The preference for treatment of symptomatic bradycardia is transvenous right ventricular pacing combined with atrial synchronisation if applicable. In the case of congenital anomalies where no conduit is present between the peripheral veins and the right ventricle, it is not possible to place the ventricular pacing lead in the right ventricle. Also the presence of an artificial valve in the tricuspid position excludes placement of an endocardial right ventricular pacing lead. Since the introduction of biventricular pacing, new guiding catheters and leads used as a transvenous route for left ventricular pacing are available. We report implantation of a ventricular pacing lead in the great cardiac vein for permanent ventricular pacing in a patient with a tricuspid valve prosthesis.
coronary sinus lead; tricuspid valve prosthesis; ventricular pacing
Cardiac memory refers to the observation that altered cardiac electrical activation results in repolarization changes that persist after the restoration of a normal activation pattern. Animal studies, however, have yielded disparate conclusions both regarding the spatial pattern of repolarization changes in cardiac memory and the underlying mechanisms. This study was undertaken to produce three dimensional images of the repolarization changes underlying long-term cardiac memory in humans.
Methods and Results
Nine adult subjects with structurally normal hearts and dual-chamber pacemakers were enrolled in the study. Non-invasive electrocardiographic imaging (ECGI) was used before and after one month of ventricular pacing to reconstruct epicardial activation and repolarization patterns. Eight subjects exhibited cardiac memory in response to ventricular pacing. In all subjects, ventricular pacing resulted in a prolongation of the activation recovery interval (a surrogate for action potential duration) in the region close to the site of pacemaker-induced activation from 228.4±7.6 ms during sinus rhythm to 328.3±6.2 ms during cardiac memory. As a consequence, increases are observed in both apical-basal and right-left ventricular gradients of repolarization resulting in a significant increase in the dispersion of repolarization.
These results demonstrate that electrical remodeling in response to ventricular pacing in human subjects results in action potential prolongation near the site of abnormal activation and a marked dispersion of repolarization. This dispersion of repolarization is potentially arrhythmogenic and, intriguingly, was less evident during continuous RV pacing, suggesting the novel possibility that continuous RV pacing at least partially suppresses pacemaker-induced cardiac memory.
action potentials; pacemakers; remodeling; T wave memory; cardiac memory
We hypothesized that LV segmental dyssynchrony, quantified by paradoxical systolic wall thinning, determines changes in global LV performance in a model of canine right ventricular pacing-induced dyssynchrony and the response to CRT.
Quantification of left ventricular (LV) dyssynchrony is important to assess the impact of cardiac resynchronization therapy (CRT).
Seven pentobarbital-anesthetized open-chest dogs had LV pressure-volume relations and mid-LV short-axis echocardiographic speckle tracking radial strain imaging during right atrial pacing (RA), right ventricular pacing (RV) to simulate left bundle branch block, and CRT using RV plus either LV free wall (CRTfw) and apical (CRTa) pacing. The area under the segmental LV time-radial strain positive and negative curves defined global thickening and thinning, respectively. Dyssynchrony was defined as the maximum time difference between earliest and latest peak segmental positive strain among 6 radial sites.
RA had minimal dyssynchrony (58±40 ms). RV induced both dyssynchrony (213±67 ms, *p<0.05) and reduced LV stroke work (SW)(67±51 mJ* p<0.05). CRTfw and CRTa decreased dyssynchrony (116±47 and 50±34 ms, respectively, * vs. RV) but only CRTa restored LV SW to RA levels. RV decreased global thickening (129±87%•msec) compared to RA (258±133%• ms p<0.05), whereas CRTfw and CRTa restored regional thickening to RA levels (194±83 and 230±76% •ms, respectively). The sum of thickening and thinning during RV (230±88 vs. 258±133%•ms*) correlated (r=0.98) with RA thickening, suggesting that all the loss of LV function was due to thinning.
Dyssynchrony causes proportional changes in regional LV wall thinning and global LV stroke work that were reversed by CRT, suggesting that dyssynchrony impairs LV systolic function by causing paradoxical regional wall thinning and that CRT effectiveness can be monitored by its reversal. Thus, monitoring paradoxical regional thinning reversal may be used to define CRT effectiveness.
canine model; cardiac resynchronization therapy; dyssynchrony; echocardiography; speckle tracking; ventricular performance
Objectives—To study the differences between endocardial bipolar and unipolar ventricular paced evoked responses and surface electrocardiograms.
