Atrioventricular Conduction Time Research Articles

Analysis of cardiohemodynamic and electrophysiological effects of morphine along with its toxicokinetic profile using the halothane-anesthetized dogs.

Although morphine has been used for treatment-resistant dyspnea in end-stage heart failure patients, information on its cardiovascular safety profile remains limited. Morphine was intravenously administered to halothane-anesthetized dogs (n=4) in doses of 0.1, 1 and 10 mg/kg/10 min with 20 min of observation period. The low and middle doses attained therapeutic (0.13 µg/mL) and supratherapeutic (0.97 µg/mL) plasma concentrations, respectively. The low dose hardly altered any of the cardiovascular variables except that the QT interval was prolonged for 10-15 min after its start of infusion. The middle dose reduced the preload and afterload to the left ventricle for 5-15 min, then decreased the left ventricular contractility and mean blood pressure for 10-30 min, and finally suppressed the heart rate for 15-30 min. Moreover, the middle dose gradually but progressively prolonged the atrioventricular conduction time, QT interval/QTcV, ventricular late repolarization period and ventricular effective refractory period without altering the intraventricular conduction time, ventricular early repolarization period or terminal repolarization period. A reverse-frequency-dependent delay of ventricular repolarization was confirmed. The high dose induced cardiohemodynamic collapse mainly due to vasodilation in the initial 2 animals by 1.9 and 3.3 min after its start of infusion, respectively, which needed circulatory support to treat. The high dose was not tested further in the remaining 2 animals. Thus, intravenously administered morphine exerts a rapidly appearing vasodilator action followed by slowly developing cardiosuppressive effects. Morphine can delay the ventricular repolarization possibly through IKr inhibition in vivo, but its potential to develop torsade de pointes will be small.

Abstract 14310: Evaluation of Ventricular Pacing Suppression Algorithmsin Dual Chamber Pacemaker: Results of 'Leader' Study

Introduction: Several algorithms have been proposed to reduce unnecessary right ventricular (RV) pacing, and their operations are based on two different mechanisms: (i) atrioventricular (AV) hysteresis (AVH) and (ii) DDD to AAI pacing mode change. Hypothesis: The purpose of our study was to evaluate the efficacy and safety of two ventricular pacing suppression algorithms: Intrinsic Rhythm Support (IRS) plus algorithm (using AVH, IRSplus) and VP suppression (DDD to AAI mode change) algorithm (VpS). Methods: This was a multicenter, randomized study conducted in 11 tertiary hospitals in South Korea. Patients with sinus node dysfunction and receiving dual-chamber permanent pacemaker implantation were included in this study. After the implantation, patients maintained a fixed AV interval for three months. The AV conduction time was determined as the "atrial pacing to ventricular sensing interval" observed from the marker channel during the PPM implantation was set as the sensed AV delay. The paced AV delay was set to be the sensed AV delay+30ms. Subsequently, patients were randomly assigned to either the VpS or IRSplus algorithm group and were followed for 12 months with assessments every 6 months. Results: A total of 118 patients were enrolled, and the total RV pacing percentage (Vp%) of the patients during the 3 months with a fixed AV interval was 10.9±16.0 on average. They were randomly assigned to VpS and IRSplus groups, with 62 and 56 patients in each group. Six months later, the average Vp% was 14.6±18.8 to 2.7±6.0, P<0.001 and 6.8±10.9 to 1.1±4.0, P<0.001 for the VpS and IRSplus groups, respectively. This trend was maintained for additional 6 months (VpS group: 4.6±9.5; IRSplus group: 1.2±3.8). The effects of algorithms were more pronounced in groups with an intrinsic PR interval of < 200ms, and the IRSplus showed better efficacy (Figure). Conclusions: The two ventricular pacing suppression algorithms were effective in reducing Vp% compared to the fixed AV interval.

Acute osimertinib exposure induces electrocardiac changes by synchronously inhibiting the currents of cardiac ion channels.

