Diagnostic tools for atrial tachyarrhythmias in implantable pacemakers: a review of technical options and pitfalls

Background. Correct pacemaker (PM) diagnosis of paroxysmal atrial tachyarrhythmias is crucial for their prevention and intervention with specific atrial pacing programmes. The PM mode switch to only ventricular pacing after detection of atrial tachyarrhythmias is often used as the parameter to quantify the ‘burden’ of atrial tachyarrhythmias. Objectives. This review addresses potential errors in the detection and diagnosis of atrial tachyarrhythmias, sometimes resulting in incorrect mode switches. The interpretation of PM-stored data of patients with atrial tachyarrhythmias and the results of trials of pace prevention and intervention can be better appreciated with more insight into the technical options and pitfalls. Results. Literature and clinical experience demonstrate that the correctness of PM-derived diagnosis of atrial tachyarrhythmias depends on 1) the sensitivity setting to detect the onset and perpetuation of atrial tachyarrhythmias frequently characterised by variable and low-voltage signals, 2) the rejection of far-field R wave sensing by the atrial sense amplifier, 3) the facility for verification of mode switches by a high-quality intracardiac registration of the nonmodified atrial electrogram. The configuration of the atrial lead also contributes to the diagnostic performance of the PM. Conclusion. Not only pacing algorithms and diverse technical PM features but also the atrial lead configuration are currently the limiting factors to the fully reliable, automated detection and diagnosis of atrial tachyarrhythmias. If these technical shortcomings can be improved, better signal processing will result. Then atrial pacing to prevent or suppress atrial tachyarrhythmias will be more justified. (Neth Heart J 2008;16:201-10.)     

Plasma and atrial content of atrial natriuretic factor in cardiomyopathic hamsters

Immunoreactive atrial natriuretic factor (IR-ANF) was measured in plasma and atrial extracts from normal and cardiomyopathic Syrian golden hamsters. Plasma IR-ANF was increased from 84.8 ± 9.8 pg/ml(n = 17) to 234 ± 23 (n = 25; P<.0001) in hamsters with moderate failure, and to 1085 ± 321 pg/ml (n = 10; P<.02) in animals with severe failure. Plasma IR-ANF increased with increased atrial hypertrophy. Atrial IR-ANF content was essentially the same in normal animals and in those with moderate heart failure (3.06 ± 0.28 vs 3.17 ± 0.19 μg/100 g body wt., P<.001) and lower in the majority of those with severe failure (1.82 μg/100 g body wt., P<.001). The elevations of IR-ANF in plasma are similar to those seen in patients with congestive heart failure. Our studies do not support bioassay results showing a deficiency of atrial ANF content as being important in the congestive heart failure associated with cardiomyopathy in the hamster.     

The effects of intraoperative dexamethasone on left atrial function and postoperative atrial fibrillation in cardiac surgical patients

Postoperative new-onset atrial fibrillation (PNAF) is very common after cardiac surgery and postoperative inflammation may contribute to PNAF by inducing atrial dysfunction. Corticosteroids reduce inflammation and may thus reduce atrial dysfunction and PNAF development. This study aimed to determine whether dexamethasone protects against left atrial dysfunction and PNAF in cardiac surgical patients. Cardiac surgical patients were randomised to a single dose of dexamethasone (1 mg.kg⁻¹) or placebo after inducing anaesthesia. Transoesophageal echocardiography was performed in patients before and after surgery. Primary outcome was left atrial total ejection fraction (LA-TEF) after sternal closure; secondary outcomes included left atrial diameter and PNAF. 62 patients were included. Baseline characteristics were well balanced. Postoperative LA-TEF was 36.4 % in the dexamethasone group and 40.2 % in the placebo group (difference −3.8 %; 95 % confidence interval (CI) -9.0 to 1.4 %; P = 0.15). Postoperative left atrial diameter was 4.6 and 4.3 cm, respectively (difference 0.3; 95 % CI −0.2 to 0.7; P = 0.19). The incidence of PNAF was 30 % in the dexamethasone group and 39 % in the placebo group (P = 0.47). Intraoperative high-dose dexamethasone did not protect against postoperative left atrial dysfunction and did not reduce the risk of PNAF in cardiac surgical patients.     