Patients—10 patients with conduction system disease awaiting insertion of a permanent pacemaker were studied with temporary ventricular pacing from the right ventricular apex.
Main outcome measure—Comparison of the durations of the QRS complexes and QTa and QTe intervals of the endocardial bipolar paced evoked response and the surface electrocardiogram with those of the reference unipolar paced evoked response.
Results—By comparison with the unipolar reference, the mean durations of the QRS complexes of the bipolar signal and the surface electrocardiogram were 41·8% and 132·1% respectively. The mean QTa interval was 85·9% and 112·2% respectively and the mean QTe interval was 86·9% and 109·5% respectively. All these differences were significant. The amplitudes of the unipolar QRS complexes and T waves were significantly larger than those recorded in the bipolar configuration.
Conclusions—Differences between the unipolar and bipolar ventricular paced evoked responses are significant. The time course of the unipolar signal is closer to that of the surface electrocardiogram. This indicates that the unipolar paced evoked response does not reflect local electrophysiological events, as has been suggested previously.
Early problems after implantation of an endocardial electrode for permanent pacing occur in many patients. Difficulties can be anticipated in many of these patients and their management made much easier by a knowledge of the daily endocardial threshold obtained in patients with an implanted Elema Verio pacing unit by a simple non-invasive technique using a magnet and electrocardiogram. Twenty patients are described in whom permanent pacing with an Elema Vario unit was undertaken. The practical advantages of this unit can be readily seen in the patient who developes exit block or in the patient with obstructive airways disease, in whom frequent coughing or right ventricular hypertrophy may make stable electrode placement difficult. The chief advantage of the Elema Vario pacemaker is the extreme simplicity with which knowledge of the endocardial threshold can be obtained.
In cardiac resynchronisation therapy, failure to implant a left ventricular lead in a coronary sinus branch has been reported in up to 10% of cases. Although surgical insertion of epicardial leads is considered the standard alternative, this is not without morbidity and technical limitations. Endocardial left ventricular pacing can be an alternative as it has been associated with a favourable acute haemodynamic response compared with epicardial pacing in both animal and human studies. In this paper, we discuss left ventricular endocardial pacing and compare it with epicardial surgical implantation. Ease of application and procedural complications and morbidity compare favourably with epicardial surgical techniques. However, with limited experience, the most important concern is the still unknown long-term risk of thromboembolic complications. Therefore, for now endovascular implants should remain reserved for severely symptomatic heart failure patients and patients at high surgical risk of failed coronary sinus implantation.
Cardiac resynchronization therapy; Left ventricular pacing; Endocardial stimulation; Transseptal catheterization
Cardiac electromechanical dyssynchrony causes regional disparities in workload, oxygen consumption, and myocardial perfusion within the left ventricle. We hypothesized that such dyssynchrony also induces region-specific alterations in the myocardial transcriptome that are corrected by cardiac resynchronization (CRT).
Methods and Results
Adult dogs underwent left bundle branch ablation (LBBB) and right atrial pacing at 200 bpm for either 6 weeks (dyssynchronous heart failure, DHF, n=12) or 3 weeks followed by 3 weeks of resynchronization by bi-ventricular pacing at the same pacing rate (CRT, n=10). Control animals without LBBB were not paced (NF, n=13). At 6 weeks, RNA was isolated from the anterior and lateral LV walls and hybridized onto canine-specific 44K microarrays. Echocardiographically, CRT led to a significant decrease in the dyssynchrony index, while DHF and CRT animals had a comparable degree of LV dysfunction. In DHF, changes in gene expression were primarily observed in the anterior LV, resulting in increased regional heterogeneity of gene expression within the left ventricle. Dyssynchrony-induced expression changes in 1050 transcripts were reversed by CRT to levels of NF hearts (false discovery rate <5%). CRT remodeled transcripts with metabolic and cell signaling function and greatly reduced regional heterogeneity of gene expression compared with DHF.
