Nodal Conduction Research Articles

Acute effects of simvastatin to terminate fast reentrant tachycardia through increasing wavelength of atrioventricular nodal reentrant tachycardia circuit.

Simvastatin (SV) leads to reduction of ventricular rhythm during atrial fibrillation on rabbit atrioventricular (AV) nodes. The aim of our study was (i) to determine the frequency-dependent effects of SV in a functional model, and (ii) to assess the effects of SV to suppress experimental AV nodal reentrant tachycardia (AVNRT). Selective stimulation protocols were used with two different pacing protocols, His to atrial, and atrial to atrial (AA). An experimental AVNRT model with various cycle lengths was created in three groups of perfused rabbit AV nodal preparations (n=24) including: SV 3μm, SV 7μm, and verapamil 0.1μm. SV increased nodal conduction time and refractoriness by AA pacing. Different simulated models of slow/fast and fast/slow reentry were induced. SV caused inhibitory effects on the slow anterograde conduction (origin of refractoriness) more than on the fast anterograde conduction time, leading to an increase of tachycardia cycle length, tachycardia wavelength and termination of slow/fast reentrant tachyarrhythmia. Verapamil significantly suppressed the basic and frequency-dependent intrinsic nodal properties. In addition, SV decreased the incidence of gap and echo beats. The present study showed that SV in a concentration and rate-dependent manner increased the AV effective refractory period and reentrant tachycardia wavelength that lead to slowing or termination of experimental fast AVNRT. The direction-dependent inhibitory effect of SV on the anterograde and retrograde dual pathways explains its specific antireentrant actions.

GW25-e1417 The feasibility study on the biventricular pacing both dynamic combined of atrioventricular nodal conduction to improve the treatment of heart failure

GW25-e1417 The feasibility study on the biventricular pacing both dynamic combined of atrioventricular nodal conduction to improve the treatment of heart failure

Genome-wide association study of electrocardiographic parameters identifies a new association for PR interval and confirms previously reported associations.

Previous reports have described several associations of PR, QRS, QT and heart rate with genomic variations by genome-wide association studies (GWASs). In the present study, we examined the association of ∼2.5 million SNPs from 2994 Japanese healthy volunteers obtained from the JPDSC database with electrocardiographic parameters. We confirmed associations of PR interval, QRS duration and QT interval in individuals of Japanese ancestry with 11 of the 45 SNPs (6 of 20 for QT, 5 of 19 for PR and 0 of 6 for QRS) observed among individuals of European, African and Asian (Indian and Korean) ancestries. Those results indicate that many of the electrocardiographic associations with genes are shared by different ethnic groups including Japanese. Possible novel associations found in this study were validated by Korean data. As a result, we identified a novel association of SNP rs4952632[G] (maps near SLC8A1, sodium-calcium exchanger) (P = 7.595 × 10(-6)) with PR interval in Japanese individuals, and replication testing among Koreans confirmed the association of the same SNP with prolonged PR interval. Meta-analysis of the Japanese and Korean datasets demonstrated highly significant associations of SNP rs4952632[G] with a 2.325-ms (95% CI, 1.693-2.957 ms) longer PR interval per minor allele copy (P = 5.598 × 10(-13)). Cell-type-specific SLC8A1 knockout mice have demonstrated a regulatory role of sodium-calcium exchanger in automaticity and conduction in sinoatrial node, atrium and atrioventricular node. Our findings support a functional role of sodium-calcium exchanger in human atrial and atrioventricular nodal conduction as suggested by genetically modified mouse models.

Measurement of the ventriculoatrial interval from the coronary sinus during para-Hisian pacing may fail to distinguish ventriculoatrial nodal conduction from conduction over a septal accessory pathway

