Ryszard B. Krol

Prevention of recurrent atrial fibrillation with chronic dual-site right atrial pacing.

OBJECTIVES We investigated 1) the feasibility, safety and efficacy of multisite right atrial pacing for prevention of atrial fibrillation (AF); and 2) the ability of atrial pacing in single- and dual-site modes to increase arrhythmia-free intervals in patients with drug-refractory AF. BACKGROUND We recently developed and applied a novel technique of dual-site right atrial pacing in an unselected group of consecutive patients with AF requiring demand pacing. A prospective crossover study design was used to evaluate single- and dual-site right atrial pacing modes. METHODS The frequency of AF during the 3 months before pacemaker implantation was analyzed. Consecutive consenting patients underwent insertion of two atrial leads and one ventricular lead with a DDDR pulse generator. Patients were placed in a dual-site pacing mode for the first 3 months and subsequently mode switched to single site pacing for 3 months. Mode switching was repeated at 6-month intervals thereafter. RESULTS Atrial pacing resulted in a marked decline in AF recurrences (p < 0.001). During dual-site pacing with an optimal drug regimen, there was no AF recurrence in any patient compared with five recurrences in 12 patients during single-site pacing (p = 0.03). The mean (+/-SD) arrhythmia-free interval before pacing (14 +/- 14 days) was prolonged with dual- (89 +/- 7 days, p < 0.0001) and single-site pacing (76 +/- 27 days, p < 0.0001). Symptomatic AF episodes showed a declining trend during dual- and single-site pacing compared with those during the preimplantation period (p = 0.10). Mean antiarrhythmic drug use for all classes declined from 4 +/- 1.9 drugs before implantation to 1.5 +/- 0.5 (p < 0.01) drugs after implantation. Twelve (80%) of 15 patients remained in atrial paced rhythm at 13 +/- 3 months. CONCLUSIONS We conclude that multisite right atrial pacing is feasible, effective and safe for long-term application. Atrial pacing significantly prolongs arrhythmia-free intervals in patients with drug-refractory paroxysmal AF. Dual-site right atrial pacing may offer additional benefits and should be considered either as the primary mode or in patients unresponsive to single-site pacing.

Acute Effects of Dual-Site Right Atrial Pacing in Patients With Spontaneous and Inducible Atrial Flutter and Fibrillation

OBJECTIVES We tested the ability of dual-site right atrial pacing to prevent atrial fibrillation (AF) or atrial flutter induced by single-site atrial pacing and correlated its efficacy with clinical patient characteristics, atrial activation times and refractory periods. BACKGROUND Prevention of recurrent AF with long-term dual-site right atrial pacing has been demonstrated in our previous studies. However, the mechanism of antiarrhythmic benefit is unclear. METHODS Using standard electrophysiologic methods, baseline electrocardiographic and electrophysiologic measurements (mean +/- SD) were obtained. Programmed atrial stimulation was performed for AF or atrial flutter induction. Atrial pacing was performed at two drive cycle lengths (600 and 400 ms) and followed by one to three atrial extrastimuli at one to four pacing sites in the right atrium. In patients with inducible AF or atrial flutter, reinduction was then attempted during a dual-site atrial pacing drive train. This was achieved by simultaneously pacing at the high right atrium and coronary sinus ostium at an identical rate to the baseline stimulation, with the atrial extrastimuli being delivered at the pacing site responsible for the initial AF episode initiation. RESULTS Twenty patients (10 men, 10 women, mean [+/- SD] age 64 +/- 16 years) with symptomatic AF (n = 10) or atrial flutter (n = 10) were studied. There was a significant abbreviation of the P wave duration to 103 +/- 17 ms with dual-site pacing compared with sinus rhythm (120 +/- 12 ms, p = 0.005) and high right atrial pacing (121 +/- 17 ms, p = 0.005). This was also associated with a characteristic change in P wave configuration with an inferior and leftward axis shift. The effective refractory period at the high right atrium remained unchanged with dual-site atrial pacing compared with single-site high right atrial pacing. Sixteen patients had inducible AF or atrial flutter and could be tested after dual-site atrial pacing. The induced atrial tachyarrhythmia was suppressed in nine patients (56%), who had either induced AF (n = 5) or atrial flutter (n = 4). The difference in the effective refractory period between the high right atrium and the coronary sinus ostium pacing sites was significantly greater (33 +/- 12 ms) in patients with suppression of atrial tachyarrhythmia with dual-site atrial pacing compared with patients without suppression (15 +/- 13 ms, p = 0.001). P wave abbreviation did not correlate with arrhythmia suppression. There was no correlation between suppression of inducible AF or atrial flutter and demographic or clinical patient characteristics. CONCLUSIONS Dual-site right atrial pacing from the high right atrium and coronary sinus ostium can suppress inducible AF or atrial flutter elicited after single-site high right atrial pacing in selected patients. Acute suppression is more likely in patients with greater dispersion of right atrial refractoriness between these two sites.

