Atrioventricular Conduction Time Research Articles

Unmasking latent preexcitation of a right-sided accessory pathway with intravenous adenosine after unexplained sudden cardiac arrest.

Intravenous adenosine is a simple test that can uncover latent preexcitation via an accessory pathway and is useful in the diagnostic workup of sudden cardiac arrest survivors without an identifiable cause. Latent preexcitation is usually associated with left free wall pathways but may also occur in right-sided accessory pathways with slow antegrade conduction. Although intermittent ECG evidence of preexcitation is generally considered a marker of low risk for sudden death, if this is due to an accessory pathway with long atrioventricular conduction time and short effective refractory period (rather than true intermittent conduction via the pathway), the risk for sudden death may be equal to those accessory pathways with manifest preexcitation.

862Syncav with multipoint pacing improves acute left ventricular hemodynamics

Abstract Funding Acknowledgements Abbott Introduction SyncAV has been shown to improve electrical synchronization by automatically adjusting atrioventricular delay (AVD) according to the intrinsic atrioventricular conduction time. Additional incremental electrical synchronization may be gained by the addition of second left ventricular (LV) pulse with MultiPoint Pacing (MPP). While the electrical synchronization benefits of SyncAV have been previously explored, there has been no assessment of the acute hemodynamic impact of SyncAV with or without MPP. Objective Evaluate the acute LV hemodynamic impact of SyncAV with and without MPP. Methods Heart failure patients with LBBB and QRS duration (QRSd) > 140 ms undergoing CRT-P/D implant with a quadripolar LV lead were enrolled in this prospective study. A guidewire or catheter with pressure transducer was placed in the LV chamber and the maximum pressure change (dP/dtmax) was recorded during the following pacing modes: intrinsic conduction, conventional biventricular pacing with SyncAV (BiV + SyncAV), and MPP with SyncAV (MPP + SyncAV). Twelve-lead surface ECG was used to determine the patient-tailored SyncAV offset that minimized QRSd. Results Twenty-seven patients (67% male, 44% ischemic, 30 ± 7% ejection fraction) completed the acute recordings. Relative to the intrinsic QRSd of 163 ms, BiV + SyncAV reduced QRSd by 21.5% to 124 ms (p < 0.001 vs. intrinsic) and MPP + SyncAV reduced QRSd by 26.6% to 120 ms (p < 0.05 vs. BiV + SyncAV). Beyond electrical synchronization, SyncAV significantly improved acute hemodynamics. Relative to the intrinsic dP/dtmax of 842 mmHg/s, BiV + SyncAV elevated dP/dtmax by 6.3% to 900 mmHg/s (p < 0.001 vs. intrinsic) and MPP + SyncAV elevated dP/dtmax by 8.8% to 926 mmHg/s (p < 0.005 vs. BiV + SyncAV). Despite both QRSd and dP/dtmax improvement with SyncAV and MPP, correlation between electrical and hemodynamic measurements was poor (R2 = 0.0 for BiV + SyncAV, R2 = 0.1 for MPP + SyncAV). Conclusion SyncAV may significantly improve acute LV hemodynamics in addition to electrical synchrony in LBBB patients. Further incremental improvement was achieved by combining SyncAV with MPP. Abstract Figure.

Assessing Dynamic Atrioventricular Conduction Time to RR-interval Coupling in Athletes and Sedentary Subjects.