BackgroundPara-Hisian pacing (PHP) helps differentiate retrograde conduction over an accessory pathway (AP) from retrograde conduction over the atrioventricular (AV) node. This study examined a potential limitation of this technique, focusing on the measurement of the ventriculoatrial (V–A) interval from the coronary sinus (CS) during PHP. MethodsOur subjects were 9 patients undergoing electrophysiological studies before successful catheter ablation of a posteroseptal AP. During PHP, retrograde conduction occurred over an AP when the pacing stimulus to atrium (S–A) interval recorded near the AP remained unchanged whether the His bundle (HB) was captured or not (pattern 1), or when a loss of HB capture was associated with an increase in the S–A interval and no change in the V–A interval near the AP (pattern 2). ResultsPatterns 1 and 2 were observed in 5 (56%) and 2 (22%) patients, respectively. However, in the remaining 2 patients (22%), loss of HB capture during PHP was associated with an increase in the S–A interval (as in pattern 2), whereas the V–A interval near the AP could not be measured because no ventricular electrogram was visible on the CS recording (pattern 3); therefore, the presence of AP could not be confirmed by PHP. In patterns 2 and 3, the atrial activation sequence remained unchanged whether the HB was captured or not. ConclusionsPHP may not be able to discriminate between a retrograde septal AP and AV nodal conduction in patients whose proximal CS recording shows no visible ventricular electrogram.

Blackout during meals: A case report of swallow syncope due to sinus arrest

A 79-year-old male, with a history of percutaneous coronary intervention (PCI), was referred to our cardiovascular department for a detailed examination of blackout caused by sinus arrest only during meals. Ultrasound echocardiography showed normal cardiac contraction with no asynergy, irrespective of the remaining stenotic coronary lesion. An electrophysiological study revealed deteriorated atrioventricular nodal conduction at a Wenckebach point of 70 beats per minute. However, sinus node function was normal as demonstrated by a sinus node recovery time of 1369ms. Coronary angiography showed triple-vessel disease including the remaining stenotic coronary lesion, and a PCI was performed on the right coronary artery. Nevertheless, sinus arrest during meals was unchanged. Swallow syncope was partially improved by dietary modification; however, pacemaker implantation (PMI) was performed eventually, and the patient became asymptomatic after PMI.<Learning objective: Swallow syncope is a rare cause of syncope that belongs to the neurally mediated reflex syncopal syndromes, which can induce a variety of bradyarrhythmias: sinus bradycardia, sinus arrest, sinoatrial block, atrioventricular block, or atrial and ventricular asystole. In this case, we demonstrated that dietary modification or pacemaker implantation improved swallow syncope due to sinus arrest.>

Parahisian pacing: technique, utility, and pitfalls

Several observations and maneuvers in the electrophysiology (EP) laboratory are employed to identify whether retrograde ventriculoatrial conduction is via the atrioventricular (AV) node or an accessory pathway. Parahisian pacing is a unique maneuver where there is no change in the position of the catheter, the position of the stimulating electrode, nor the cycle length for pacing, but rather the pacing output is varied. The primary value for parahisian pacing is to distinguish between a septal accessory pathway and AV nodal conduction. However, more nuanced but just as reliable interpretation is possible to also help identify free-wall accessory pathways, intermittently conducting pathways, multiple accessory pathways, and various combinations of pathway and AV nodal retrograde conduction. In this review, we discuss the importance of correct technique and explain with examples some uncommon, yet instructive, findings when performing parahisian pacing.

Reply to the Editor—XXXX

We thank Prof Anderson and Prof Moorman for their Letter to the Editor referencing our editorial commentary and the opportunity to clarify the sense and context for citing one of their recent reviews in our editorial commentary. 1 Christoffels V.M. Moorman A.F. Development of the cardiac conduction system: why are some regions of the heart more arrhythmogenic than others?. Circ Arrhythm Electrophysiol. 2009; 2: 195-207 Crossref PubMed Scopus (123) Google Scholar , 2 Sylva M. van den Hoff M.J.B. Moorman A.F. Development of the human heart. Am J Med Genet A. 2013; (XX:XX) PubMed Google Scholar , 3 Misiri J. Asirvatham S.J. Can we isolate the pulmonary veins?. Heart Rhythm. 2014; 11: 557-558 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar We agree completely that when stringent criteria for recognition of histologically specialized tissues are used, there is no evidence of nodal tissue or conduction tissue remnants in the left atrial myocardium or pulmonary vein ostium. Letters To The EditorHeart RhythmVol. 11Issue 9PreviewWe read with interest the Editorial Commentary by Misiri and Asirvatham.1 We are surprised, however, that these commentators should cite 2 recent reviews authored by one of us2,3 as evidence in their support. Both the reviews emphasized the fact that the myocardial walls of the left atrium do not contain remnants of the conduction system. Indeed, one review contained an entire paragraph stressing that “pulmonary venous myocardium differs from systemic venous myocardium.” It is true that previous authors have suggested that the pulmonary venous sleeves contain “nodal cardiomyocytes,”4 but we are unaware of molecular or immunocytochemical evidence supporting this notion. Full-Text PDF

Upregulation of adenosine A1 receptors facilitates sinoatrial node dysfunction in chronic canine heart failure by exacerbating nodal conduction abnormalities revealed by novel dual-sided intramural optical mapping.