Regional right and left atrial activation patterns during single- and dual-site atrial pacing in patients with atrial fibrillation

We examined the activation of the right atrium and left atrium by pacing from different atrial sites using several single- and dual-site atrial pacing modes in patients with atrial fibrillation or flutter. We also analyzed the effect of these pacing modes on fixed coupled extrastimuli in this population. Patients underwent detailed mapping of regional right atrial (RA) and left atrial (LA) sites. Bipolar pacing was performed individually from the high right atrium, coronary sinus ostium, and the distal coronary sinus, and simultaneously from the high right atrium and coronary sinus ostium (dual-site RA pacing) or high right atrium and distal coronary sinus (biatrial pacing). Extrastimuli were delivered from the high right atrium at fixed coupling intervals of 350 and 250 ms. Twenty patients with atrial fibrillation were studied. P-wave duration during pacing was significantly abbreviated by both dual-site RA and biatrial pacing (p <0.001 vs high RA pacing, respectively) but not by any other single-site atrial pacing method. Both dual-site atrial pacing modes also significantly abbreviated P wave durations for closely coupled high RA premature beats (p <0.001) in contrast to high RA pacing. During the basic pacing drive and for high RA extrastimuli, RA activation at the crista terminalis and atrial septum was comparable in sinus rhythm, high RA pacing, and in both dual-site atrial pacing methods, but was significantly delayed by coronary sinus ostial and distal coronary sinus pacing. In contrast, proximal coronary sinus activation was delayed with high RA pacing compared with all other pacing modes, and high RA extrastimuli encountered reduced conduction delay at this location with dual-site atrial pacing modes. LA activation was advanced superiorly by both single-site coronary sinus pacing methods and both dual-site atrial pacing techniques. Inferior and lateral LA activation was advanced by all pacing modes using a coronary sinus pacing site. However, earlier activation of LA sites occurred for high RA premature beats after both dual-site pacing methods (p <0.05) compared with single-site pacing modes. Incremental conduction delay at different atrial regions for closely coupled high RA extrastimuli ranged from 33% to 120% during high RA pacing and was significantly attenuated at multiple RA and LA sites by dual-site RA and biatrial pacing. Distinct global, as well as regional electrophysiologic effects, may mediate the variable antiarrhythmic effects of different and novel atrial pacing methods.

Increased plasma catecholamine levels in patients with symptomatic mitral valve prolapse

Total plasma catecholamine levels, plasma norepinephrine levels, heart rate, and systolic and diastolic pressures were measured in 15 symptomatic patients with mitral valve prolapse and in 19 normal subjects in supine baseline conditions and in a standing position. In the 15 symptomatic patients, total plasma catecholamine levels and plasma norepinephrine levels were significantly elevated in both positions, and heart rate was lower than in normal subjects in the supine position but returned to normal in the upright position. Thus, symptomatic patients with mitral valve prolapse demonstrate increased resting sympathetic tone. In addition, the associated supine bradycardia suggested that increased vagal tone might also be present at rest. These observations support the hypothesis of a dual autonomic dysfunction in these patients and could account for some of the clinical manifestations of the mitral valve prolapse syndrome.

Clinical efficacy and safety of atrial defibrillation using biphasic shocks and current nonthoracotomy endocardial lead configurations

We undertook a prospective randomized clinical trial evaluating efficacy and safety of internal atrial defibrillation in patients with drug-refractory atrial fibrillation (AF). Consecutive patients with paroxysmal or chronic AF were randomly tested with 3 internal atrial defibrillation lead configurations and biphasic shocks. Patients with implanted cardiac pacemakers were tested with the right atrium (RA) and left pulmonary artery or coronary sinus (CS) configuration. Shocks were initially delivered without anesthesia to assess patient tolerance. The need for backup ventricular defibrillation and pacing support was evaluated. Eighteen patients with (n = 15) or without (n = 3) structural heart disease, mean left ventricular ejection fraction 36 +/- 14%, and mean left atrial diameter 4.5 +/- 0.6 cm were studied. The mean defibrillation threshold in the best randomized lead configuration was 9.9 +/- 7.7 J. Mean defibrillation threshold for the right ventricle (RV) and superior vena cava configuration was 13.3 +/- 5 J, which was significantly lower than the RA and axilla configuration (20.1 +/- 7.4 J, p < 0.04) but not the RV to RA configuration (16.5 +/- 11 J, p > 0.2). The mean defibrillation threshold using the RA-left pulmonary artery/CS configuration was 8.9 +/- 9 J (p > 0.2 vs RV-superior vena cava). There was a bimodal distribution of defibrillation thresholds. Low atrial defibrillation thresholds correlated with absence of heart disease, higher ejection fraction, and smaller left ventricular end-diastolic diameter. Shocks were hemodynamically well tolerated, but 2 of 18 patients (11%) had nonsustained ventricular tachycardia after shock delivery. Six of 18 patients (33%) had postshock bradyarrhythmias. Fourteen of 16 patients perceived shocks > or = 3 J as intolerable.(ABSTRACT TRUNCATED AT 250 WORDS) [corrected]