Introduction: As the third generation of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), osimertinib has demonstrated more significant cardiotoxicity than previous generations of EGFR-TKIs. Investigating the mechanism of osimertinib cardiotoxicity can provide a reference for a comprehensive understanding of osimertinib-induced cardiotoxicity and the safety of the usage of this drug in clinical practice. Methods: Multichannel electrical mapping with synchronous ECG recording was used to investigate the effects of varying osimertinib concentrations on electrophysiological indicators in isolated Langendorff-perfused hearts of guinea pigs. Additionally, a whole-cell patch clamp was used to detect the impact of osimertinib on the currents of hERG channels transfected into HEK293 cells and the Nav1.5 channel transfected into Chinese hamster ovary cells and acute isolated ventricular myocytes from SD rats. Results: Acute exposure to varying osimertinib concentrations produced prolongation in the PR interval, QT interval, and QRS complex in isolated hearts of guinea pigs. Meanwhile, this exposure could concentration-dependently increase the conduction time in the left atrium, left ventricle, and atrioventricular without affecting the left ventricle conduction velocity. Osimertinib inhibited the hERG channel in a concentration-dependent manner, with an IC50 of 2.21 ± 1.29μM. Osimertinib also inhibited the Nav1.5 channel in a concentration-dependent manner, with IC50 values in the absence of inactivation, 20% inactivation, and 50% inactivation of 15.58 ± 0.83μM, 3.24 ± 0.09μM, and 2.03 ± 0.57μM, respectively. Osimertinib slightly inhibited the currents of L-type Ca2+ channels in a concentration-dependent manner in acutely isolated rat ventricular myocytes. Discussion: Osimertinib could prolong the QT interval; PR interval; QRS complex; left atrium, left ventricle, and atrioventricular conduction time in isolated guinea pig hearts. Furthermore, osimertinib could block the hERG, Nav1.5, and L-type Ca2+ channels in concentration-dependent manners. Therefore, these findings might be the leading cause of the cardiotoxicity effects, such as QT prolongation and decreased left ventricular ejection fraction.

The impact of chronotropic incompetence on atrioventricular conduction times in heart failure patients.

Intrinsic atrioventricular (AV) conduction is used to optimize AV intervals with cardiac resynchronization therapy (CRT) in most device algorithms. Atrial pacing and heart rate affect conduction times, but little is known regarding differeces among chronotropic incompetent(CI) and competent(CC) patients to guide programming. RAVE was a multicenter prospective trial of CRT patients. Heart rate was increased with incremental atrial pacing and with submaximal exercise. According to the maximal heart rate achieved during exercise, patients were classified as either CI or CC. For CI patients, an additional symptom-limited exercise with rate-adaptive pacing activated was performed. Intracardiac intervals were measured from the implantable lead electrograms in multiple postures. There were 12 subjects with CI and 24 with CC. With atrial pacing, AV interval immediately increased and gradually increased with incremental atrial pacing in all patients. However, the changes in the atrial to right ventricular (ARV) and atrial to left ventricular (ALV) intervals with increasing atrial pacing rates were about threefold greater in CI patients compared to CC patients (24.3 ± 28.9 vs. 7.2 ± 5.5ms/10bpm for ARV and 22.7 ± 25.6 vs. 7.1 ± 5.7ms/10bpm for ALV in the standing position, p < 0.05). In CI pacing with rate-adaptive pacing during exercise, AV interval changes with paced heart rate were variable. The AV response to overdrive atrial pacing at rest may provide a simple means of identifying chronotropic competence in CRT patients. For patients with CI, who often require rate-adaptive atrial pacing, rate-adaptive AV algorithms should be adjusted individually.

Effectiveness of the repurposed drug isotretinoin in an experimental murine model of Chagas disease

Benznidazole and nifurtimox are the drugs currently used for the treatment of Chagas disease, however its side effects may affect patient adherence. In the search for new alternative therapies, we previously identified isotretinoin (ISO), an FDA-approved drug widely used for the treatment of severe acne through a drug repurposing strategy. ISO shows a strong activity against Trypanosoma cruzi parasites in the nanomolar range, and its mechanism of action is through the inhibition of T. cruzi polyamine and amino acid transporters from the Amino Acid/Auxin Permeases (AAAP) family. In this work, a murine model of chronic Chagas disease (C57BL/6 J mice), intraperitoneally infected with T. cruzi Nicaragua isolate (DTU TcI), were treated with different oral administrations of ISO: daily doses of 5 mg/kg/day for 30 days and weekly doses of 10 mg/kg during 13 weeks. The efficacy of the treatments was evaluated by monitoring blood parasitemia by qPCR, anti-T. cruzi antibodies by ELISA, and cardiac abnormalities by electrocardiography. No parasites were detected in blood after any of the ISO treatments. The electrocardiographic study of the untreated chronic mice showed a significant decrease in heart rate, while in the treated mice this negative chronotropic effect was not observed. Atrioventricular nodal conduction time in untreated mice was significantly longer than in treated animals. Mice treated even with ISO 10 mg/kg dose every 7 days, showed a significant reduction in anti-T. cruzi IgG levels. In conclusion, the intermittent administration of ISO 10 mg/kg would improve myocardial compromise during the chronic stage.