ResumoFundamento O tempo de condução atrioventricular (TCAV) é influenciado pelo estímulo autonômico e sujeito a remodelação fisiológica.Objetivo Avaliar a variabilidade da TCAV batimento-a-batimento e o intervalo RR em atletas e indivíduos sedentários saudáveis.Métodos Vinte adultos, incluindo 10 indivíduos sedentários saudáveis (controles) e 10 corredores de elite de longa distância (atletas), com idade, peso e altura ajustados foram submetidos à avaliação do equivalente metabólico máximo (MET) e registro de ECG em repouso supino de 15 minutos sete dias depois. O intervalo entre os picos da onda P e da onda R definiu o TCAV. Foram calculadas a média (M) e o desvio padrão (DP) de intervalos RR consecutivos (RR) e TCAV acoplados, bem como as linhas de regressão de RR vs. TCAV (RR-TCAV). A condução AV concordante foi definida como o slope RR-AVCT positivo e, caso contrário, discordante. Um modelo de regressão linear multivariada foi desenvolvido para explicar o MET com base nos parâmetros de variabilidade do TCAV e intervalo RR. Nível de significância: 5%.Resultados Nos atletas, os valores de M-RR e DP-RR foram maiores que nos controles, enquanto M-TCAV e DP-TCAV não foram. Os slopes RR-TCAV foram, respectivamente, 0,038 ± 0,022 e 0,0034 ± 0,017 (p < 0,05). Utilizando um valor de corte de 0,0044 (AUC 0,92 ± 0,07; p < 0,001), o slope RR-TCAV mostrou 100% de especificidade e 80% de sensibilidade. Em um modelo multivariado, o slope DP-RR e RR-TCAV foram variáveis explicativas independentes do MET (razão F: 17,2; p < 0,001), apresentando especificidade de 100% e sensibilidade de 90% (AUC: 0,99 ± 0,02; p < 0,001).Conclusão Em corredores de elite, o acoplamento dinâmico de TCAV para intervalo RR apresenta condução AV discordante espontânea, caracterizada por slope na linha de regressão TCAV negativa vs. intervalo RR. O desvio padrão dos intervalos RR e o slope da linha de regressão do TCAV vs. intervalo RR são variáveis explicativas independentes do MET. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

No increased extracellular volume fraction or conduction time after childhood septal myectomy.

The aim of this study was to assess the effect of surgical septal myectomy performed during early childhood for severe, drug-refractory hypertrophic cardiomyopathy with left ventricular outflow tract obstruction on the extent of septal myocardial extracellular volume fraction and the potential risk of developing atrioventricular cardiac conduction system disease. In this retrospective study, data from 30 patients with a confirmed diagnosis of childhood-onset hypertrophic cardiomyopathy were reviewed including cardiovascular magnetic resonance (CMR) with myocardial T1 mapping and late gadolinium enhancement, histopathology of myocardial specimens, transthoracic echocardiography, electrocardiography, 24-h Holter and cardiopulmonary exercise testing. Eighteen patients without were compared to 12 patients with prior septal myectomy performed during childhood (non-operated versus myectomy patients). Late gadolinium enhancement on CMR as a correlate for focal myocardial fibrosis was found in 53% of patients, predominantly located in the septal region, with no difference between groups. As compared to non-operated patients, those after myectomy showed a similar amount of total and septal extracellular volume fraction, as calculated from pre- and post-contrast CMR T1 mapping, which is a correlate for diffuse interstitial myocardial fibrosis. PQ-intervals or the occurrence of higher degree conduction system disease were equal between the 2 groups. Data from CMR and electrocardiography suggest that surgical septal myectomy performed during early childhood for severe obstructive hypertrophic cardiomyopathy does not cause an increased septal extracellular volume fraction or delayed atrioventricular conduction time on long-term follow-up.

Transcatheter Aortic Valve Implantation and Complications Regarding Cardiac Conductance

Degenerative aortic stenosis is an inflammatory process, affecting up to 12% of patients aged over 85 years. Transcatheter aortic valve implantation (TAVI) has become the preferred option for symptomatic, high and intermediate risk patients, including those denied for surgical valve replacement. Aortic stenosis is associated with prolonged atrio-ventricular (AV) conduction time, as well as higher degree of AV conduction disorders. In addition, it was observed that TAVI patients have a higher incidence of conduction abnormalities during the procedure, as well as during the following days, many of them requiring the implantation of a permanent pacemaker. Definitive guidelines for management of the conduction disorders are not yet available, the burden of choosing the best approach being put on each individual clinician.