Energetic metabolism during acute stretch-related atrial fibrillation

Background and methods Perturbations in energetic metabolism and impaired atrial contractility may play an important role in the pathogenesis of atrial fibrillation (AF). Besides, atrial stretch is commonly associated with AF. However, the atrial energetics of stretch-related AF are poorly understood. Here, we measured indicators of energy metabolism during acute stretch-related AF. PCr, adenine nucleotides, and derivatives concentrations as well as the activity of the F₀F₁-ATPase and Na,K-ATPase were obtained after 1 h of stretch and/or AF in isolated rabbit hearts and compared to control hearts without stretch and AF. Results After 1 h of stretch-related AF, the total adenine nucleotides’ pool was significantly lower (42.2 ± 2.6 vs. 63.7 ± 8.3 μmol/g protein in control group, P < 0.05) and the PCr/ATP ratio significantly higher (2.3 ± 0.3 vs. 1.1 ± 0.1 in control group P < 0.05), because of ATP, ADP, and AMP decrease and PCr increase. The sum of high-energy phosphate compounds did not change. There were no significant differences in F₀F₁-ATPase nor Na,K-ATPase activity between the groups. Conclusions Results show that in this experimental model, acute stretch-related AF induces specific modifications of atrial myocytes energetics that may play a pivotal role in the perpetuation of the arrhythmia.     

Nonlinear synchronization assessment between atrial and ventricular activations series from the surface ECG in atrial fibrillation

Atrial fibrillation (AF) is the most common form of arrhythmia encountered in clinical practice. Its presence causes a rapid and irregular ventricular response, being the topic of intensive research in rate control therapies of AF. To this respect, recent studies suggest that ventricular response is notably influenced by atrial activity (AA) temporal organization. However, the interdependency between atrial and ventricular activations has not been adequately explored to date in real-life AF patients. The present work introduces a novel methodology to quantitatively assess synchronization and coupling between real atrial and ventricular activation series. Furthermore, the method operates on surface ECG recordings, thus providing an easy and cost-effective way to be applied. The method is based on a nonlinear index, such as cross-sample entropy (CSE), which estimates the conditional probability to find similar patterns within both activation series. The study has been carried out on patients with paroxysmal and persistent AF in order to be applied over atrial activation series with different properties in their organization. Results showed a statistically significant positive correlation between AA organization and the synchronization between atrial and ventricular activations (R = 0.53, p < 0.01). Furthermore, higher CSE values were observed for persistent (0.759 ± 0.053) than for paroxysmal AF episodes (0.662 ± 0.091), thus suggesting more synchronization between atrial and ventricular activations in paroxysmal AF. As a consequence, CSE provided findings consistent with previous works and could be used to reveal clinically useful information in the improvement of current rate control therapies, which are mainly focused on controlling ventricular rate without paying much attention to the atrial fibrillatory process.     

The AV synchrogram: A novel approach to quantify atrioventricular coupling during atrial arrhythmias

