Sequential Pacing Research Articles

Carbon monoxide exposure enhances arrhythmia after cardiac stress: involvement of oxidative stress

Arrhythmias following cardiac stress are a key predictor of death in healthy population. Carbon monoxide (CO) is a ubiquitous pollutant promoting oxidative stress and associated with hospitalization for cardiovascular disease and cardiac mortality. We investigated the effect of chronic CO exposure on the occurrence of arrhythmic events after a cardiac stress test and the possible involvement of related oxidative stress. Wistar rats exposed chronically (4weeks) to sustained urban CO pollution presented more arrhythmic events than controls during recovery after cardiac challenge with isoprenaline in vivo. Sudden death occurred in 22% of CO-exposed rats versus 0% for controls. Malondialdehyde (MDA), an end-product of lipid peroxidation, was increased in left ventricular tissue of CO-exposed rats. Cardiomyocytes isolated from CO-exposed rats showed higher reactive oxygen species (ROS) production (measured with MitoSox Red dye), higher diastolic Ca(2+) resulting from SR calcium leak and an higher occurrence of irregular Ca(2+) transients (measured with Indo-1) in comparison to control cells after a high pacing sequence. Acute treatment with a ROS scavenger (N-acetylcysteine, 20mmol/L, 1h) prevented this sequence of alterations and decreased the number of arrhythmic cells following high pacing. Chronic CO exposure promotes oxidative stress that alters Ca(2+) homeostasis (through RYR2 and SERCA defects) and thereby mediates the triggering of ventricular arrhythmia after cardiac stress that can lead to sudden death.

Improvement in pump function with endocardial biventricular pacing increases with activation time at the left ventricular pacing site in failing canine hearts

Recently, attention has been focused on comparing left ventricular (LV) endocardial (ENDO) with epicardial (EPI) pacing for cardiac resynchronization therapy. However, the effects of ENDO and EPI lead placement at multiple sites have not been studied in failing hearts. We hypothesized that differences in the improvement of ventricular function due to ENDO vs. EPI pacing in dyssynchronous (DYSS) heart failure may depend on the position of the LV lead in relation to the original activation pattern. In six nonfailing and six failing dogs, electrical DYSS was created by atrioventricular sequential pacing of the right ventricular apex. ENDO was compared with EPI biventricular pacing at five LV sites. In failing hearts, increases in the maximum rate of LV pressure change (dP/dt; r = 0.64), ejection fraction (r = 0.49), and minimum dP/dt (r = 0.51), relative to DYSS, were positively correlated (P < 0.01) with activation time at the LV pacing site during ENDO but not EPI pacing. ENDO pacing at sites with longer activation delays led to greater improvements in hemodynamic parameters and was associated with an overall reduction in electrical DYSS compared with EPI pacing (P < 0.05). These findings were qualitatively similar for nonfailing hearts. Improvement in hemodynamic function increased with activation time at the LV pacing site during ENDO but not EPI pacing. At the anterolateral wall, end-systolic transmural function was greater with local ENDO compared with EPI pacing. ENDO pacing and intrinsic activation delay may have important implications for management of DYSS heart failure.

Right ventricular pacing improves haemodynamics in right ventricular failure from pressure overload: an open observational proof-of-principle study in patients with chronic thromboembolic pulmonary hypertension