Atrial Flutter as the First Manifestation of Progressive Cardiac Conduction Disease in a Young Apparently Healthy Patient: А Case Report

Abstract We reported a case of a twenty-one-year-old man with an atrial flutter as the first manifestation of progressive cardiac conduction disease. The patient was admitted to the cardiology department due to complaints of shortness of breath and a decrease in exercise tolerance, which had happened after physical exercises (running). During ambulatory ECG monitoring persistent AFL was observed with atrial rate 262-297 bpm and ventricular rate 26-136 bpm (average 56 bpm). AV conduction was very variable – 4:1-14:1. The results of ambulatory ECG monitoring during the whole period of recording indicated signs of atrioventricular conduction disturbances. After cardioversion sinus rhythm was restored additional rhythm and conduction disorders were revealed. Ambulatory ECG monitoring was performed two weeks after the initial one, and throughout this recording were registered sinus rhythm on the background of first-degree AV block; transient Mobitz I AV block; and type 2 second-degree sinoatrial block. Trans-esophageal electrophysiology study was performed. During pharmacological denervation of the heart, signs of slowing of the atrioventricular conduction and sinus node recovery time persisted. These changes along with right bundle branch block were regarded as a progressive cardiac conduction disease with an apparently hereditary cause.

Differential effects of sevoflurane and propofol on swine cardiac conduction system

ObjectiveTo compare the effects of sevoflurane and propofol on the porcine cardiac conduction system. Study designA prospective, comparative study of electrophysiological properties of anaesthetics agents in an experimental porcine model. AnimalsA total of 36 hybrid Landrace-Large White pigs. MethodsAfter premedication with 20 mg kg−1 of intramuscular ketamine, anaesthesia was induced with 4.5 mg kg−1propofol intravenously. In 18 consecutive animals, anaesthesia was maintained with propofol (13 mg kg−1 hour−1) and in the remaining 18 animals with 2.66% sevoflurane. The femoral artery and vein were canalized for invasive monitoring, analytical blood gas sampling and intracardiac catheter insertion. Following instrumentation and after a period of stabilization, a customary electrophysiological evaluation was performed. We compared the electrophysiology of the sinus and atrioventricular node (AV) node under sevoflurane or propofol anaesthesia, and the effects of both anaesthetics on atrial and ventricular refractoriness. ResultsThere was a significant difference in sinus node recovery time between sevoflurane and propofol (907 ± 231 versus 753 ± 146 ms, p = 0.02). Sevoflurane in comparison with propofol significantly prolonged specialized AV conduction times, represented by an increased Wenckebach cycle length (272 ± 54 versus 235 ± 40 ms, p = 0.03) and AV nodal refractoriness (327 ± 34 versus 287 ± 30 ms, p = 0.002). In addition, sevoflurane prolonged ventricular refractoriness (298 ± 27 versus 255 ± 38 ms, p = 0.007) and the QT corrected interval (0.50 ± 0.05 versus 0.46 ± 0.09 ms, p = 0.005). Conclusions and clinical relevanceSevoflurane in comparison with propofol, depresses several parameters of sinus and AV nodal function and prolongs the ventricular refractoriness of the porcine cardiac conduction system. These findings should be taken into consideration for the choice of anaesthetic agents in clinical and experimental settings.

Dual atrioventricular nodal pathways: physiology, arrhythmic findings, and electrocardiographic manifestations