Our results demonstrate a profound effect of electromechanical dyssynchrony on the regional cardiac transcriptome, causing gene expression changes primarily in the anterior LV wall. CRT corrected the alterations in gene expression in the anterior wall, supporting a global effect of biventricular pacing on the ventricular transcriptome that extends beyond the pacing site in the lateral wall.
Cardiac Resynchronization Therapy; Heart Failure; Gene Expression; Microarray
Short-term memory is an intrinsic property of paced cardiac myocytes that reflects the influence of pacing history, and not just the immediately preceding diastolic interval (DI), on the action potential duration (APD). Although it is recognized that short-term memory affects the dynamics of cardiac myocytes in general, and the onset of irregular cardiac rhythm in particular, its has never been adequately quantified or measured directly in experiments or numerical simulations, mainly due to the absence of appropriate techniques. As a result, very little is known about the rate- and species dependent behavior of short-term memory. In this study, we introduce a new approach that allows one to estimate how much short-term memory, MS, is present in the cardiac myocyte at different pacing rates. The new quantification is based on the fact that pacing history affects not only the APD, but the entire dynamics of paced cardiac myocytes, in particular the restitution curve. Using the patch clamp technique and numerical simulations, we measured short-term memory restitution—the dependence of MS on the cycle length—in isolated rabbit and guinea pig ventricular myocytes. In both species, MS is rate- and species-dependent, displaying a biphasic behavior as a function of cycle length. Moreover, our results indicate that there is a significant difference in MS measured between both species at small cycle lengths. Numerical simulations suggest that the kinetics of the rapidly activating delayed rectifier potassium current IKr is partially responsible for this difference.
Action potential duration; Short-term memory; Restitution; Cardiac myocytes
Little is known about the effect of cardiac resynchronization therapy (CRT) on endo- and epicardial ventricular activation. Noninvasive imaging of cardiac electrophysiology (NICE) is a novel imaging tool for visualization of both epi- and endocardial ventricular electrical activation.
NICE was performed in ten patients with congestive heart failure (CHF) undergoing CRT and in ten patients without structural heart disease (control group). NICE is a fusion of data from high-resolution ECG mapping with a model of the patient's individual cardiothoracic anatomy created from magnetic resonance imaging. Beat-to-beat endocardial and epicardial ventricular activation sequences were computed during native rhythm as well as during ventricular pacing using a bidomain theory-based heart model to solve the related inverse problem. During right ventricular (RV) pacing control patients showed a deterioration of the ventricular activation sequence similar to the intrinsic activation pattern of CHF patients. Left ventricular propagation velocities were significantly decreased in CHF patients as compared to the control group (1.6±0.4 versus 2.1±0.5 m/sec; p<0.05). CHF patients showed right-to-left septal activation with the latest activation epicardially in the lateral wall of the left ventricle. Biventricular pacing resulted in a resynchronization of the ventricular activation sequence and in a marked decrease of total LV activation duration as compared to intrinsic conduction and RV pacing (129±16 versus 157±28 and 173±25 ms; both p<0.05).
Endocardial and epicardial ventricular activation can be visualized noninvasively by NICE. Identification of individual ventricular activation properties may help identify responders to CRT and to further improve response to CRT by facilitating a patient-specific lead placement and device programming.
Left atrium (LA) plays an important role in left ventricular filling. It is well known that right ventricular apical pacing has unfavorable effects on ventricular systolic and diastolic performance. The aim of this study is to evaluate the LA mechanical functions with 2D echocardiography in patients with a permanent pacemaker after short time ventricular pacing.
Echocardiographic examination was performed in 38 patients (mean age 63.0± 10.9, 18 female) with dual chamber pacemakers or defibrillators (< 20% ventricular pacing within previous 6 months, all of them on sinus rhythm) before and after 4 hours > 90% ventricular pacing at 70 beats per minute in DDD mode with an optimal AV interval. Left atrial volumes (LAV) including at the time of mitral valve opening (Vmax), at closure (Vmin), and at the onset of atrial systole (Volp) were measured. The passive emptying, conduit, active emptying and total emptying volume, stroke volumes were also calculated.
No significant differences were noted at baseline and after pacing for absolute Vmax, Volp, passive emptying, conduit, active emptying, total emptying volumes as well as the volumes indexed to body surface area (p >0.05).