Right ventricular (RV) failure in patients with chronic thromboembolic pulmonary hypertension (CTEPH), and other types of pulmonary arterial hypertension is associated with right-to-left ventricle (LV) delay in peak myocardial shortening and, consequently, the onset of diastolic relaxation. We aimed to establish whether RV pacing may resynchronize the onsets of RV and LV diastolic relaxation, and improve haemodynamics. Fourteen CTEPH patients (mean age 63.7 ± 12.0 years, 10 women) with large (≥60 ms) RV-to-LV delay in the onset of diastolic relaxation (DIVD, diastolic interventricular delay) were studied. Temporary RV pacing was performed by atrioventricular (A-V) sequential pacing with incremental shortening of A-V delay to advance RV activation. Effects were assessed using tissue Doppler echocardiography and LV pressure-conductance catheter measurements in a subset of patients. Compared with right atrial pacing, RV pacing at optimal A-V delay (average 140 ± 22 ms, range 120-180 ms) resulted in significant DIVD reduction (59 ± 19 to 3 ± 22 ms, P < 0.001), and increase in LV stroke volume as measured by LV outflow tract velocity-time integral (14.9 ± 2.8 to 16.9 ± 3.0 cm, P < 0.001), along with enhanced global RV contractility and LV diastolic filling. Right-to-left ventricle resynchronization of the onset of diastolic relaxation results in stroke volume increase in CTEPH patients. Whether RV pacing may be a novel therapeutic target in RV failure following chronic pressure overload remains to be investigated.

Conduction Velocity Restitution of the Human Atrium—An Efficient Measurement Protocol for Clinical Electrophysiological Studies

Conduction velocity (CV) and CV restitution are important substrate parameters for understanding atrial arrhythmias. The aim of this work is to (i) present a simple but feasible method to measure CV restitution in-vivo using standard circular catheters, and (ii) validate its feasibility with data measured during incremental pacing. From five patients undergoing catheter ablation, we analyzed eight datasets from sinus rhythm and incremental pacing sequences. Every wavefront was measured with a circular catheter and the electrograms were analyzed with a cosine-fit method that calculated the local CV. For each pacing cycle length, the mean local CV was determined. Furthermore, changes in global CV were estimated from the time delay between pacing stimulus and wavefront arrival. Comparing local and global CV between pacing at 500 and 300 ms, we found significant changes in seven of eight pacing sequences. On average, local CV decreased by 20 ± 15% and global CV by 17 ± 13%. The method allows for in-vivo measurements of absolute CV and CV restitution during standard clinical procedures. Such data may provide valuable insights into mechanisms of atrial arrhythmias. This is important both for improving cardiac models and also for clinical applications, such as characterizing arrhythmogenic substrates during sinus rhythm.

A 2:1 AV Rhythm: An Adverse Effect of a Long AV Delay during DDI Pacing and Its Prevention by the Ventricular Intrinsic Preference Algorithm in DDD Mode

A 91-year-old woman received a dual-chamber pacemaker for sick sinus syndrome and intermittently abnormal atrioventricular (AV) conduction. The pacemaker was set in DDI mode with a 350-ms AV delay to preserve intrinsic ventricular activity. She complained of palpitation during AV sequential pacing. The electrocardiogram showed a 2:1 AV rhythm from 1:1 ventriculoatrial (VA) conduction during ventricular pacing in DDI mode with a long AV interval. After reprogramming of the pacemaker in DDD mode with a 250-ms AV interval and additional 100-ms prolongation of the AV interval by the ventricular intrinsic preference function, VA conduction disappeared and the patient's symptom were alleviated without increasing unnecessary right ventricular pacing.

Irregular Ventricular Activation Results in QT Prolongation and Increased QT Dispersion: A New Insight Into the Mechanism of AF-Induced Ventricular Arrhythmogenesis

Atrial fibrillation (AF) has been shown to be associated with increased risk of ventricular arrhythmias. We have previously shown reverse electrical remodeling of the ventricles following successful restoration of sinus rhythm in patients with persistent AF. The purpose of this study was to assess the relative role of irregular ventricular activation in mediating the previously observed changes. Twenty-two patients referred for an invasive electrophysiologic study were randomized to 30 minutes of regular or irregular atrioventricular (AV) sequential pacing at 100 beats per minute (bpm) with a programmed AV interval of 100 ms. Irregular pacing was triggered from prerecorded digital signal with a mean rate of 100 bpm, and a standard deviation of 150 ms (25% of the mean rate). In the regular pacing group, QT and QTc decreased from 448 ± 102 ms and 453 ± 105 ms to 428 ± 109 ms and 442 ± 104 ms, respectively (P < 0.001 for QT interval and P < 0.001 for QTc interval). There was no significant change in QT dispersion. In the irregular pacing group, QT and QTc increased from 477 ± 104 ms and 486 ± 78 ms to 489 ± 106 ms and 500 ± 106 ms (P < 0.01 for QT interval and P = 0.03 for QTc interval). In addition, there was a significant increase in QT dispersion from 50 ± 22 ms to 66 ± 22 ms (P = 0.001). Since the rate and pacing sites were similar between the groups, we attribute the repolarization changes in the irregular pacing group to the irregular activation of the ventricles. The detrimental effects of irregular pacing go beyond the hemodynamic changes and include electrical remodeling that favors an arrhythmogenic substrate.