The atrioventricular (AV) node is an anatomically well-defined structure, conveniently housed in the triangle of Koch. There are two distinct atrial impulse approaches to the AV node, one of which (in the anterior portion of triangle of Koch) has a faster conduction, while the other one (in the posterior portion) has a slower conduction. However, it is not said that such a conductive duality translates into any arrhythmic phenomena. Actually, these arrhythmias are due to an imbalance of the two pathways electrophysiological properties, which does not always exist. In the presence of such an imbalance, the dual AV nodal physiology is, however, the substrate for various arrhythmias and curious electrocardiographic behaviors. Often the fast pathway is characterized by a relatively long refractory period. In contrast, the slow approach is often characterized by shorter refractoriness.The unbalanced refractoriness of the two nodal pathways constitutes the prerequisite for the most common form of paroxysmal supraventricular tachycardia: the AV nodal reentrant tachycardia (AVNRT). In subjects prone to this type of arrhythmia, during sinus rhythm, nodal conduction usually occurs from the anterior approach (fast pathway). However, a premature atrial beat may find this pathway refractory and cross the AV node through the posterior approach (slow pathway), resulting in a sudden prolongation of the AV conduction time ("jump"). This allows the impulse, once it reaches the common end, to excitate the fast pathway in a retrograde direction and to return backwards to the atrium, thus triggering a circus movement that can result in a "slow-fast" AVNRT. More rarely, an AVNRT can take place in an opposite direction of the reentrant impulse ("fast-slow" variety of AVNRT). A paroxysmal supraventricular tachycardia may seldom occur with a regularly alternating RR cycle, if the reentrant mechanism involves retrogradely an accessory AV pathway and, in anterograde direction, a fast and a slow AV nodal pathway, alternately. Among the mechanisms underlying the total RR irregularity during atrial fibrillation, there is probably also the possibility that the AV node may offer to the atrial impulses two distinct pathways to reach the His bundle. Not too rarely, a dual AV nodal physiology can occur during sinus rhythm, through unexpected and sudden changes in the AV conduction time, so that two distinct PR families can be observed. It is likely that the presence of dual AV nodal pathways can facilitate or promote a Wenckebach conduction mechanism at nodal site.

Antimalarial agents against both sexual and asexual parasites stages: structure-activity relationships and biological studies of the Malaria Box compound 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine (MMV019918) and analogues

Therapies addressing multiple stages of Plasmodium falciparum life cycle are highly desirable for implementing malaria elimination strategies. MMV019918 (1, 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine) was selected from the MMV Malaria Box for its dual activity against both asexual stages and gametocytes. In-depth structure-activity relationship studies and cytotoxicity evaluation led to the selection of 25 for further biological investigation. The potential transmission blocking activity of 25 versus P. falciparum was confirmed through the standard membrane-feeding assay. Both 1 and 25 significantly prolonged atrioventricular conduction time in Langendorff-isolated rat hearts, and showed inhibitory activity of Ba2+ current through Cav1.2 channels. An in silico target-fishing study suggested the enzyme phosphoethanolamine methyltransferase (PfPMT) as a potential target. However, compound activity against PfPMT did not track with the antiplasmodial activity, suggesting the latter activity relies on a different molecular target. Nevertheless, 25 showed interesting activity against PfPMT, which could be an important starting point for the identification of more potent inhibitors active against both sexual and asexual stages of the parasite.

MC225, a Novel Probe for P-glycoprotein PET Imaging at the Blood-brain Barrier: In Vitro Cardiovascular Safety Evaluation.

The P-glycoprotein (P-gp) substrate MC225, at concentrations ≤10 nM, is a valuable radiotracer for positron emission tomography imaging of P-gp function in rats and mice. The aim of this study was to evaluate its potential toxic hazard toward the cardiovascular system through an in-depth analysis of its effects on rat aorta rings, on CaV1.2 channel current (ICa1.2) of A7r5 cells and on Langendorff-perfused rat heart. In aortic rings, MC225 relaxed phenylephrine-induced contraction in a concentration-dependent and endothelium-independent manner, with an IC50 value of about 1 μM. At concentrations ≥3 μM, it antagonized the response to cumulative concentrations of K. MC225, 1 and 10 μM, inhibited ICa1.2 by 15% and 31%, respectively, without affecting either current activation or inactivation kinetics. In Langendorff-perfused rat hearts, only 10 μM MC225 significantly decreased left ventricular pressure and increased coronary perfusion pressure while reducing heart rate and prolonging the cardiac cycle length as well as the atrioventricular conduction time (PQ interval) on the electrocardiogram. Lower concentrations of the drug were ineffective. These findings demonstrate that MC225-induced cardiovascular effects took place at concentrations that are at least 2 orders of magnitude higher than those allowing in vivo measurement of P-gp function. Therefore, MC225 represents a promising positron emission tomography tool for in vivo straightforward P-gp quantification.