Short - time RV pacing seems to have no acute effects on left atrial mechanical functions.
Pacemaker; echocardiography; left atrial volume; left atrial function
A novel non-invasive imaging technique, the heart-model-based 3-dimensional cardiac electrical imaging (3DCEI) approach was previously developed and validated to estimate the initiation site (IS) of cardiac activity and the activation sequence (AS) from body surface potential maps (BSPMs) in a rabbit model. The aim of the present study was to validate the 3DCEI in an intact large mammalian model (swine) during acute ventricular pacing.
Methods and results
The heart-torso geometries were constructed from pre-operative MR images acquired from each animal. Body surface potential mapping and intracavitary non-contact mapping (NCM) were performed simultaneously during pacing from both right ventricular (intramural) and left ventricular sites (endocardial). Subsequent 3DCEI analyses were performed from the measured BSPMs. The estimated ISs were compared to the precise pacing locations and estimated ASs were compared to those recorded by the NCM system. In total, 5 RV and 5 LV sites from control and heart failure animals were paced and sequences of 100 paced beats were analyzed (10 for each site). The averaged localization error of the RV and LV sites were 7.3 ± 1.8 mm (n=50) and 7.0 ± 2.2 mm (n=50), respectively. The global 3-dimensional activation sequences throughout the ventricular myocardium were also derived. The endocardial ASs as a subset of the estimated 3-dimensional ASs were consistent with those reconstructed from the NCM system.
The present experimental results demonstrate that the noninvasive 3DCEI approach can localize the IS and estimate AS with good accuracy in an in vivo setting; under control, paced and/or diseased conditions.
3D Cardiac Electrical Imaging; Pacing; Electrocardiophysiology; body surface potential mapping; Noncontact mapping
Cardiac resynchronization therapy (CRT) is the therapy of choice for selected patients suffering from drug-refractory congestive heart failure and presenting an interventricular desynchronization. CRT is delivered by an implantable biventricular pacemaker, which stimulates the right atrium and both ventricles at specific timings. The optimization and personalization of this therapy requires to quantify both the electrical and the mechanical cardiac functions during the intraoperative and postoperative phases.
The objective of this paper is to evaluate the feasibility of the calculation of features extracted from endocardial acceleration (EA) signals and the potential utility of these features for the intraoperative optimization of CRT. Endocardial intraoperative data from one patient are analyzed for 33 different pacing configurations, including changes in the atrio-ventricular and inter-ventricular delays and different ventricular stimulation sites. The main EA features are extracted for each pacing configuration and analyzed so as to estimate the intra-configuration and inter-configuration variability. Results show the feasibility of the proposed approach and suggest the potential utility of EA for intraoperative monitoring of the cardiac function and defining optimal, adaptive pacing configurations.
To investigate the contribution of right ventricular (RV) pacing sites to the cardiac function, this study compares plasma B-type natriuretic peptide (BNP) levels during RV septal and apical pacing in patients implanted with a pacemaker.
Materials and Methods and Results:
Seventy-four consecutive patients with indication for permanent pacing were included. To provide for the possibility of appropriate subgroup analyses, patients were stratified according to their pacing mode into two groups: Those with dual chamber DDD(R)/VDD pacemakers (41 patients, mean age 54.1±18.4 years), and those with single chamber VVI pacemakers (33 patients, mean age 60.6±18.4 years). A prospective single-blinded randomized design was used. Randomization (1:1 way) was between lead placement on the RV septum or RV apex and occurred during the implant in both groups. Compared to baseline, a significant decrease in BNP (429.8±103 pg/ml and 291.7±138 pg/ml, respectively) levels was observed during DDD(R) /VDD pacing after two months. In contrast, during VVI (R) pacing, a significant increase in BNP levels was observed (657.5±104 pg/ml and 889.5±139 pg/ml, respectively). To determine the impact of pacing sites on cardiac function, we assessed the changes in BNP levels in each group separately. Despite the significant difference in the pattern of changes between the two groups (P < 0.02), no significant changes were observed within groups regarding the acute effect of the pacing site (RV apex vs. RV septal) on BNP levels (P=NS).
Our main result showed no significant differences between pacing sites and concluded that hemodynamic improvement could be substantially influenced by pacing mode, more than by pacing site.