Although sinoatrial node (SAN) dysfunction is a hallmark of human heart failure (HF), the underlying mechanisms remain poorly understood. We aimed to examine the role of adenosine in SAN dysfunction and tachy-brady arrhythmias in chronic HF. We applied multiple approaches to characterize SAN structure, SAN function, and adenosine A1 receptor expression in control (n=17) and 4-month tachypacing-induced chronic HF (n=18) dogs. Novel intramural optical mapping of coronary-perfused right atrial preparations revealed that adenosine (10 μmol/L) markedly prolonged postpacing SAN conduction time in HF by 206 ± 99 milliseconds (versus 66 ± 21 milliseconds in controls; P=0.02). Adenosine induced SAN intranodal conduction block or microreentry in 6 of 8 dogs with HF versus 0 of 7 controls (P=0.007). Adenosine-induced SAN conduction abnormalities and automaticity depression caused postpacing atrial pauses in HF versus control dogs (17.1 ± 28.9 versus 1.5 ± 1.3 seconds; P<0.001). Furthermore, 10 μmol/L adenosine shortened atrial repolarization and led to pacing-induced atrial fibrillation in 6 of 7 HF versus 0 of 7 control dogs (P=0.002). Adenosine-induced SAN dysfunction and atrial fibrillation were abolished or prevented by adenosine A1 receptor antagonists (50 μmol/L theophylline/1 μmol/L 8-cyclopentyl-1,3-dipropylxanthine). Adenosine A1 receptor protein expression was significantly upregulated during HF in the SAN (by 47 ± 19%) and surrounding atrial myocardium (by 90 ± 40%). Interstitial fibrosis was significantly increased within the SAN in HF versus control dogs (38 ± 4% versus 23 ± 4%; P<0.001). In chronic HF, adenosine A1 receptor upregulation in SAN pacemaker and atrial cardiomyocytes may increase cardiac sensitivity to adenosine. This effect may exacerbate conduction abnormalities in the structurally impaired SAN, leading to SAN dysfunction, and potentiate atrial repolarization shortening, thereby facilitating atrial fibrillation. Atrial fibrillation may further depress SAN function and lead to tachy-brady arrhythmias in HF.

A young patient with atypical type-B Wolff–Parkinson–White syndrome accompanied by left ventricular dysfunction

A 15-year-old asymptomatic male patient presented with an electrocardiographic abnormality and left ventricular (LV) dysfunction (left ventricle ejection fraction of 40%) in a physical examination performed 2 years previously. LV dysfunction did not improve despite optimal medical therapy for dilated cardiomyopathy. Twelve-lead electrocardiography revealed a normal PR interval (138ms) with a small delta-like wave in V2, but not a typical diagnostic wave that could be diagnosed as Wolff–Parkinson–White (WPW) syndrome by an electrocardiogram auto-analysis. Transthoracic echocardiography showed a remarkable asynchronous septal motion. An electrophysiological study was performed to exclude WPW syndrome. An accessory pathway (AP) was revealed on the lateral wall of the right ventricle, and radiofrequency catheter ablation was successfully performed to disconnect the AP. Thereafter, the dyssynchrony disappeared, and LV function improved. The intrinsic atrioventricular nodal conduction was very slow (A-H, 237ms). The results of electrocardiogram auto-analysis could not be used to confirm the diagnosis of WPW syndrome because of the atypical delta wave. Conduction via the right lateral AP caused electrical dyssynchrony in the LV. This case suggests that atypical delta waves should be evaluated without depending on electrocardiographic auto-analyses in patients with LV dysfunction accompanied by dyssynchrony.