The generation of ventricular response during atrial arrhythmias and its dependence on atrial activity is poorly understood. This paper introduces the atrioventricular (AV) synchrogram, a novel method for the beat-to-beat assessment of AV coupling during atrial arrhythmias, based on the stroboscopic observation of the ventricular phase at times triggered by atrial activation. The method was applied on a database of 120 atrial electrograms and ECG signals recorded in patients during typical atrial flutter (AFL), rapid atrial flutter (rAFL), and atrial fibrillation (AF). Synchronized epochs of different n:m order were automatically detected in the AV synchrogram and characterized in terms of percentage of significantly coupled beats (p_lb), maximal length of coupling segments (l_max), average conduction ratio (CR). Synchrogram analysis demonstrated that AV coupling and degree of conduction were significantly affected by the rate and regularity of atrial activity. The occurrence and stability of AV coupled epochs was maximal during regular atrial activation in AFL (median (interquartile range) of p_lb = 100 (100–100)%, l_max = 29.0 (28.5–29.4) s), and significantly (p < 0.001) decreased at faster atrial rates in rAFL (p_lb = 74.3 (57.6–100)%, l_max = 7.4 (3.9–28.7) s). A further decrease of coupling indexes occurred at higher irregularity of atrial activity in AF (p_lb = 25.7 (19.9–30.2)%, l_max = 2.1 (1.8–2.6) s). The increase of atrial rate led to a significant (p < 0.001) reduction of CRs from 0.50 (0.29–0.50) in AFL to 0.25 (0.22–0.25) in rAFL and 0.30 (0.24–0.35) in AF. Application of the analysis to the time course of AF showed the presence of a Farey sequence structure in n:m coupling patterns at increasing atrial rate, which was consistent with the scaling effect of nodal recovery on atrial beats. In conclusion, AV synchrogram analysis enables beat-to-beat assessment of AV coupling and dynamical tracking of AV response during atrial arrhythmias, which may favor mechanistic insight about the genesis of ventricular rhythms and potentially the development of efficacious rate control strategies.     

New-onset atrial fibrillation in sepsis is associated with increased morbidity and mortality

BackgroundThe development of new-onset atrial fibrillation in sepsis has been associated with adverse outcomes.MethodsA systematic literature search was conducted to retrieve articles that investigated the association of new-onset atrial fibrillation in patients diagnosed with sepsis. The primary outcome of interest was the pooled risk ratio (RR) of in-hospital mortality in patients with new-onset atrial fibrillation and sepsis.ResultsSix studies included 3100 patients with new-onset atrial fibrillation in sepsis and 36,900 patients without new-onset atrial fibrillation in sepsis. The pooled RR for in-hospital mortality was 1.45 (95 % CI 1.32–1.60, p < 0.00001, I^2 =24 %). New-onset atrial fibrillation was also associated with increased ICU mortality, ICU and in-hospital length of stay and stroke. New-onset atrial fibrillation occurred more in the elderly, those with a prior history of cardiovascular and respiratory disease, and those with increased severity of illness.ConclusionProspective randomised trials are needed to clarify the significance of new-onset atrial fibrillation in sepsis, optimal treatment strategies for these patients, and the benefit of systemic anticoagulation. Physicians should be aware that new-onset atrial fibrillation in sepsis is not merely an observed temporary arrhythmia but a marker of poor prognosis and should be managed accordingly.     

Ultrastructure of secretion in the atrial gland of a mollusc (Aplysia)

Extracts of the atrial gland of the sea hare Aplysia californiea (Mollusca) induce egg laying when injected into mature individuals. Since egg laying is controlled endogenously by a peptide secreted by neuroendocrine cells in the central nervous system, the relationship between the atrial gland and these central neurons has become an issue of interest. With the particular objective of examining secretory structures we undertook an ultrastructural study of the atrial gland and adjacent tissues. This study revealed that the atrial gland epithelium is composed of two major cell types: ‘goblet-like’ exocrine cells containing large electron-dense granules, and ciliated ‘capping cells’. A non-secretory, and possibly post-secretory, cell containing electron-lucent granules was noted. A region of the large hermaphroditic duct contiguous to the atrial gland, known as the red hemiduct, also displayed capping cells and secretory cells with large granules. The content of these granules is organized into crista-like condensations. The cell also contains iron-rich pigment inclusions.     

A conserved role for FGF signaling in chordate otic/atrial placode formation

The widely held view that neurogenic placodes are vertebrate novelties has been challenged by morphological and molecular data from tunicates suggesting that placodes predate the vertebrate divergence. Here, we examine requirements for the development of the tunicate atrial siphon primordium, thought to share homology with the vertebrate otic placode. In vertebrates, FGF signaling is required for otic placode induction and for later events following placode invagination, including elaboration and patterning of the inner ear. We show that results from perturbation of the FGF pathway in the ascidian Ciona support a similar role for this pathway: inhibition with MEK or Fgfr inhibitor at tailbud stages in Ciona results in a larva which fails to form atrial placodes; inhibition during metamorphosis disrupts development of the atrial siphon and gill slits, structures which form where invaginated atrial siphon ectoderm apposes pharyngeal endoderm. We show that laser ablation of atrial primordium ectoderm also results in a failure to form gill slits in the underlying endoderm. Our data suggest interactions required for formation of the atrial siphon and highlight the role of atrial ectoderm during gill slit morphogenesis.     