Pacsin 2 is required for the maintenance of a normal cardiac function in the developing mouse heart

The Pacsin proteins (Pacsin 1, 2 and 3) play an important role in intracellular trafficking and thereby signal transduction in many cells types. This study was designed to examine the role of Pacsin 2 in cardiac development and function. We investigated the development and electrophysiological properties of Pacsin 2 knockout (P2KO) hearts and single cardiomyocytes isolated from 11.5 and 15.5days old fetal mice. Immunofluorescence experiments confirmed the lack of Pacsin 2 protein expression in P2KO cardiac myocytes in comparison to wildtype (WT). Western blotting demonstrates low expression levels of connexin 43 and T-box 3 proteins in P2KO compared to wildtype (WT). Electrophysiology measurements including online Multi-Electrode Array (MEA) based field potential (FP) recordings on isolated whole heart of P2KO mice showed a prolonged AV-conduction time. Patch clamp measurements of P2KO cardiomyocytes revealed differences in action potential (AP) parameters and decreased pacemaker funny channel (If), as well as L-type Ca2+ channel (ICaL), and sodium channel (INa). These findings demonstrate that Pacsin 2 is necessary for cardiac development and function in mouse embryos, which will enhance our knowledge to better understand the genesis of cardiovascular diseases.

Long-term predictors of stroke in healthy middle-aged men.

Background There are few data on risk factors for stroke during long-term follow-up of healthy individuals. Aims We aimed to investigate the long-term predictive impact on stroke risk of baseline variables including hemodynamic variables measured at rest and during exercise in middle-aged, healthy men. Methods We performed a prospective cohort study of 2014 healthy Norwegian men aged 40-59 years, recruited during the period 1972-1975 and followed until 2007. Participants underwent a comprehensive clinical assessment at baseline, including a bicycle exercise test. Data on stroke, transient ischemic attack, and death were collected on all participants from follow-up visits, medical records, and the National Cause of Death Registry. We used Cox regression for analysis and estimated hazard ratios with 95% confidence intervals, adjusting for traditional risk factors and hemodynamic variables measured at rest and during exercise. Results During 35 years' follow-up, 316 participants (16%) had stroke, of which 287 (91%) were ischemic and 29 (9%) were hemorrhagic. Age (hazard ratio 2.70 per increase in one standard deviation, 95% confidence interval 2.13-3.43), resting systolic blood pressure (hazard ratio 1.24, 95% confidence interval 1.11-1.39), body mass index (hazard ratio 1.14, 95% confidence interval 1.02-1.29), and atrioventricular conduction time (hazard ratio 1.11, 95% confidence interval 1.03-1.19) were significantly associated with long-term risk of stroke, as were maximal systolic blood pressure and heart rate during exercise (hazard ratio 1.28, 95% confidence interval 1.13-1.46, and hazard ratio 0.86, 95% confidence interval 0.74-0.99, respectively). Conclusions Hemodynamic variables at rest and during exercise testing add to the predictive value of clinical variables in healthy, middle-aged men, and should be included in the assessment of long-term risk of stroke, when available.

The effect of atrial pacing site on electrophysiological properties of the atrioventricular junction and induction of atrioventricular nodal reentry in patients with typical atrioventricular nodal reentrant tachycardia.