Dependence of the Atrioventricular Conduction Time on the Conduction through the Atrioventricular Node and His-Purkinje System.

The electrical depolarization of the heart passes through various structures of the cardiac conduction system, which modify its conduction to different extents. In this study, we investigated the relationship between the atrioventricular conduction time (AV interval) and its contributors, the atrioventricular node (AVN) and the His-Purkinje system (HPS), as represented by the AH and HV intervals, respectively. We also compared sex differences in these intervals and their relations. Resting intracardiac tracings lasting 5 min were obtained from 64 patients (33 women) during an invasive electrophysiological study. The aforementioned intervals were measured for all consecutive beats. The mean AH interval was 85.9 ms, HV 43.7 ms, and AV 129.6 ms. Men had longer AH (80.0 vs. 65.9 ms), HV (38.4 vs. 35.3 ms), and AV intervals (124.7 vs. 108.5 ms) than women. The AV intervals were linearly correlated with AH intervals in all patients (r2 = 0.65). No significant correlation was found between AV and HV intervals in all patients (r2 = 0.05). There were no sex differences in these associations. Our results suggest that the atrioventricular conduction time depends mainly on the conduction through the AVN and less on the HPS. These relations are similar in both sexes, although men had longer conduction times through the AVN, HPS, and total atrioventricular conduction time.

Genetic variation rs6795970 of the SCN10A gene is associated with PR interval in young population of Republic of Moldova

Abstract Background/Objectives The electrocardiographic PR interval reflects atrial and atrioventricular nodal conduction time. Prolongation of the PR interval increase risk of atrial fibrillation (AF) and heart block. Genome-wide association studies (GWAS) have identified association of a nonsynonymous single nucleotide polymorphism (SNP), rs6795970, in the SCN10A gene with PR interval in individuals of European and Asian ancestry. The aim of the study was to determine distribution of the genetic variants of rs6795970, associated with PR interval in young population of Republic of Moldova. Methods 1380 young participants from Republic of Moldova aged between 19–25 years, were genotyped for rs6795970 in the SCN10A gene, using TaqMan SNP Genotyping Assay. Results The genotype G/G, A/G, A/A distributions of rs6795970 among participants were 37%, 48%, 15%, respectively (χ2=0.086, p=0.770). The allele frequencies for G and A, in young participants were 61% and 39%, respectively. We observed association between rs6795970_A and a prolongation of the PR interval (p=0.003). Conclusions In our study, we determined that distribution of the genetic variants of rs6795970, associated with PR interval in young population of Republic of Moldova was consistent with 1000 Genomes data in the European population. Therefore, our data demonstrate that the A allele is associated with prolongation of the PR interval and at least 15% of all participants (the A/A genotype), may have an increased risk of conduction abnormalities. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National project “Study of molecular genetic polymorphism of metabolic risk factors in young population of the Republic of Moldova National project “Identification and validation of genetic and epigenetic biomarkers in chronic non-communicable diseases with major impact on public health”

Short-Term Atrioventricular Dysfunction Recovery after Post-TAVI Pacemaker Implantation.

Permanent pacemaker implantation (PPI) represents a frequent complication after transcatheter aortic valve implantation (TAVI) due to atrio-ventricular (AV) node injury. Predictors of early AV function recovery were investigated. We analyzed 50 consecutive patients (82 ± 6 years, 58% males, EuroSCORE: 7.8 ± 3.3%, STS mortality score: 5 ± 2.8%). Pacemaker interrogations within 4–6 weeks from PPI were performed to collect data on AV conduction. The most common indication of PPI was persistent third-degree (44%)/high-degree (20%) AV block/atrial fibrillation (AF) with slow ventricular conduction (16%) after TAVI. At follow-up, 13 patients (26%) recovered AV conduction (i.e., sinus rhythm with stable 1:1 AV conduction/AF with a mean ventricular response >50 bpm, associated with a long-term ventricular pacing percentage < 5%). At multivariate analysis, complete atrio-ventricular block independently predicted pacemaker dependency at follow-up (p = 0.019). Patients with persistent AV dysfunction showed a significant AV conduction time prolongation after TAVI (PR interval from 207 ± 50 to 230 ± 51, p = 0.02; QRS interval from 124 ± 23 to 147 ± 16, p < 0.01) compared to patients with recovery, in whom AV conduction parameters remained unchanged. Several patients receiving PPI after TAVI have recovery of AV conduction within a few weeks. Longer observation periods prior to PPI might be justified, and algorithms to minimize ventricular pacing should be utilized whenever possible.