Right Ventricular Infarction

Right Ventricular Infarction

Short- and Mid-Term Outcome of Combined Ganglionated Plexi (GP) Ablation and Radial Procedure for the Treatment of Atrial Fibrillation

We performed GP ablation combined with a radial procedure for the treatment of AF in 14 patients. A total of 35 sites at 5 anatomical GP areas were stimulated to identify active GP with marked vagal reflex during high frequency stimulation. The active GPs were ablated randomly one by one using sequential pacing and an ablation technique. Postoperative heart rate variability and surgical outcome at short- and mid-term follow-up was then examined. An average of 4.3±2.0 active GPs were identified in each patient. Atrial fibrillation recurred in 7 patients (50%) 10 days postoperatively. Heart rate variability showed that high-frequency spectral component was significantly smaller in the patients who retained in sinus rhythm compared to patients with recurring AF (20.6±12.7 vs 148.2±124.9, p<0.05). Thirteen patients (92%) restored sinus rhythm at discharge and maintained in sinus rhythm without recurrence of AF at a mean follow-up of 7.4±4.7 months. GP ablation combined with a radial procedure resulted in a satisfactory outcome at short- and mid-term follow-up.

Temporal evolution of the phase correction response in synchronization of taps with perturbed two-interval rhythms

Human sensorimotor synchronization is flexible but subject to temporal constraints. Previous research has shown that musicians tend to lose synchrony with target tones in an isochronous sequence when the sequence rate exceeds 8-10 Hz, presumably because phase correction ceases to function. The present study investigated directly the time required for an immediate phase correction response (PCR). Musicians tapped in synchrony with cyclic two-interval (short-long) rhythms, using the two hands in alternation. Perturbations were applied to the long interval, and the compensatory shift of the next tap (the PCR) was measured following the short interval, whose duration was varied from 100 to 300 ms. The PCR was found to increase gradually within this range, being nearly absent at 100 ms. Similar results were obtained when participants tapped only with the second tone in each rhythmic group, which confirms that the PCR is based on the preceding tone rather than on the preceding tap-tone asynchrony, and also when the second tone was omitted in the pacing sequence, which indicates that the PCR occurs automatically even when there is no synchronization target for the critical tap. These results extend earlier findings regarding rate limits of synchronization and also provide further support for an event-based phase resetting account of the PCR.

E0554 QRS duration changes during different VV intervals after cardiac resynchronisation therapy

IntroductionThe aim of this study was to investigate the influence of different VV intervals on QRS duration of surface ECG after cardiac resynchronisation therapy (CRT).Methods54 patients after CRT treatment due...

E0649 Long-term effects of RA-URIS pacing on left ventricular remodelling in patients with chronic heart dysfunction

ObjectiveTo assess the effects of RA-URIS dual chamber sequential pacing on left ventricular remodelling and cardiac function in SSS or AVB patients with chronic heart dysfunction.Methods32 patients with SSS or...

E0650 The effects of biventricular synchronous pacing on CBF, MVO2 and CWE in dogs

ObjectiveTo compare the effects of biventricular synchronous pacing with different pacing site on coronary Blood flow (CBF), myocardial oxygen consumption (MVO2) and cardiac work efficiency (CWE).MethodsRA-cHisB and RA-RVA sequential pacing,...