Clinical studies in humans have shown the site of atrial stimulation to influence atrioventricular (AV) conduction times and refractory periods, the demonstration of dual AV nodal (AVN) pathways, and induction of AVN reentry. These studies often found conflicting results. Moreover, among enrolled patients a minority of them were found to have AVN reentrant tachycardia (AVNRT). The purpose of this study was to investigate the effect of right and left atrial pacing on the electrophysiological properties of the AV junction in the typical AVNRT population. Ninety-two consecutive patients with typical AVNRT were included. Atrial pacing was performed from the high right atrium (HRA) and the left atrium via the proximal coronary sinus (CS). Stimulation from either the HRA or the CS could result in dual AVN physiology and AVNRT. No site-dependent differences in the ease of induction of dual AVN pathways with variability of initiation from either site were found. However, AVNRT was easier to induce from the HRA. With CS pacing the leftward but not the rightward AVN approaches were the entry point to the AV node because of significantly shorter AH conduction times compared to HRA pacing. Conduction over the leftward AVN extensions could initiate the tachycardia with significantly shorter critical AH interval compared to conduction over the rightward AVN extensions; however, the AH interval during AVNRT and its cycle length were not significantly different. Rightward and leftward AVN extensions are regular features of the AV node. Their different electrophysiological properties lead to variation in the demonstration of discontinuous AVN conduction and AVNRT during right and left atrial pacing. Despite the observation that the left AVN extensions could compose the entry point to the reentrant circuit, there is no evidence that they constitute the critical component of sustained typical AVNRT.

Pulmonary hypertension in thyroid diseases.

The influence of thyroid hormones on cardiovascular system is well established. Thyroid diseases can effectively enhance the alteration on cardiovascular system by influencing chronotropic and inotropic actions of the heart; altering the strength and the speed of contraction, the speed of relaxation, the duration of the potential of action, and the duration of the refractory period and atrio-ventricular conduction time; modulating circulation and peripheral vascular beds. One of the more intriguing insights in the connection between thyroid diseases and cardiovascular alterations is related to the evaluation of the influence of thyroid hormones on pulmonary vascular beds. Literature reported several studies regarding the association between both hypothyroidism and hyperthyroidism and the occurrence of increased vascular pulmonary arterial pressure. Nevertheless, the pathogenetic mechanisms able to explain such relationship are not fully understood. Many doubts still persist in the comprehension of the mechanisms of pulmonary hypertension in thyroid diseases. The aim of this review was to provide possible explanation about the possible interaction between pulmonary vascular beds and thyroid function in order to evaluate the possibility of novel perspectives in the general management of patients suffering from thyroid and cardiovascular diseases.

Bachmann's Bundle Pacing not Only Improves Interatrial Conduction but Also Reduces the Need for Ventricular Pacing.

Patients treated for sick sinus syndrome may have interatrial conduction disorder leading to atrial fibrillation. This study was aimed to assess the influence of the atrial pacing site on interatrial and atrioventricular conduction as well as the percentage of ventricular pacing in patients with sick sinus syndrome implanted with atrioventricular pacemaker. The study population: 96 patients (58 females, 38 males) aged 74.1 ± 11.8 years were divided in two groups: Group 1 (n = 44) with right atrial appendage pacing and group 2 (n = 52) with Bachmann's area pacing. We assessed the differences in atrioventricular conduction in sinus rhythm and atrial 60 and 90 bpm pacing, P-wave duration and percentage of ventricular pacing. No differences in baseline P-wave duration in sinus rhythm between the groups (102.4 ± 17 ms vs. 104.1 ± 26 ms, p = ns.) were noted. Atrial pacing 60 bpm resulted in longer P-wave in group 1 vs. group 2 (138.3 ± 21 vs. 106.1 ± 15 ms, p < 0.01). The differences between atrioventricular conduction time during sinus rhythm and atrial pacing at 60 and 90 bpm were significantly longer in patients with right atrial appendage vs. Bachmann's pacing (44.1 ± 17 vs. 9.2 ± 7 ms p < 0.01 and 69.2 ± 31 vs. 21.4 ± 12 ms p < 0.05, respectively). The percentage of ventricular pacing was higher in group 1 (21 vs. 4%, p < 0.01). Bachmann's bundle pacing decreases interatrial and atrioventricular conduction delay. Moreover, the frequency-dependent atrioventricular conduction lengthening is much less pronounced during Bachmann's bundle pacing. Right atrial appendage pacing in sick sinus syndrome patients promotes a higher percentage of ventricular pacing.

Mouse ECG findings in aging, with conduction system affecting drugs and in cardiac pathologies: Development and validation of ECG analysis algorithm in mice.