Ethanol Infusion in the Vein of Marshall Leads to Parasympathetic Denervation of the Human Left Atrium: Implications for Atrial Fibrillation

This study sought to determine whether ethanol infusion in the vein of Marshall (VOM) can ablate intrinsic cardiac nerves (ICN). ICN cluster around the left atrial epicardium and are implicated in the genesis of atrial fibrillation (AF). Patients undergoing catheter AF ablation underwent adjunctive ethanol injection in the VOM. A multipolar catheter was introduced in the VOM and used for high-frequency stimulation (HFS), either as HFS with P-wave synchronized (SynchHFS), 30 pulses, 100 Hz (n= 8) or as HFS with 3 to 10 s bursts (BurstHFS), 33 Hz (n=72) at 25 mA for 1-ms duration. Atrioventricular (AV) nodal conduction slowing (asystole >2 s or R-R interval prolongation >50%) and AF inducibility were assessed before and after VOM ethanol infusion. Up to 41-ml infusions of 98% ethanol were delivered via an angioplasty balloon in the VOM. SynchHFS induced AF in 8 of 8 patients. In 4 of 8 AF initiated spontaneously without VOM capture. No parasympathetic responses were elicited by SynchHFS. BurstHFS was performed in 32 patients undergoing de novo AF ablation (Group 1)and 40 patients undergoing repeat ablation (Group 2). Parasympathetic responses were found in all 32 Group 1 patients and in 75% of Group 2 patients. After VOM ethanol infusion, parasympathetic responses were abolished in allpatients (both groups). There were no acute complications related to VOM ethanol infusion. The VOM contains ICN that connect with the AV node and can trigger AF. Retrograde ethanol infusion in the VOMreliably eliminates local ICN responses. The VOM is a vascular route for ICN-targeting therapies.

Incidence of and Risk Factors for Catheterization-Induced Complete Heart Block in the Pediatric Cardiac Catheterization Laboratory

The majority of the literature on catheterization-induced heart block (CIHB) was published >30 years ago. The field of cardiac catheterization has evolved, performing more interventional compared with diagnostic cases. We sought to determine the incidence and risk factors of CIHB. A catheterization database that records the occurrence of adverse events on all cases was queried for heart block. Additional retrospective data on event outcome were collected on patients who developed CIHB. Multivariable logistic regression modeling was used to identify risk factors of CIHB (odds ratio, 95% confidence interval). In a 6-year period, 6183 cases were performed. The median weight was 15.0 (7.0-47.0) kg, with 29% consisting of infants <1 year. A total of 72% involved complex congenital heart disease. One hundred thirty-five cases were complicated by CIHB (2.2%; 95% confidence interval, 1.9-2.6). Age <1 year (3.0; 2.2-4.3) and case duration ≥2 hours (3.4; 2.0-6.0) were risk factors of CIHB; cardiac anatomy and intervention performed were not. A total of 96% of CIHB recovered within 1 week but 6 patients underwent pacemaker placement (3 L-loop ventricles, 2 intracardiac devices, 1 double inlet-double outlet RV). Of these, 50% recovered atrioventricular nodal conduction within 1 month; 2 patients with L-loop ventricles and 1 patient with a left ventricular-to-right atrial device did not recover. The incidence of CIHB in the pediatric cardiac catheterization laboratory is low at 2.2%. Risk factors include young age and long case duration. The recovery of atrioventricular nodal function after CIHB is high and follows a similar time course to that of postsurgical heart block.

Nonsustained lead noise alert associated with repeating pattern of signals on the ventricular channel: Is there true concern for lead malfunction?

Case summary A 25-year-old woman, relisted for cardiac transplantation, presented with symptoms of syncope and abdominal pain that correlated with periods of complete heart block on monitoring. Her past medical history included congenital Ebstein anomaly, Blalock-Taussig shunt, and eventual orthotropic biatrial cardiac transplant 15 years before the current presentation. She had persistent sinus tachycardia due to failing transplant secondary to allograft vasculopathy. Her ejection fraction was preserved with elevated filling pressures. There was no evidence of rejection on endomyocardial biopsy. Previous electrophysiologic evaluation revealed she had no residual donor-to-recipient atrial conduction, no retrograde ventriculoatrial (VA) conduction, or any other inducible arrhythmia that may have contributed to her functional deterioration. She had dual nodal physiology and conduction down the slow pathway with a long PR interval with heart rates 4120 bpm. She subsequently underwent dual-chamber implantable cardioverter-defibrillator (ICD) placement (St. Jude Medical [SJM] Fortify Assura, St. Paul, MN) for complete heart block associated with syncope. Pacing mode was programmed to DDDR with a base of 80 bpm. Hysteresis rate was set at 60 bpm. Paced atrioventricular (AV) delay was programmed to 225 ms with postventricular atrial refractory period (PVARP) of 275 ms. Lead impedances and sensing and pacing parameters were within normal limits. The alert shown in Figure 1A was received on the Merlin (SJM)