The impact of basal ganglia lesions on sensorimotor synchronization, spontaneous motor tempo, and the detection of tempo changes

The basal ganglia (BG) are part of extensive subcortico-cortical circuits that are involved in a variety of motor and non-motor cognitive functions. Accumulating evidence suggests that one specific function that engages the BG and associated cortico-striato-thalamo-cortical circuitry is temporal processing, i.e., the mechanisms that underlie the encoding, decoding and evaluation of temporal relations or temporal structure. In the current study we investigated the interplay of two processes that require precise representations of temporal structure, namely the perception of an auditory pacing signal and manual motor production by means of finger tapping in a sensorimotor synchronization task. Patients with focal lesions of the BG and healthy control participants were asked to align finger taps to tone sequences that either did or did not contain a tempo acceleration or tempo deceleration at a predefined position, and to continue tapping at the final tempo after the pacing sequence had ceased. Performance in this adaptive synchronization-continuation paradigm differed between the two groups. Selective damage to the BG affected the abilities to detect tempo changes and to perform attention-dependent error correction, particularly in response to tempo decelerations. An additional assessment of preferred spontaneous, i.e., unpaced but regular, production rates yielded more heterogeneous results in the patient group. Together these findings provide evidence for less efficient processing in the perception and the production of temporal structure in patients with focal BG lesions. The results also support the functional role of the BG system in attention-dependent temporal processing.

Cardiac resynchronization therapy or sequential pacing in failing Mustard?

The atrial switch (Mustard, Senning procedures) was one of the treatments of choice for repair of transposition of the great arteries from the early 1960s to the mid-1980s. A significant proportion of patients with atrial switch develops systemic (right) ventricular failure. A series of surgical therapeutic options exists to manage cardiac failure in this setting, and, more recently proposed, cardiac resynchronization therapy. We describe case report of a 30-year-old woman with congenital heart disease (CHD) and previous Mustard procedure who underwent upgrading from single chamber to dual-chamber pacemaker. The narrower native QRS did not correlate with a better synchrony status nor with a better cardiac output. Functional evaluation confirmed a better performance in DDD mode with short atrioventricular delay and broad QRS. Some echocardiographic and electrocardiographic parameters, such as ejection fraction and QRS duration, well established in adults' heart for selection of candidates to cardiac resynchronization therapy, are much less studied in CHD. Postoperative CHD may provide unique patterns of asynchrony with poorly predictable hemodynamic outcome.

Spatiotemporal Relations and Movement Trajectories in Visuomotor Synchronization

This work investigates how spatial and temporal aspects of rhythmic movements are affected by spatial and temporal components of a visual pacing sequence. Participants synchronized finger taps with three visual pacing sequences (Flash, High Finger, and Low Finger) at two tempi (500 ms and 400 ms interonset interval). The Flash sequence contained only temporal information, whereas the two Finger sequences contained apparent motion of different amplitudes. Participants' finger movements were recorded with a motion capture system, and movement trajectories and timing accuracy were analyzed. Results indicated that apparent motion facilitates visuomotor synchronization accuracy, which likely stems from tight perception-action links. Stimulus amplitude modulated tap amplitudes in the same direction, but this spatial assimilation did not adversely affect timing accuracy. Flexion times toward the target were significantly shorter than extension or dwell times, and could indicate a relatively ballistic movement trajectory. Local deviations of tap timing correlated with the movement trajectories from the preceding and following movement cycle. For example, after a late tap, the following movement cycle had lower amplitude and shorter extension and dwell times. This could signify the workings of error correction mechanisms that ensure stable synchronization.