Retrieving hidden atrial repolarization waves from standard surface ECGs

Background

This study estimates atrial repolarization activities (Ta waves), which are typically hidden most of the time from body surface electrocardiography when diagnosing cardiovascular diseases. The morphology of Ta waves has been proven to be an important marker for the early sign of inferior injury, such as acute atrial infarction, or arrhythmia, such as atrial fibrillation. However, Ta waves are usually unseen except during conduction system malfunction, such as long QT interval or atrioventricular block. Therefore, justifying heart diseases based on atrial repolarization becomes impossible in sinus rhythm.

Methods

We obtain TMPs in the atrial part of the myocardium which reflects the correct excitation sequence starting from the atrium to the end of the apex.

Results

The resulting TMP shows the hidden atrial part of ECG waves.

Conclusions

This extraction makes many diseases, such as acute atrial infarction or arrhythmia, become easily diagnosed.

     

Effect of flecainide on atrial fibrillatory rate in a large animal model with induced atrial fibrillation

Background

Atrial fibrillatory cycle length has been considered one of the indices of atrial electrical remodelling during atrial fibrillation (AF), which can be assessed from surface ECG by computer-assisted calculation of atrial fibrillatory rate (AFR). Horses have been suggested as a bona fide model for AF studies since horses too, develop lone AF, however data on AF characteristics in horses are extremely sparse and non-invasive characterization of AF complexity using surface ECG processing has not been reported.

Aim

The aim was to study characteristics of induced AF and its modification by flecainide.

Methods

The study group consisted on 3 horses with spontaneous persistent AF and 13 with pace-induced AF. Seven horses were treated with saline (control) and eight with flecainide (2 mg/kg). ECGs were analysed using spatiotemporal cancellation of QRST complexes and calculation of AFR from the residual atrial signal.

Results

At AF onset, AFR was 295?±?52 fibrillations per minute (fpm) in the horses with induced AF treated with flecainide, 269?±?36 fpm in the control group (ns), and 364?±?26 fpm in the horses with spontaneous persistent AF (P?<?0.05 compared to the control group). Flecainide caused a decrease in AFR in all animals and restored sinus rhythm in the animals with induced AF. In the control animals, AFR increased from 269?±?36 fpm to a plateau of 313?±?14 fpm before decreasing to 288?±?28 fpm during the last 10% of the AF episodes preceding spontaneous conversion (P?<?0.05).

Conclusion

AFR in horses with induced AF resembles AFR in humans with paroxysmal AF. Flecainide caused a rapid decrease in AFR in all horses, further supporting the method to be a non-invasive technique to study the effect of antiarrhythmic compounds.

     

Pulmonary vein isolation of symptomatic refractory paroxysmal and persistent atrial fibrillation

Aim. To investigate long-term outcome and to determine predictors of successful pulmonary vein isolation (PVI) in patients with symptomatic paroxysmal or persistent atrial fibrillation (AF) who are refractory or intolerant to antiarrhythmic drugs. Background. The treatment of AF has traditionally been pharmacological aimed at rate or rhythm control. However, rhythm control remains difficult to establish. PVI is reported to be effective in selected patient groups. Methods. Ninety-nine consecutive patients with a mean age of 54±10 years who had paroxysmal or persistent AF were treated in the University Medical Center Groningen. All patients underwent PVI by the same electrophysiologist. Successful PVI was defined as absence of AF on Holter or electrocardiogram (ECG), and no symptoms of AF. Results. After six months of follow-up, 60 (61%) patients were free of AF episodes, both on 96-hour Holter monitoring and on ECGs, and had no symptoms related to AF. Thirty-nine of these 60 patients (65%) were no longer treated with any class I or III antiarrhythmic drugs. Independent determinants of successful PVI were paroxysmal AF (OR 18 [3.5–93], p=0.001), and left pulmonary vein ablation time >55 minutes (OR 15 [2.7–81], p=0.002). Left atrial (parasternal view 42±6 vs. 40±5 mm, p<0.05 and apical view 61±9 vs. 58±8 mm, p<0.05) and right atrial (59±7 vs. 56±5 mm, p<0.05) sizes decreased significantly in the successfully treated patients after six months of follow-up. Conclusion. Independent determinants of a successful outcome after PVI are paroxysmal AF and a longer left atrial ablation time. (Neth Heart J 2009;17:366–72.)     