B-type natriuretic peptide; right ventricular apical pacing; right ventricular septal pacing
Cardiac resynchronization therapy has been most typically achieved by biventricular stimulation. However, left ventricular (LV) free-wall pacing appears equally effective in acute and chronic clinical studies. Recent data suggest electrical synchrony measured epicardially is not required to yield effective mechanical synchronization, whereas endocardial mapping data suggest synchrony (fusion with intrinsic conduction) is important. To better understand this disparity, we simultaneously mapped both endocardial and epicardial electrical activation during LV free-wall pacing at varying atrioventricular delays (AV delay 0–150 ms) in six normal dogs with the use of a 64-electrode LV endocardial basket and a 128-electrode epicardial sock. The transition from dyssynchronous LV-paced activation to synchronous RA-paced activation was studied by constructing activation time maps for both endo- and epicardial surfaces as a function of increasing AV delay. The AV delay at the transition from dyssynchronous to synchronous activation was defined as the transition delay (AVt). AVt was variable among experiments, in the range of 44–93 ms on the epicardium and 47–105 ms on the endocardium. Differences in endo- and epicardial AVt were smaller (−17 to +12 ms) and not significant on average (−5.0 ± 5.2 ms). In no instance was the transition to synchrony complete on one surface without substantial concurrent transition on the other surface. We conclude that both epicardial and endocardial synchrony due to fusion of native with ventricular stimulation occur nearly concurrently. Assessment of electrical epicardial delay, as often used clinically during cardiac resynchronization therapy lead placement, should provide adequate assessment of stimulation delay for inner wall layers as well.
resynchronization; mapping; heart failure
The pacing site has been shown to influence functional improvement with cardiac resynchronization therapy. We evaluated the effects of the pacing site on left ventricular (LV) function in an animal model.
Methods and Results
Equilibrium radionuclide angiography was acquired in sinus rhythm (NSR) and with ventricular pacing, from three pacing sites in seven normal and eight infarcted dogs. QRS duration, electrical activation pattern, wall motion, LV ejection fraction (EF), synchrony of ventricular contraction, and mean arterial pressure (MAP), were related to the pacing site and infarct size, during each of 120 episodes. Little changed during pacing in normals. In infarcted dogs, LV wall motion, and synchrony worsened, LVEF and MAP often fell. These changes related to altered activation patterns which were influenced by the pacing site but were not related to infarct size.
Hemodynamic and functional LV changes after infarction were found to vary with the pacing site and associated conduction and synchrony.
Ventricular function; pacing; electrophysiology; synchrony
Some authors recommend avoiding fusion with left ventricular (LV) intrinsic depolarization during cardiac resynchronization therapy (CRT). If fusion is still present during optimized biventricular (Biv) pacing and its long-term effects on the response to CRT are currently unknown. The aim of the study was to analyse the endocardial LV activation pattern induced by echocardiographically optimized Biv pacing and its influence on LV reverse remodelling.
Methods and results
Contact electro-anatomical mapping was performed in 15 heart failure (HF) patients with left bundle branch block and echocardiographically optimized CRT (seven ischaemic aetiology, 64 ± 8 years, three women, New York Heart Association class 3 ± 0.4, LV ejection fraction 25 ± 5%). Left ventricular activation maps were performed in sinus rhythm (SR), during DDD right ventricular apical (RVA) and optimized Biv pacing. Fusion with intrinsic rhythm during pacing was considered when LV septal activation was produced at least partially by intrinsic depolarization, when compared with LV activation map during SR. Patients were considered responders to CRT if they had ≥10% reduction in LV end-systolic volume (LVESV) after 6 months of CRT. During SR, the LV breakthrough was mid-septal (n = 12), basal septum (n = 2), and apical (n = 1). During RVA pacing, LV breakthrough shifted apical in all patients. Right ventricular apical/Biv pacing proved fusion with intrinsic depolarization in 8 of 15 patients. The PR interval was shorter in patients with fusion RVA/Biv pacing (164 ± 24 vs. 234 ± 55 ms, P = 0.006). There was a trend for shorter LV activation time (LVat) in patients with fusion during RVA pacing (87 ± 33 vs. 113 ± 21 ms, P = 0.08) as well as during optimized Biv pacing (83 ± 18 vs. 104 ± 24 ms, P = 0.07), although LVat was similar in SR (100 ± 22 vs. 106 ± 20, P = NS). In patients with fusion, 6 months responder rate was significantly higher (100 vs. 28.5%, P < 0.007) as was the degree of LVESV reduction (39 ± 17 vs. 1.0 ± 14%, P < 0.001).