Invasive Optimization of the LV Lead Position, Atrioventricular and Interventricular Intervals during Cardiac Resynchronization- Role of the VV Interval Determined by the Long Term Follow up in the Prospective Randomized Study

Cardiac resynchronization therapy has emerged as an important therapy for advanced systolic heart failure. Earlier studies demonstrate that simultaneous biventricular (BiV) pacing is superior to sequential BiV pacing. It has been demonstrated that acute changes of the VV and AV-delay in CRT patients has a significant impact on acute hemodynamics. The chronic functional effects of VV and AV-delay optimization with pressure volume catheters have not been systematically examined despite of their potential role for chronic functional improvement. Our trial is the first prospective randomized trial of patients with optimized LV lead position that compared patients with VV interval of 0 to patients with hemodynamically optimized VV interval. Our study was a single center randomized prospective trial in which 36 patients with New York Heart Association class III or IV heart failure, an LV ejection fraction 35%, and a QRS duration 150 ms. The control group had 18 patients (8 ICM, 10 NICM) with hemodynamicaly optimized LV lead position and AV interval VV randomized to 0. The invasively optimized group (IG) consisted of 18 patients, 8 ICM, 10 NICM. (mean NYHA class, 2.7; mean QRS interval, 152 ms;). For both groups the LV was divided into 19 segments comparable to a bulls eye image from nuclear perfusion imaging. LV leads were placed in all accessible segments and used for pacing while the pressure-volume loops were recorded with the conductance catheter. The optimal LV pacing site was determined by an increase in stroke volume and LVdP/dt(max), followed by A-V and V-V timing optimization. Relative to the baseline, optimal left ventricular lead position significantly increased stroke volume (+ 37%, P = .01), maximal LV Dp/dt (+ 22%, P = .02), ejection fraction (+ 35%, P = .05), and stroke work (+ 60%, P = .05) and reduced end-systolic volume (-5%, P = .05). VV in optimized group was 40 msec LV first in 80% of cases. Improvement in ECHO parameters after 6, 12 months of follow up correlated with acute increase in stroke volume. Patients were followed clinically at 3,6 and 12 month intervals with echo and QOL questionnaire. Compared to control, IG had a higher increase in EF (+ 15% Vs. + 12%) and a decrease of EDV (23% vs. 18%) and ESV (24% Vs 20%). Conclusions: Biventricular pacing with hemodynamically optimized VV interval was associated with a greater improvement in LV size and function.

Sequential biventricular pacing improves regional contractility, longitudinal function and dyssynchrony in patients with heart failure and prolonged QRS

AimsBiventricular pacing (BiP) is an effective treatment in systolic heart failure (HF) patients with prolonged QRS. However, approximately 35% of the patients receiving BiP are classified as non-responders. The aim of this study is to evaluate the acute effects of VV-optimization on systolic heart function.MethodsTwenty-one HF patients aged 72 (46-88) years, QRS 154 (120-190) ms, were studied with echocardiography, Tissue Doppler Imaging (TDI) and 3D-echo the first day after receiving a BiP device. TDI was performed; during simultaneous pacing (LV-lead pacing 4 ms before the RV-lead) and during sequential pacing (LV 20 and 40 ms before RV and RV 20 and 40 ms before LV-lead pacing). Systolic heart function was studied by tissue tracking (TT) for longitudinal function and systolic maximal velocity (SMV) for regional contractility and signs of dyssynchrony assessed by time-delays standard deviation of aortic valve opening to SMV, AVO-SMV/SD and tissue synchronization imaging (TSI).ResultsThe TT mean value preoperatively was 4,2 ± 1,5 and increased at simultaneous pacing to 5,0 ± 1,2 mm (p < 0,05), and at best VV-interval to 5,4 ± 1,2 (p < 0,001). Simultaneous pacing achieved better TT distance compared with preoperative in 16 patients (76%). However, it was still higher after VV-optimization in 12 patients 57%. Corresponding figures for SMV were 3,0 ± 0,7, 3,5 ± 0,8 (p < 0,01), and 3,6 ± 0,8 (p < 0,001). Also dyssynchrony improved.ConclusionsVV-optimization in the acute phase improves systolic heart function more than simultaneous BiP pacing. Long-term effects should be evaluated in prospective randomized trials.