Alteration of environmental salinity modulates atrial natriuretic peptide concentrations in the gills of the oyster,Crassostrea virginica

Because gills are frequently important in ion transport and osmoregulation, the present investigation was designed to determine if atrial natriuretic peptides (putative osmoregulatory peptides) are present within the gills of a representative euryhaline osmoconforming invertebrate. Utilizing three radioimmunoassays devised to amino acids 1–30, 31–67, and 99–126 of the 126 amino acid prohormone, the gills of 72 eastern oysters, Crassostrea virginica were examined and each found to contain atrial natriuretic peptides, whose content was approximately one-seventh of that within the heart of the oyster. In high salinity (32 parts per thousand, ppt) the content of atrial natriuretic peptides recognized by each of the three radioimmunoassays was lower at 3 days (P < 0.005) and then became higher (P < 0.001) compared with their content in medium salinity (21 and/or 27 ppt). The content of atrial natriuretic peptides within gills in a low salinity environment (8 ppt) was significantly lower (P < 0.05) at 3, 7, and 14 days compared with their content in either medium or high salinity environments. We conclude that atrial natriuretic peptides are present within the gill tissues of Crassostrea virginica and that their content changes with alterations in environmental salinity. Their lower content at 3 days in high salinity implies a release of stored natriuretic-like peptides that are re-synthesized by 1 week. The decreased content of atrial natriuretic peptides at 3 days, 1 and 2 weeks in low salinity versus medium or high salinity environments suggests that their synthesis is decreased when exposed to a lower salinity in the environment.     

Initial experience with AcQMap catheter for treatment of persistent atrial fibrillation and atypical atrial flutter

IntroductionThe AcQMap High Resolution Imaging and Mapping System was recently introduced. This system provides 3D maps of electrical activation across an ultrasound-acquired atrial surface.MethodsWe evaluated the feasibility and the acute and short-term efficacy and safety of this novel system for ablation of persistent atrial fibrillation (AF) and atypical atrial flutter.ResultsA total of 21 consecutive patients (age (mean ± standard deviation) 62 ± 8 years, 23% female) underwent catheter ablation with the use of the AcQMap System. Fourteen patients (67%) were treated for persistent AF and 7 patients (33%) for atypical atrial flutter. Eighteen patients (86%) had undergone at least one prior ablation procedure. Acute success, defined as sinus rhythm without the ability to provoke the clinical arrhythmia, was achieved in 17 patients (81%). At 12 months, 4 patients treated for persistent AF (29%) and 4 patients treated for atypical flutter (57%) remained in sinus rhythm. Complications included hemiparesis, for which intra-arterial thrombolysis was given with subsequent good clinical outcome (n = 1), and complete atrioventricular block, for which a permanent pacemaker was implanted (n = 2). No major complications attributable to the mapping system occurred.ConclusionThe AcQMap System is able to provide fast, high-resolution activation maps of persistent AF and atypical atrial flutter. Despite a high acute success rate, the recurrence rate of persistent AF was relatively high. This may be due to the selection of the patients with therapy-resistant arrhythmias and limited experience in the optimal use of this mapping system that is still under development.Supplementary InformationThe online version of this article (10.1007/s12471-021-01636-w) contains supplementary material, which is available to authorized users.     