Biventricular pacing with fusion may substantially increase the structural responder rate probably by shortening LVat.
Cardiac resynchronization therapy; RVA pacing; Fusion; Activation time
Aims. This study evaluated feasibility and safety of implanting the polyester-coated nitinol ventricular septal defect occluder (pcVSDO) in the canine model. Methods and Results. VSD models were successfully established by transseptal ventricular septal puncture via the right jugular vein in 15 out of 18 canines. Two types of VSDOs were implanted, either with pcVSDOs (n = 8) as the new type occluder group or with the commercial ventricular septal defect occluders (VSDOs, n = 7, Shanghai Sharp Memory Alloy Co. Ltd.) as the control group. Sheath size was 10 French (10 Fr) in two groups. Then the general state of the canines was observed after implantation. ECG and TTE were performed, respectively, at 7, 30, 90 days of follow-up. The canines were sacrificed at these time points for pathological and scanning electron microscopy examination. The devices were successfully implanted in all 15 canines and were retrievable and repositionable. There was no thrombus formation on the device or occurrence of complete heart block. The pcVSDO surface implanted at day 7 was already covered with neotissue by gross examination, and it completed endothelialization at day 30, while the commercial VSDO was covered with the neotissue in 30th day and the complete endothelialization in 90th day. Conclusion. The study shows that pcVSDO is feasible and safe to close canine VSD model and has good biocompatibility and shorter time of endothelialization.
Pacing in children with congenital heart disease often requires alternate approaches to standard transvenous pacing. The surgical approach used to implant the pacemaker leads has been shown to impact lead survival. There is a paucity of pediatric literature describing the experience using a left thoracotomy approach.
To report on short- and mid-term experiences with pacemaker implant via the left thoracotomy approach in children with complex congenital heart disease.
METHODS AND RESULTS
Data were abstracted retrospectively from patients’ hospital charts. To date, the left thoracotomy technique has been used in 11 patients with complex heart disease, with a median of three prior cardiac operations. The median patient age was five years (range of two months to 23 years of age). The pacing indications were acquired postoperative atrioventricular block (n=5), sinus node dysfunction (n=5) and long QT syndrome (n=1). There were no intraoperative complications or long-term complications from this approach. The pacing thresholds at implant and follow-up were acceptable in all patients. One patient died in follow-up for reasons unrelated to the pacemaker or arrhythmia.
The placement of epicardial pacemaker leads via the left thoracotomy approach is a safe and effective alternative to transvenous pacing in pediatric patients with complex congenital heart disease.
Arrhythmia; Congenital heart disease; Pacemakers; Pediatrics
Speckle tracking imaging is a promising new echocardiographic method to assess left ventricular (LV) mechanical dyssynchrony. Our aim was to assess a new speckle tracking regional strain algorithm by comparison to angle corrected tissue Doppler (TD) in an animal model of left bundle branch block (LBBB) and cardiac resynchronization therapy (CRT).
Methods and Results
Ten open chest dogs had routine grayscale and tissue Doppler images of the mid-left ventricular (LV) short-axis plane. Electrical activation was altered by pacing from right ventricular (RV), LV free wall, and biventricular sites to create various degree of mechanical dyssynchrony and alter regional function. Segmental time-to-peak strain, peak strain and frame-by-frame strain were measured by angle corrected TD, TD M-mode and by speckle tracking on the same digital cineloop. Of 240 possible paired tissue Doppler and speckle tracking segments, data were available for 222 segments (93%); images with catheter artifacts were prospectively excluded. Comparative overall time-to-peak strain by each method correlated well: r = 0.96, bias=−6 ± 20 ms. Of 80 possible paired M-mode tissue Doppler and speckle tracking segments, strain data were available for 76 segments (95%). Comparative overall time-to-peak strain, peak strain and frame-by-frame strain analysis in 1012 frames by each method correlated well: r=0.98, bias of 1±14ms; r=0.82, bias of 3±7%; and r=0.91, bias of 0±6% respectively.