Rate-dependent measures of repolarization predict inducibility of ventricular arrhythmias

The aim of this study was to compare the rate-dependent measures of repolarization in patients with and without inducible ventricular arrhythmias, and so to assess the potential arrhythmogenic role of rate-dependent heterogeneities in cardiac repolarization. Two groups of patients were studied during invasive electrophysiological procedures for standard clinical indications. A normal group (n = 17) with supraventricular tachycardia, structurally normal hearts and no inducible ventricular arrhythmias (PES-) and an inducible group (n = 13) with inducible ventricular arrhythmias (PES+). In each patient, we delivered a series of S1-S2 pacing sequences with a baseline S2 of 500 ms, which was progressively reduced. At the same time, a 12-lead electrocardiogram (ECG) was recorded. T-waves were extracted from each ECG recording, and 12 different T-wave measures were obtained from each patient across a range of coupling intervals. These included conventional measures, and those obtained from principal component analysis (PCA) of repolarization waveforms. At baseline S2, there was no significant difference between the PES- and PES+ using conventional T-wave measures. There were significant differences at baseline S2 between groups using PCA-derived measures. These differences showed rate dependence and were larger at shorter coupling intervals. Two dynamic ECG measurements identified subjects who were inducible during PES; maximum relative T-wave residuum >0.10 (odds ratio: 38.5, 95% CI: 4.7-318.5; P < 0.001) and maximum T-wave shape index <0.007 (odds ratio: 180.0, 95% CI: 10.2-3167.0; P < 0.001). T-wave shape index is rate dependent and discriminates between PES- and PES+ patients. We propose that patients with inducible arrhythmias have rate-dependent heterogeneity of repolarization which could be a useful tool for risk stratification.

Cardiac resynchronization therapy; the importance of evaluating cardiac metabolism

Cardiac resynchronization therapy; the importance of evaluating cardiac metabolism

Combined Atrial and Ventricular Antitachycardia Pacing as a Novel Method of Rhythm Discrimination

Inappropriate and unnecessary implantable cardioverter-defibrillator shocks continue to be highly prevalent. We prospectively evaluated a new algorithm for discriminating supraventricular (SVT) and ventricular (VT) tachycardias with 1:1 atrioventricular association that is based on the response of the arrhythmia to simultaneous or convergent dual-chamber antitachycardia pacing. Patients undergoing dual-chamber cardioverter-defibrillator implantation were randomized to the simultaneous atrioventricular and convergent atrioventricular arms with crossover at 3 months. Sixty-three patients had 1407 1:1 antitachycardia pacing sequences suitable for analysis (1381 1:1 SVT episodes in 32 patients and 26 1:1 VT episodes in 6 patients). Antitachycardia pacing terminated 66 of 1381 SVT (5%; generalized estimating equations adjusted, 23.8%) and 20 of 26 VT (77%; generalized estimating equation adjusted, 68.6%) episodes. After the exclusion of sinus tachycardia, the new software terminated 40 of 57 (70%; generalized estimating equation adjusted, 70.2%) SVT episodes. The new algorithm terminated or correctly classified 1379 of 1381 SVT sequences for an overall specificity of 99.9% (generalized estimating equation adjusted, 99.8%) and 23 of 26 VT for an overall sensitivity of 88.5% (generalized estimating equation adjusted, 82.1%). There were no statistically significant differences between the simultaneous and the convergent atrioventricular antitachycardia pacing sequences in their ability to confirm VT or reject SVT. No significant proarrhythmias were noted. We describe here a new pacing algorithm in dual-chamber defibrillators that can terminate arrhythmias or discriminate between 1:1 SVT and VT if the arrhythmia persists. Testing this new algorithm in larger patient populations is warranted. CLINICAL TRIAL REGISTRATION INFORMATION- URL: http://ftp.resource.org/gpo.gov/register/2007/2007_15297.pdf. IDE No. G060230.