Atrioventricular Synchronization for Detection of Atrial Fibrillation and Flutter in One to Twelve ECG Leads Using a Dense Neural Network Classifier.

This study investigates the use of atrioventricular (AV) synchronization as an important diagnostic criterion for atrial fibrillation and flutter (AF) using one to twelve ECG leads. Heart rate, lead-specific AV conduction time, and P-/f-wave amplitude were evaluated by three representative ECG metrics (mean value, standard deviation), namely RR-interval (RRi-mean, RRi-std), PQ-interval (PQi-mean, PQI-std), and PQ-amplitude (PQa-mean, PQa-std), in 71,545 standard 12-lead ECG records from the six largest PhysioNet CinC Challenge 2021 databases. Two rhythm classes were considered (AF, non-AF), randomly assigning records into training (70%), validation (20%), and test (10%) datasets. In a grid search of 19, 55, and 83 dense neural network (DenseNet) architectures and five independent training runs, we optimized models for one-lead, six-lead (chest or limb), and twelve-lead input features. Lead-set performance and SHapley Additive exPlanations (SHAP) input feature importance were evaluated on the test set. Optimal DenseNet architectures with the number of neurons in sequential [1st, 2nd, 3rd] hidden layers were assessed for sensitivity and specificity: DenseNet [16,16,0] with primary leads (I or II) had 87.9–88.3 and 90.5–91.5%; DenseNet [32,32,32] with six limb leads had 90.7 and 94.2%; DenseNet [32,32,4] with six chest leads had 92.1 and 93.2%; and DenseNet [128,8,8] with all 12 leads had 91.8 and 95.8%, indicating sensitivity and specificity values, respectively. Mean SHAP values on the entire test set highlighted the importance of RRi-mean (100%), RR-std (84%), and atrial synchronization (40–60%) for the PQa-mean (aVR, I), PQi-std (V2, aVF, II), and PQi-mean (aVL, aVR). Our focus on finding the strongest AV synchronization predictors of AF in 12-lead ECGs would lead to a comprehensive understanding of the decision-making process in advanced neural network classifiers. DenseNet self-learned to rely on a few ECG behavioral characteristics: first, characteristics usually associated with AF conduction such as rapid heart rate, enhanced heart rate variability, and large PQ-interval deviation in V2 and inferior leads (aVF, II); second, characteristics related to a typical P-wave pattern in sinus rhythm, which is best distinguished from AF by the earliest negative P-peak deflection of the right atrium in the lead (aVR) and late positive left atrial deflection in lateral leads (I, aVL). Our results on lead-selection and feature-selection practices for AF detection should be considered for one- to twelve-lead ECG signal processing settings, particularly those measuring heart rate, AV conduction times, and P-/f-wave amplitudes. Performances are limited to the AF diagnostic potential of these three metrics. SHAP value importance can be used in combination with a human expert’s ECG interpretation to change the focus from a broad observation of 12-lead ECG morphology to focusing on the few AV synchronization findings strongly predictive of AF or non-AF arrhythmias. Our results are representative of AV synchronization findings across a broad taxonomy of cardiac arrhythmias in large 12-lead ECG databases.

PO-618-01 IMPACT OF PR INTERVAL PROLONGATION ON THE RISK OF HIGH GRADE CONDUCTIVE DISORDERS AFTER TRANSCATHETER AORTIC VALVE IMPLANTATION

The development of high-grade conductive disorder (HGCD) is one of the most frequent complications after Transcatheter Aortic Valve Implantation (TAVI). Variation in atrioventricular conduction time (PR interval) after TAVI and its specific impact on the risk of permanent pacing implantation (PPI) have been poorly described.