Regional strain analysis using echocardiographic speckle tracking radial strain strongly correlated with strain by angle-corrected tissue Doppler imaging in an animal model of dyssynchrony. Speckle tracking radial strain has potential for clinical applications.
echocardiography; electrical stimulation; pacing; ventricular function
A patient with complete atrioventricular block was fitted with a temporary endocardial pacing wire via a right subclavian percutaneous approach. The result was initially satisfactory, but within a few days radiography for left-sided chest pain showed pneumopericardium. A permanent epicardial pacing system was therefore substituted and she remained well for three months. She was then admitted for syncope: the pacemaker was failing to capture, and radiography showed pericardial and pleural effusion. A new permanent endocardial pacing system using a wedged electrode was inserted and she made an uncomplicated recovery. Pneumopericardium complicating endocardial pacing has apparently not been reported before. Presumably the electrode had penetrated both the right ventricle and the pericardium into the adjacent lung.
A fundamental description of pacemaker systems which are commercially available or in clinical validation is given as a background for their application in a series of 62 consecutive patients presenting over a period of 1 year for permanent cardiac pacing. The patients (23 (37%) sick sinus syndrome, 38 (61%) atrioventricular block, and 1 ventricular tachycardia) were studied electrophysiologically and haemodynamically to allow the appropriate application of a pacemaker system. In sick sinus syndrome, 8 patients had permanent atrial pacing, 14 ventricular pacing, and 1 atrioventricular sequential pacing; in atrioventricular block, 8 patients had atrial synchronous ventricular inhibited pacing and the remaining 30 had ventricular pacing. A high incidence of atrial fibrillation, 9 patients, and abnormal sinus node function, 15 patients, precluded wider use of atrial synchrony. The results show benefit in acute haemodynamic studies of using systems including atrial sensing and/or pacing, and with greater availability of atrioventricular sequential and still more advanced pacemakers with dual sensing as well as dual pacing the majority of patients may be offered this benefit.
Spinal cord stimulation (SCS) has been shown to modulate atrial electrophysiology and confer protection against ischemia and ventricular arrhythmias in animal models.
To determine whether SCS reduces the susceptibility to atrial fibrillation (AF) induced by tachypacing (TP).
In 21 canines, upper thoracic SCS systems and custom cardiac pacing systems were implanted. Right atrial and left atrial effective refractory periods were measured at baseline and after 15 minutes of SCS. Following recovery in a subset of canines, pacemakers were turned on to induce AF by alternately delivering TP and searching for AF. Canines were randomized to no SCS therapy (CTL) or intermittent SCS therapy on the initiation of TP (EARLY) or after 8 weeks of TP (LATE). AF burden (percent AF relative to total sense time) and AF inducibility (percentage of TP periods resulting in AF) were monitored weekly. After 15 weeks, echocar-diography and histology were performed.
Effective refractory periods increased by 21 ±14 ms (P ±.001) in the left atrium and 29 ±12 ms (P ±.002) in the right atrium after acute SCS. AF burden was reduced for 11 weeks in EARLY compared with CTL (P ±.05) animals. AF inducibility remained lower by week 15 in EARLY compared with CTL animals (32% ±10% vs 91% ±6%; P <.05). AF burden and inducibility were not significantly different between LATE and CTL animals. There were no structural differences among any groups.
SCS prolonged atrial effective refractory periods and reduced AF burden and inducibility in a canine AF model induced by TP. These data suggest that SCS may represent a treatment option for AF.
Atrial fibrillation; Spinal cord stimulation; Atrial tachypacing animal models
Previous studies showed that overexpression of sarco-endoplasmic reticulum calcium ATPase (SERCA2a) in a variety of heart failure (HF) models was associated with greatly enhanced cardiac performance. However, it still undefined the effect of SERCA2a overexpression on the systemic inflammatory response and neuro-hormonal factors.