QT interval prolongation and increased plasma catecholamine levels in patients with mitral valve prolapse.

The heart rate corrected QT interval (QTc) and plasma catecholamine (CA) and norepinephrine (NE) levels were measured in 15 symptomatic patients with idiopathic mitral valve prolapse (MVP) and in 19 control subjects. MVP patients showed longer mean QTc and were divided into two groups: group A normal QTc (greater than 440 msec) and group B prolonged QTc (less than 440 msec). In supine resting conditions CA levels were as follows: group A 0.420 +/- 0.035 ng/ml and group B 0.619 +/- 0.104 ng/ml (p less than 0.05); both were greater than control values (0.348 +/- 0.017 ng/ml, p less than 0.005). NE levels were as follows: group A 0.350 +/- 0.031 ng/ml and group B 0.376 +/- 0.052 ng/ml (NS); both were greater than control values (0.242 +/- 0.025 ng/ml, (p less than 0.05). When a standing position was assumed, CA and NE levels increased significantly in all groups but this was most marked in group B as compared to control levels (CA: 1.039 +/- 0.123 ng/ml versus 0.625 +/- 0.037 ng/ml; NE: 0.737 +/- 0.076 ng/ml versus 0.504 +/- 0.031 ng/ml) (p less than 0.001 and p less than 0.05, respectively). Thus the longest QTc was observed in patients with MVP who had the highest levels of CA and NE, in both supine and standing positions. These data may account, in part, for the occurrence of severe ventricular arrhythmias in some patients with MVP and may offer a rationale for adrenergic blockade in that subset of patients with MVP and markedly prolonged QTc.

INTERACTION BETWEEN ELECTRONIC ARTICLE SURVEILLANCE SYSTEMS AND IMPLANTABLE DEFIBRILLATORS : INSIGHTS FROM A FOURTH GENERATION ICD

We present a case report of an inappropriate discharge from a fourth generation implantable cardioverter defibrillator (ICD) as a result of exposure to electromagnetic interference. A 60‐year‐old man implanted with a Medtronic 7219D defibrillator experienced shocks without preceding symptoms while walking through an electronic surveillance system in a store. Though this has been reported, the mechanism of the interaction remains unexplained. The electrogram storage capabilities of this particular device enabled us to establish that this resulted from inappropriate sensing of the electromagnetic interference.

Experience with a third-generation implantable cardioverter-defibrillator

A Medtronic 7216A pacemaker cardioverter-defibrillator was implanted in 16 patients (mean age 56 years) with sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and organic heart disease with a mean left ventricular ejection fraction of 33%. Endocardial and epicardial defibrillation shock efficacy was evaluated before or at implant using 1 to 3 shock patterns, i.e., monophasic single, sequential or simultaneous shocks with dual and triple electrode configurations. Endocardial leads used a common right ventricular cathode and dual anodes, whereas epicardial leads used 2 or 3 helical coil patches. VT termination was evaluated using pacing or shock therapy, or both, whereas only shocks were used in VF. Programmable bradycardia pacing, individual zones for VT and VF detection and individualized pacing and shock therapy for VT and VF were used. Monophasic shocks had epicardial defibrillation thresholds ranging from 3 to 18 (mean 10) J and were comparable for sequential and simultaneous shocks (p greater than 0.2). VT detection rates ranged from 340 to 470 ms and VF detection rates from 270 to 330 ms. VT or VF induction, or both, was performed noninvasively in 13 patients after implant and was reproducibly terminated by rapid pacing alone (5 patients), low-energy shocks (2 patients), high-energy shocks (3 patients) and combined therapy (3 patients). Intermediate or high-energy shocks terminated all induced VF episodes. During follow-up (2 to 12 months), there have been 2 noncardiac deaths. Electrical therapy was delivered in 7 patients, for VT (3 patients), VT and VF (3 patients) and indeterminate tachyarrhythmia (1 patient). All VT/VF episodes were successfully terminated, with 78 of 96 (81%) spontaneous VT episodes terminated by pacing. Follow-up reprogramming was required in 5 patients. It is concluded that successful application of individualized electrical therapy prescriptions in patients with VT/VF is feasible. Pacing therapies, which are effective for induced VT, can be reliably used for effective long-term spontaneous VT termination in conjunction with shock therapy and can permit reduced patient exposure to shock therapy. Thus, a programmable hybrid pacemaker cardioverter-defibrillator system provides nonthoracotomy implantation, effective VT/VF termination, demand ventricular pacing and noninvasive modes for arrhythmia induction, event monitoring and clinical trouble-shooting.