Impact of PR interval prolongation on the risk of high-grade conductive disorders after transcatheter aortic valve implantation

The development of high-grade conduction disturbances is one of the most frequent complications after transcatheter aortic valve implantation (TAVI). Variation in atrioventricular conduction time (PR interval) after TAVI and its specific impact on the risk of permanent pacing implantation (PPI) have been poorly described. The aim of this study was to evaluate the impact of increase in PR interval after TAVI on the incidence of PPI for high-grade conductive disorder. This is a single-center retrospective cohort analysis of 1466 patients undergoing TAVI from January 2010 to December 2018. We excluded patients with prior pacemaker, non-sinus rhythm, TAVI by transapical or transaortic approach and PPI after TAVI for sick sinus syndrome. We observed the variation in PR interval of the electrocardiogram before TAVI (baseline) and at day 1 (D1) of the procedure. The final analysis included 902 patients. Among them, 342 (37.9%) had a previous first-degree atrioventricular block and 13.2% had a new one after TAVI. 207 patients (23.0%) received a PPI for conductive disorders. The mean analysable PR prolongation in 779 patients was 8 ± 26 ms, the risk of developing a high-grade conductive disorder was estimated at 30.6% when PR prolongation was ≥ 40 ms. Multivariable analysis revealed that prolongation of PR interval ≥ 40 ms on D1 was by itself associated with the occurrence of these high-grade conductive disturbances (HR = 4.9 [2.5; 10.0], P < 0.001) more significantly than preexisting right bundle branch block (HR 3.6 [1.7; 7.7], P = 0.001) or de novo left bundle branch block (HR 2.8 [1.5; 5.2], P = 0.001) (Fig. 1). PR interval prolongation greater than or equal to 40 ms at D1 of transcatheter aortic valve implantation is a critical factor to consider in estimating the risk of PPI for high-grade conductive disorder.

216 The ‘inflammatory perfect storm’: a case of COVID-19 pneumonia complicated by pulmonary embolism

AimsThe inflammatory ‘cytokine storm’ that distinguishes COVID-19 pneumonia is associated with a state of systemic hypercoagulability, which leads to thrombotic complications on the venous, arterial, and microvascular side. Indeed, in patients with COVID-19, systemic inflammation, coagulation activation, hypoxemia, and immobilization expose a high risk of pulmonary embolism, which significantly worsens the prognosis of these patients.Methods and resultsIn this report, we discuss the case of a 71-year-old female, with no prior medical history, admitted to the emergency department for syncope, dyspnoea, and fever started 48 h earlier. At presentation, ear temperature was 37 °C, oxygen saturation was 96% on oxygen therapy (6 l/min), the patient appeared hypertensive (160/80 mmHg) and tachycardic (114 b.p.m.). Laboratory tests revealed normal white blood cells count (10 000/μl) and increased C reactive protein (5.60 mg/dl), troponin I (0.417 ng/ml), and d-dimer levels (15743 ng/ml). Electrocardiogram showed sinus tachycardia at HR of 120/min, normal atrioventricular conduction time, new onset right bundle branch block, and inverted T waves on DIII. Considering the symptoms, CTPA was performed, revealing massive acute bilateral pulmonary embolism with peripheral ground glass opacities. Those findings were suggestive of COVID-19 pneumonia. Indeed, the patient was positive for SARS-CoV-2 infection, and a diagnosis of COVID-19 pneumonia complicated by pulmonary embolism was made. Treatments included oxygen, subcutaneous low molecular weight heparin (LWMH), and corticosteroids have been administrated according to current international guidelines. Since no haemodynamic instability was observed during hospitalization the patient was discharged on Warfarin therapy for 6 months.ConclusionsIn COVID-19 patients treated in a hospital the incidence of pulmonary embolism (PE) is very high. Patients with COVID-19 infection have respiratory symptoms, which often may not be distinguishable from pulmonary embolism symptoms. So, unexpected respiratory worsening, signs of right ventricular dysfunction on transthoracic echocardiogram, and ECG changes should lead to suspicion of the co-presence of pulmonary embolism. This case report shows how COVID-19 infection can be strongly associated with thrombotic complications. For this reason, the guidelines recommend anticoagulation at standard prophylactic doses in all patients admitted with COVID-19 infection.

Analysis of Resibufogenin on Cardiac conduction reveals a species difference in the cardiac electrophysiology: Rats versus guinea pigs.