Identification of an endogenous glutamatergic transmitter system controlling excitability and conductivity of atrial cardiomyocytes

As an excitatory transmitter system, the glutamatergic transmitter system controls excitability and conductivity of neurons. Since both cardiomyocytes and neurons are excitable cells, we hypothesized that cardiomyocytes may also be regulated by a similar system. Here, we have demonstrated that atrial cardiomyocytes have an intrinsic glutamatergic transmitter system, which regulates the generation and propagation of action potentials. First, there are abundant vesicles containing glutamate beneath the plasma membrane of rat atrial cardiomyocytes. Second, rat atrial cardiomyocytes express key elements of the glutamatergic transmitter system, such as the glutamate metabolic enzyme, ionotropic glutamate receptors (iGluRs), and glutamate transporters. Third, iGluR agonists evoke iGluR-gated currents and decrease the threshold of electrical excitability in rat atrial cardiomyocytes. Fourth, iGluR antagonists strikingly attenuate the conduction velocity of electrical impulses in rat atrial myocardium both in vitro and in vivo. Knockdown of GRIA3 or GRIN1, two highly expressed iGluR subtypes in atria, drastically decreased the excitatory firing rate and slowed down the electrical conduction velocity in cultured human induced pluripotent stem cell (iPSC)-derived atrial cardiomyocyte monolayers. Finally, iGluR antagonists effectively prevent and terminate atrial fibrillation in a rat isolated heart model. In addition, the key elements of the glutamatergic transmitter system are also present and show electrophysiological functions in human atrial cardiomyocytes. In conclusion, our data reveal an intrinsic glutamatergic transmitter system directly modulating excitability and conductivity of atrial cardiomyocytes through controlling iGluR-gated currents. Manipulation of this system may open potential new avenues for therapeutic intervention of cardiac arrhythmias.Subject terms: Cell biology, Molecular biology     

Nkx genes regulate heart tube extension and exert differential effects on ventricular and atrial cell number

Heart formation is a complex morphogenetic process, and perturbations in cardiac morphogenesis lead to congenital heart disease. NKX2-5 is a key causative gene associated with cardiac birth defects, presumably because of its essential roles during the early steps of cardiogenesis. Previous studies in model organisms implicate NKX2-5 homologs in numerous processes, including cardiac progenitor specification, progenitor proliferation, and chamber morphogenesis. By inhibiting function of the zebrafish NKX2-5 homologs, nkx2.5 and nkx2.7, we show that nkx genes are essential to establish the original dimensions of the linear heart tube. The nkx-deficient heart tube fails to elongate normally: its ventricular portion is atypically short and wide, and its atrial portion is disorganized and sprawling. This atrial phenotype is associated with a surplus of atrial cardiomyocytes, whereas ventricular cell number is normal at this stage. However, ventricular cell number is decreased in nkx-deficient embryos later in development, when cardiac chambers are emerging. Thus, we conclude that nkx genes regulate heart tube extension and exert differential effects on ventricular and atrial cell number. Our data suggest that morphogenetic errors could originate during early stages of heart tube assembly in patients with NKX2-5 mutations.     

Left atrial size and risk for all-cause mortality and ischemic stroke

Background:

Limited data are available on the relation between left atrial size and outcome among patients referred for clinically indicated echocardiograms. Our aim was to assess the association of left atrial size with all-cause mortality and ischemic stroke in a large cohort of patients referred for echocardiography.

Methods:

Left atrial diameter was measured in 52 639 patients aged 18 years or older (mean age 61.8 [standard deviation (SD) 16.3] years; 52.9% men) who underwent a first transthoracic echocardiogram for clinical reasons at our institution between April 1990 and March 2008. The outcomes were all-cause mortality and nonfatal ischemic stroke.

Results:

Based on the criteria of the American Society of Echocardiography, 50.4% of the patients had no left atrial enlargement, whereas 24.5% had mild, 13.3% had moderate and 11.7% had severe left atrial enlargement. Over a mean follow-up period of 5.5 (SD 4.1) years, 12 527 patients died, and 2314 patients had a nonfatal ischemic stroke. Cumulative 10-year survival was 73.7% among patients with normal left atrial size, 62.5% among those with mild enlargement, 54.8% among those with moderate enlargement and 45% among those with severe enlargement (p < 0.001). After adjustment in multivariable Cox proportional hazard analysis, left atrial diameter remained a predictor of all-cause mortality in both sexes (hazard ratio [HR] per 1-cm increment in left atrial size 1.17, 95% confidence interval [CI] 1.12–1.22, p < 0.001 in women, and HR 1.09, 95% CI 1.05–1.13, p < 0.001 in men) and of ischemic stroke in women (HR 1.25, 95% CI 1.14–1.37, p < 0.001).