Mouse models are extremely important in studying cardiac pathologies and related electrophysiology, but very few mouse ECG analysis programs are readily available. Therefore, a mouse ECG analysis algorithm was developed and validated. Surface ECG (lead II) was acquired during transthoracic echocardiography from C57Bl/6J mice under isoflurane anesthesia. The effect of aging was studied in young (2-3months), middle-aged (14months) and old (20-24months) mice. The ECG changes associated with pharmacological interventions and common cardiac pathologies, that is, acute myocardial infarction (AMI) and progressive left ventricular hypertrophy (LVH), were studied. The ECG raw data were analyzed with an in-house ECG analysis program, modified specially for mouse ECG. Aging led to increases in P-wave duration, atrioventricular conduction time (PQ interval), and intraventricular conduction time (QRS complex width), while the R-wave amplitude decreased. In addition, the prevalence of arrhythmias increased during aging. Anticholinergic atropine shortened PQ time, and beta blocker metoprolol and calcium-channel blocker verapamil increased PQ interval and decreased heart rate. The ECG changes after AMI included early JT elevation, development of Q waves, decreased R-wave amplitude, and later changes in JT/T segment. In progressive LVH model, QRS complex width was increased at 2 and especially 4weeks timepoint, and also repolarization abnormalities were seen. Aging, drugs, AMI, and LVH led to similar ECG changes in mice as seen in humans, which could be reliably detected with this new algorithm. The developed method will be very useful for studies on cardiovascular diseases in mice.

Analysis of pacemaker ECGs

The key to a successful analysis of a pacemaker electrocardiogram (ECG) is the application of the systematic approach used for any other ECG without a pacemaker: analysis of (1) basic rhythm and rate, (2) QRS axis, (3) PQ, QRS and QT intervals, (4) morphology of P waves, QRS, ST segments and T(U) waves and (5) the presence of arrhythmias. If only the most obvious abnormality of a pacemaker ECG is considered, wrong conclusions can easily be drawn. If a systematic approach is skipped it may be overlooked that e.g. atrial pacing is ineffective, the left ventricle is paced instead of the right ventricle, pacing competes with intrinsic conduction or that the atrioventricular (AV) conduction time is programmed too long. Apart from this analysis, a pacemaker ECG which is not clear should be checked for the presence of arrhythmias (e.g. atrial fibrillation, atrial flutter, junctional escape rhythm and endless loop tachycardia), pacemaker malfunction (e.g. atrial or ventricular undersensing or oversensing, atrial or ventricular loss of capture) and activity of specific pacing algorithms, such as automatic mode switching, rate adaptation, AV delay modifying algorithms, reaction to premature ventricular contractions (PVC), safety window pacing, hysteresis and noise mode. A systematic analysis of the pacemaker ECG almost always allows a probable diagnosis of arrhythmias and malfunctions to be made, which can be confirmed by pacemaker control and can often be corrected at the touch of the right button to the patient's benefit.

Cardiohemodynamic and electrophysiological effects of a selective EP4 receptor agonist ONO­-AE1­-329 in the halothane-anesthetized dogs

Cardiovascular effects of a highly selective prostaglandin E2 type 4 (EP4) receptor agonist ONO-AE1-329 were assessed with the halothane-anesthetized dogs (n=6). ONO-AE1-329 was intravenously infused in three escalating doses of 0.3, 1 and 3ng/kg/min for 10min with a pause of 20min between the doses. The low dose of 0.3ng/kg/min significantly increased maximum upstroke velocity of left ventricular pressure by 18% at 20min, indicating increase of ventricular contractility. The middle dose of 1ng/kg/min significantly decreased total peripheral resistance by 24% and left ventricular end-diastolic pressure by 32% at 10min, indicating dilation of arteriolar resistance vessels and venous capacitance ones, respectively; and increased cardiac output by 25% at 10min in addition to the change induced by the low dose. The high dose of 3ng/kg/min increased heart rate by 34% at 10min; decreased mean blood pressure by 14% at 10min and atrioventricular nodal conduction time by 13% at 5min; and shortened left ventricular systolic period by 8% at 10min and electromechanical coupling defined as an interval from completion of repolarization to the start of ventricular diastole by 39% at 10min in addition to the changes induced by the middle dose. No significant change was detected in a ventricular repolarization period. These results indicate that ONO-AE1-329 may possess a similar cardiovascular profile to typical phosphodiesterase 3 inhibitors as an inodilator, and suggest that EP4 receptor stimulation can become an alternative strategy for the treatment of congestive heart failure.