Resibufogenin (RBG) is a chemical ingredient of Chan Su. In our research, we found RBG affected cardiac rhythm in a negative chronotropic way in vivo. The cardiac Mapping system ex vivo and the patch clamp in vitro were used to explore how RBG influenced the cardiac electrophysiological properties. The negative chronotropic action of RBG at 100 μM might be attribute to prolongation in the atrioventricular conduction time and reduction in the ventricular conduction velocity. Using whole-cell patch clamp in ventricular myocytes of adult rats, we found that RBG prolonged the action potential duration (APD) in APD20, APD50, and APD90 at 100 μM and inhibited calcium currents (ICa), total outward potassium currents (IK), and transient outward potassium current (Ito) in a concentration-dependent manner, but not on the inward rectifying potassium current (IK1). Notably, RBG had a potent proarrhythmic action ex vivo in the isolated perfused guinea pig hearts at 10 μM, but not in rats. To avoid the potential cardiotoxicity derived from the distributional differences of ion channels among species, the effect of RGB on IKr in hERG-HEK293 cells was detected. The IC50 of RGB on IKr was more than 100 μM. In summary, all these results indicated that the negative chronotropic action of RBG relied on the blocking activities on multiple ion channels, and the species-difference of proarrhythmic effects might result from lack of the Ito on the myocardial membrane of guinea pigs. Anyhow, the cardiotoxicity observed in guinea pigs required further detailed studies to mitigate the potential risks in the clinical application of Chan Su.

Efficacy of ivabradine in HIV-associated dilated cardiomyopathy.

Ivabradine is a pure heart rate-lowering drug that acts directly on the sinus node and does not affect atrioventricular or intraventricular conduction times, myocardial contractility or ventricular repolarization. Ivabradine is used in the treatment of adults with New York Heart Association (NYHA) class II-IV chronic heart failure (CHF) with systolic dysfunction, in sinus rhythm, with a heart rate of ≥75 beats per minute (bpm). This report describes the beneficial effect of ivabradine on clinical parameters in a HIV-infected patient with dilated cardiomyopathy presenting with NYHA class III CHF symptoms. Ivabradine improved functional capacity and left ventricular (LV) systolic function in our patient with HIV-related dilated cardiomyopathy and CHF. This report also lists the summaries of potential clinically significant interaction, likely to require additional monitoring, alteration of drug dosage or timing of administration, between ivabradine and antiretroviral drugs.

Smoking Accelerates Atrioventricular Conduction in Humans Concordant with Increased Dopamine Release.

Smoking is associated with cardiac arrhythmia, stroke, heart failure, and sudden cardiac arrest, all of which may derive from increased sympathetic influence on cardiac conduction system and altered ventricular repolarization. However, knowledge of the effects of smoking on supraventricular conduction, and the role of the sympathetic nervous system in them, remains incomplete. Participants with intermediate-high cardiovascular disease risk were measured for urinary catecholamines and cotinine, and 12-lead electrocardiograms (ECGs) were measured for atrial and atrioventricular conduction times, including P duration, PR interval, and PR segment (lead II), which were analyzed for associations with cotinine by generalized linear models. Statistical mediation analyses were then used to test whether any significant associations between cotinine and atrioventricular conduction were mediated by catecholamines. ECG endpoints and urinary metabolites were included from a total of 136 participants in sinus rhythm. Atrial and atrioventricular conduction did not significantly differ between smokers (n = 53) and non-smokers (n = 83). Unadjusted and model-adjusted linear regressions revealed cotinine significantly and inversely associated with PR interval and PR segment, but not P duration. Dopamine, norepinephrine, and epinephrine all inversely associated with PR interval, whereas only dopamine was also inversely associated with PR segment (p < 0.05). Dopamine and norepinephrine (but not epinephrine) also associated positively with cotinine. Dopamine mediated the relationship between cotinine and PR interval, as well as the relationship between cotinine and PR segment. Smoking is associated with accelerated atrioventricular conduction and elevated urinary dopamine and norepinephrine. Smoking may accelerate atrioventricular nodal conduction via increased dopamine production.