A rapid right ventricular pacing model of experimental HF was used in beagles. Then the animals underwent recombinant adeno-associated virus 1 (rAAV1) mediated gene transfection by direct intra-myocardium injection. HF animals were randomized to receive the SERCA2a gene, enhanced green fluorescent protein (control) gene, or equivalent phosphate buffered saline. Thirty days after gene delivery, the cardiac function was evaluated by echocardiographic testing. The protein level of SERCA2a was measured by western blotting. The proteomic analysis of left ventricular (LV) sample was determined using two-dimensional (2-D) gel electrophoresis and MALDI-TOF-MS. The serum levels of the systemic inflammatory and neuro-hormonal factors were assayed using radioimmunoassay kits.
The cardiac function improved after SERCA- 2a gene transfer due to the significantly increased SERCA2a protein level. Beagles treated with SERCA2a had significantly decreased serum levels of the inflammatory markers (interleukin-6 and tumor necrosis factor-α) and neuro-hormonal factors (brain natriuretic peptide, endothelin-1 and angiotensin II) compared with HF animals. The myocardial proteomic analysis showed that haptoglobin heavy chain, heat shock protein (alpha-crystallin-related, B6) were down-regulated, and galectin-1 was up-regulated in SERCA2a group compared with HF group, companied by up-regulated contractile proteins and NADH dehydrogenase.
These findings demonstrate that regional intramyocardial injections of rAAV1-SERCA2a vectors may improve global LV function, correlating with reverse activation of the systemic inflammatory, excessive neuroendocrine factors and the stress-associated myocardial proteins, suggesting that the beneficial effects of SERCA2a gene transfer may involve the attenuation of stress-associated reaction.
Heart failure; Sarco-endoplasmic reticulum calcium ATPase; Gene transfer; Stress reaction; Neuro-hormonal factors
Single chamber ventricular pacing (VVI) may be associated with a group of adverse symptoms known as the pacemaker syndrome. Cough is an unusual but recognised feature of the pacemaker syndrome. A patient with a VVI permanent pacemaker experienced a disturbing cough during VVI pacing. There were no other symptoms associated with the pacemaker syndrome. The effects of short-term ventricular pacing on the cough were examined while the subject was standing and lying. After control recordings, the pulse generator was programmed to either VVI 50 beats/min or 90 beats/min and recordings made over 60 seconds. There was an interval of 60s between recordings. Overall, five recording periods at VVI of 50 beats/min and VVI of 90 beats/min were made in random order. The patient was blinded to the order of programming. The recordings were repeated with the subject lying. Cough was not found during normal sinus rhythm. During VVI pacing the patient experienced a tickling sensation in the throat associated with intermittent coughing. The number of coughs decreased during each successive recording period. The pacing cough reflex was enhanced when the patient was lying down. The mechanism of cough during VVI pacing is uncertain. The findings suggest a possible role for afferent vagal receptors from the airways.
OBJECTIVE—To determine whether permanent cardiac pacing could prevent syncope and seizures in children with frequent severe neurally mediated syncope, and if so whether dual chamber pacing was superior to single chamber ventricular pacing.
METHODS—Dual chamber pacemakers were implanted into 12 children (eight male, four female) aged 2-14 years (median 2.8 years) with frequent episodes of reflex anoxic seizures and a recorded prolonged asystole during an attack. The pacemaker was programmed to sensing only (ODO), single chamber ventricular pacing with hysteresis (VVI), and dual chamber pacing with rate drop response (DDD) for four month periods, with each patient allocated to one of the six possible sequences of these modes, according to chronological order of pacemaker implantation. The parent and patient were blinded to the pacemaker mode and asked to record all episodes of syncope or presyncope ("near miss" events). The doctor analysing the results was blinded to the patient and pacemaker mode.
RESULTS—One patient was withdrawn from the study after the pacemaker was removed because of infection. In the remaining children, both dual chamber and single chamber pacing significantly reduced the number of syncopal episodes compared with sensing only (p = 0.0078 for both). VVI was as effective as DDD for preventing syncope, but DDD was superior to VVI in reducing near miss events (p = 0.016).
CONCLUSIONS—Permanent pacing is an effective treatment for children with severe neurally mediated syncope and reflex anoxic seizures. VVI is as effective as DDD in preventing syncope and seizures, but DDD is superior in preventing overall symptoms.
Keywords: syncope; reflex anoxic seizures; pacing; paediatric cardiology