Sudden shortening of the paced AV delay: is this normal pacemaker function?

The 200 ms paced AV delay is equal to the native AV conduction time, which leads to the phenomenon called ventricular pseudofusion as the ‘paced QRS’ morphology is identical to the native QRS morphology (QRS complexes marked with an asterisk, Fig. 1) [1]. This is an important observation for two reasons. First, the pacemaker should be reprogrammed to an extended paced AV delay to avoid unnecessary ventricular pacing. Secondly, the presence of ventricular pseudofusion is the clue to answer the question about the short paced AV delay of the third beat. Fig. 1 Postoperative standard 12-lead ECG (1 mV/10 mm, 25 mm/s paper speed). The pseudofusion QRS complexes are marked with an asterisk. See text for details There are various pacemaker features that can shorten the paced AV delay from the set parameter, e.g. ventricular safety pacing [2]. However, in this case, there is no need for knowledge about pacemaker features. If this was a normal pacemaker feature, we should see fully paced QRS morphology when the pacemaker shortens the AV delay to 110 ms (third beat on Fig. 1). The only potential physiological explanation is a junctional ectopy, occurring exactly on time with the ventricular pacing spike, exactly at the time the paced AV delay is shortened, which is extremely unlikely. Therefore, this has to be an artifact. When one examines the printed text above the ECG, the letters are squeezed together right above the part of the tracing with the shortened paced AV delay (rectangular frame in Fig. 1). The ECG machine intermittently stopped rolling the paper for about 90 ms at a time, effectively cutting out 90 ms segments from the ECG tracing. Since the paper had a pre-printed grid, this unusual artifact was not easily detectable.

Molecular Investigation into the Human Atrioventricular Node in Heart Failure

The atrioventricular node (AVN), the molecular basis has been studied in animal models; however, the human AVN remains poorly explored at the molecular level in heart failure patients. We studied ex vivo donor human hearts rejected for transplantation (n=6) and end-stage failing hearts with cardiomyopathy of various etiologies (n=6). Microdissection and quantitative PCR (qPCR) were used to anatomically map mRNA expression in both failing and non-failing hearts from tissue sections through the AVN, atrial and ventricular muscle. In the failing ventricle significant (P<0.05) downregulation is apparent for vimentin, hERG and Kir3.4 and trend to downregulation for Nav1.5, Cav1.2, Tbx3, Kir2.1, NCX1, Cx43 and Cx45. In the failing atrium, there is non-significant trend in upregulation for Nav1.5, HCN2, Cav3.1, Kv1.5, Kir3.1, RYR2 and significant upregulation for Cx40 and trend in downregulation for hERG, Kir2.1 and NCX1, and significant downregulation for HCN4 and Kir3.4. In the failing AVN there is significant (P<0.05) downregulation for vimentin, collagen, Tbx3, Kir3.1, Kir3.4, Cx45 and HCN4; there is also trend toward downregulation for HCN2, Kv1.5, Kir2.1 and RYR2. In the failing AVN there is significant (P<0.05) upregulation for Cx40, HCN1 and Cav3.1; and trend in upregulation for Nav1.5 and Cx43. For several transcripts, we also analysed corresponding protein expression via immunofluorescence. The protein expression data on the AVN for HCN1, Cav3.1 and Cx40 support qPCR data. Remodelling of AVN in heart failure might contribute to prolonged AV conduction time and could explain the prolonged PR interval that occurs in heart failure patients.