Cardioprotection by triiodothyronine following caloric restriction via long noncoding RNAs

Severe caloric-restriction compromises thyroid hormone (TH) status, apparently to save energy and proteins for enduring stress stimulus. However, a persistent decrease in TH levels may compromise heart function. We hypothesized that supplementation of low dose active TH or targeting hypoxia-inducible factor-1-alpha, HIF-1α (a strong activator of deiodinase enzyme that degrades peripheral active THs) will prevent deterioration of cardiac performance. Adult mice were subjected to acute fasting based on institutional animal protocols with ad libitum access to water. The following groups were studied: Control mice with free access to food; severe caloric restriction fasting only group; Fasting with Triiodo-l-Thyronine (T3); Fasting with HIF-1α inhibitor (BAY). Cardiac hemodynamic and electrophysiological studies were performed and role of long noncoding RNAs were explored. Following severe caloric-restriction, we found that body weights, and heart weights to a partial extent, were decreased. Low-dose T3 treatment attenuated left ventricular hemodynamic impairment in indices of cardiac contractility and relaxation. In electrophysiology studies, fasting mice developed atrial tachyarrhythmias upon induction. This reverted to control levels following T3 treatment. There was a significant increase in atrioventricular conduction time and significant decrease in heart rate following fasting. Both these changes were attenuated following T3 treatment. Furthermore, BAY partially improved hemodynamics. Compared to the severe caloric-restriction group, both T3 and BAY reduced MALAT1 and GAS5 long noncoding RNA expression. These new findings indicate that T3 and BAY protect from cardiac decompensation secondary to acute severe caloric-restriction partly mediated by long noncoding RNAs.

Irregular orthodromic atrioventricular reentrant tachycardia using the left lateral accessory pathway due to intermittent mitral isthmus block

Mitral isthmus block during left lateral accessory pathway ablation has been reported in the past. Here, we document for the first time an irregular atrioventricular reciprocating tachycardia due to alternating mitral isthmus block and mitral isthmus delay, resulting in different atrioventricular node conduction times and tachycardia cycle length.

Functional modulation of atrio-ventricular conduction by enhanced late sodium current and calcium-dependent mechanisms in Scn5a1798insD/+ mice.

Aims SCN5A mutations are associated with arrhythmia syndromes, including Brugada syndrome, long QT syndrome type 3 (LQT3), and cardiac conduction disease. Long QT syndrome type 3 patients display atrio-ventricular (AV) conduction slowing which may contribute to arrhythmogenesis. We here investigated the as yet unknown underlying mechanisms.Methods and resultsWe assessed electrophysiological and molecular alterations underlying AV-conduction abnormalities in mice carrying the Scn5a1798insD/+ mutation. Langendorff-perfused Scn5a1798insD/+ hearts showed prolonged AV-conduction compared to wild type (WT) without changes in atrial and His-ventricular (HV) conduction. The late sodium current (INa,L) inhibitor ranolazine (RAN) normalized AV-conduction in Scn5a1798insD/+ mice, likely by preventing the mutation-induced increase in intracellular sodium ([Na+]i) and calcium ([Ca2+]i) concentrations. Indeed, further enhancement of [Na+]i and [Ca2+]i by the Na+/K+-ATPase inhibitor ouabain caused excessive increase in AV-conduction time in Scn5a1798insD/+ hearts. Scn5a1798insD/+ mice from the 129P2 strain displayed more severe AV-conduction abnormalities than FVB/N-Scn5a1798insD/+ mice, in line with their larger mutation-induced INa,L. Transverse aortic constriction (TAC) caused excessive prolongation of AV-conduction in FVB/N-Scn5a1798insD/+ mice (while HV-intervals remained unchanged), which was prevented by chronic RAN treatment. Scn5a1798insD/+-TAC hearts showed decreased mRNA levels of conduction genes in the AV-nodal region, but no structural changes in the AV-node or His bundle. In Scn5a1798insD/+-TAC mice deficient for the transcription factor Nfatc2 (effector of the calcium-calcineurin pathway), AV-conduction and conduction gene expression were restored to WT levels.ConclusionsOur findings indicate a detrimental role for enhanced INa,L and consequent calcium dysregulation on AV-conduction in Scn5a1798insD/+ mice, providing evidence for a functional mechanism underlying AV-conduction disturbances secondary to gain-of-function SCN5A mutations.

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) &amp;gt; 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 &amp;lt; 0.001 vs. intrinsic) and MPP + SyncAV reduced QRSd by 26.6% to 120 ms (p &amp;lt; 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 &amp;lt; 0.001 vs. intrinsic) and MPP + SyncAV elevated dP/dtmax by 8.8% to 926 mmHg/s (p &amp;lt; 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.