1982)

Unusual atrial potentials in a cardiac transplant recipient. possible synchronization between donor and recipient atria

It is usual to record independent activity from both the innervated recipient and the denervated donor atria in cardiac transplant recipients except for occasional, short-lived periods of entrainment that may occur during exercise. In this report a case is described in which, following orthotopic cardiac transplantation, the recipient and donor atria remained synchronized during a variety of physiological and non-physiological situations. Under no circumstances did the two sets of atria beat independently. The mechanisms that might be involved in this unique situation are discussed.