Interpretation:

Left atrial diameter has a graded and independent association with all-cause mortality in both sexes and with ischemic stroke in women.The left atrium plays a major role in cardiac physiology by collecting blood during systole and modulating left ventricular filling during diastole.¹ Left ventricular diastolic dysfunction or mitral valve disease may lead to left atrial pressure or volume overload which, if chronically maintained, may result in left atrial remodeling and enlargement.² As a marker of left ventricular diastolic dysfunction³ or increased filling volumes, left atrial size may provide important prognostic information. In this regard, left atrial enlargement has been related to higher risk of atrial fibrillation^4–7 and cardiovascular events.^8–13 Our aim was to assess the association of left atrial size with all-cause mortality and ischemic stroke in a large cohort of patients referred for echocardiography.     

Clinical application of pacemakers in atrial tachyarrhythmias

The diagnostic programmes of modern pacemakers have increased our knowledge of atrial tachyarrhythmias (ATAs) in chronically paced patients. These programmes also support the evaluation of the effects of pharmacological treatment of ATAs. The success of interruption and/or prevention of ATAs with pacemakers depends strongly on the diagnostic accuracy and the properties of the pacing algorithms, their individual programming and the site and configuration of the pacing leads. Atrial septum pacing can be beneficial in patients with paroxysmal atrial fibrillation and prolonged P wave duration. Recent large-scale studies on preventive and interruptive atrial pacing of ATAs show modestly positive or no results. Therefore, atrial pacing therapy for ATAs should be considered cautiously, serving as an adjuvant to pharmacological treatment rather than as a primary intervention. This also applies for pacing interventions for ATAs in cardiac resynchronisation therapy. The pacemaker algorithms for the detection of ATAs and atrial lead configuration are crucial for the success of pacemaker-mediated prevention or interruption of ATAs. The success of these interventions is dependant on future improvements of pacemaker technology. (Neth Heart J 2008;16 (suppl 1): S20-S24.)     

Neutral endopeptidase inhibitor suppresses the early phase of atrial electrical remodeling in a canine rapid atrial pacing model

Introduction

We examined the acute effects of neutral endopeptidase inhibitor on the hemodynamics and electrical properties of dogs subjected to rapid atrial pacing.

Methods

Ten beagle dogs were used and divided into two groups with and without candoxatril, a neutral endopeptidase inhibitor preadministration. Before and after the 6 hours rapid atrial pacing from the right atrial appendage, the hemodynamics, atrial effective refractory period, and monophasic action potential duration of the right atrial appendage were measured and blood samples were collected. Atrial tissue was also excised after the experiment.

Results

Candoxatril significantly increased plasma ANP levels (Control: 88.4 ± 50.25 vs. Candoxatril: 197.1 ± 32.09 pg/ml, p = 0.004) and prevented reductions in atrial effective refractory period and monophasic action potential duration. We further demonstrated that the treated animals exhibited significantly higher levels of atrial tissue cyclic GMP (Control: 28.1 ± 1.60 fmol/mg vs. Candoxatril: 44.5 ± 12.28 fmol/mg, p = 0.034) as well as that of plasma cyclic GMP (Control: 32 ± 5.5 vs. Candoxatril: 42 ± 7.1 pg/ml, p = 0.028).

Conclusion

Candoxatril suppressed the shortening of atrial effective refractory period and monophasic action potential duration in the rapid atrial pacing model. As plasma ANP and the atrial tissue levels of cyclic GMP were higher in the Candoxatril group than the control, this effect was considered to appear through the reduction of calcium overload caused by ANP and cyclic GMP.