Electrophysiology and endocardial mapping of induced atrial fibrillation in patients with spontaneous atrial fibrillation

We analyzed the patterns of atrial activation and characterized the electrophysiologic properties of regional atrial sites in the, right atrium and left atrium at the onset of atrial fibrillation (AF) induced with programmed right atrial (RA) stimulation. Intraatrial conduction, atrial electrogram return cycle lengths for the first AF cycle, RA and left atrial (LA) activation maps during AF, and the stability and reproducibility of atrial activation sequences at AF onset and maintenance were analyzed in 23 patients with AF. Correlation of intracardiac electrograms with surface electrocardiographic morphology was attempted. Maximum intraatrial conduction delay for high RA premature beats was observed at the coronary sinus ostium (n = 15), His bundle region (n = 13) or interatrial septum (n = 15). The return cycle lengths for the first AF cycle showed increasing conduction delay with increasing prematurity of the last extrastimulus in most patients. Suprisingly, discrete atrial electrograms with regular or irregular cycle lengths were present at the onset of electrocardiographic documented coarse AF in 13 of 15 patients (87%). Fragmented or chaotic atrial activity were present in 2 of 15 patients (13%) in coarse AF but observed at > or = 1 atrial sites in 7 of 8 patients (88%) with fine AF (p = 0.001). The atrial activation sequence at the onset of the induced AF elicited by high RA extrastimuli usually showed the earliest activation site at the crista terminalis (9 patients) or interatrial septum (9 patients). In contrast, induced AF elicited from other RA sites usually showed earliest atrial activation at the septum (3 patients) or coronary sinus ostium (3 patients). Atrial activation sequences for the first induced AF cycle were usually reproducible in most patients. Atrial activation patterns during the first 10 cycles for AF were stable in RA and LA regions in 6 of 23 patients (260%) but demonstrated significant change(s) at > or = 1 region in 17 of 23 patients (74%) (p <0.05). We conclude that pacing induced AF elicited by RA premature beats commences as a regular or irregular rapid atrial tachycardia consistent with a transitional, but often organized, arrhythmia. The activation sequence and electrophysiologic behavior of the first induced AF cycle is consistent with intraatrial reentry and reproducible in most patients. More than 1 atrial activation sequence can sometimes be observed, emphasizing the dynamic nature of the initial RA reentrant circuits.

Effects of High-Frequency Atrial Pacing in Atypical Atrial Flutter and Atrial Fibrillation

Atypical atrial flutter has, hitherto, been relatively refractory totermination by rapid atrial pacing. High-frequency pacing (HFP) in theatrium, for termination of atrial flutter or atrial fibrillation (AF), andthe electrophysiologic effects related to it have not been examined. Weexamined the clinical efficacy, safety, and electrophysiologic mechanisms ofHFP using 50-Hz bursts at 10 mA applied at the high right atrium in patientswith atypical atrial flutter (group 1) or AF (group 2), using a prospectiverandomized study protocol. Four burst durations (500, 1000, 2000, and 4000ms) were applied at the high right atrium repetitively in random sequence in22 patients with spontaneous atrial flutter or AF. Local and distant rightand left atrial electrogram recordings were analyzed during and after HFP.HFP resulted in local and distant right and left atrial electrogramacceleration in 8 of 10 patients (80%) in group 1 but caused lessfrequent local atrial electrogram acceleration (6 of 12 patients) and nodistant atrial electrogram effects in group 2 (p < .05 versus group 1).The HFP protocol was effective in arrhythmia termination in 6 of 10patients in group 1 but in no patient in group 2 (p < .05 versus group1). Standard HFP protocol applied at the high right atrium can frequentlyalter atrial activation in both atria and can terminate atypical atrialflutter. Efficacy in AF is limited, probably due to limitedelectrophysiologic actions beyond the local pacing site.