Abstract 18485: Transgenic Expression of a Kir6.1 Gain-of-Function Mutation in the Mouse Heart Results in Av Nodal Conduction Abnormalities

While consensus exists that Kir6.2 gives rise to the pore forming subunit of KATP channels in mouse heart, there is growing evidence that Kir6.1 is also present in mouse cardiomyocytes. Furthermore, Kir6.1 gain-of-function mutation (GOF) is associated with Early Repolarization (ERS) and Brugada Syndromes. It is unclear, however, whether the consequences of the Kir6.1 GOF result from abnormalities in cardiomyocytes, or other cell types in the heart. To assess the consequence of Kir6.1 GOF in cardiomyocytes, we generated Kir6.1[G343D] (GOF) mice under α-myosin heavy chain promoter. Patch-clamp data shows decreased sensitivity to ATP inhibition in GOF myocytes (EC50 = 43.5 ± 6.1 μM in GOF, 8.3 ± 3.1 μM in WT; p = 0.0007), with no significant change in peak current density (WT: 128 ± 23 pA/pF; GOF: 103 ± 24 pA/pF, p = NS). In vivo electrophysiology testing using programmed electrical stimulation (PES) shows slowed sinus cycle length (SCL, ms) (WT:120 ± 8.7; GOF: 134.0 ± 19.7, p = 0.04), and prolonged atrioventricular interval (AVI, ms) for GOF (WT: 38.0 ± 4.3; GOF: 46.7 ± 4.3, p = 0.02). Kir6.1 GOF mice show prolonged atrioventricular effective refractory period (AVERP, ms) (WT: 49.2 ± 6.6; GOF: 65.7 ± 8.4, p = 0.0001) and diminished anterograde AV node conduction, as seen by right atrial (RA) pacing resulting in 1:1 capture (pacing cycle length, ms) (WT: 73.0 ± 8.4, GOF: 85.0 ± 5.0, p = 0.02), Wenckebach (WT: 68.0 ± 8.4; GOF: 79.3 ± 6.1, p = 0.049) and 2:1 capture (WT: 54 ± 4.2; GOF: 63.6 ± 6.3, p = 0.049). However, the Kir6.1 GOF mice did not show any differences in either atrial refractory period (AERP, ms) (WT: 37.5 ± 2.7, GOF: 37.1 ± 10.75, p = NS) or ventricular refractory period (VERP, ms) (WT: 45 ± 9.4, GOF: 44.2 ± 7.36, p = NS). In summary, Kir6.1 GOF mice display significant AV nodal conduction abnormalities, providing a potential model of Kir6.1-dependent ERS.

Evaluation Of Electrocardiogram Parameters In Patients With Breast and Lung Cancer Treated With Chemotherapy and Lipegfilgrastim Or Pegfilgrastim

BackgroundChemotherapy (CTx) may cause adverse events such as neutropenia, febrile neutropenia (FN), and cardiotoxicity. Lipegfilgrastim is a once-per-cycle, fixed-dose, glycoPEGylated granulocyte colony-stimulating factor (G-CSF) being developed to reduce the duration of neutropenia and the incidence of FN in cancer patients receiving CTx. Pegfilgrastim is a long-acting covalent conjugate of recombinant methionyl human G-CSF and monomethoxypolyethylene glycol currently available to decrease infection, as manifested by FN, in cancer patients receiving myelosuppressive anti-cancer drugs. Cardiovascular events have seldom been reported in patients receiving colony-stimulating factors. ObjectiveTo evaluate any possible contributions to the electrocardiogram (ECG) effects of CTx after administration of lipegfilgrastim in lung cancer (vs placebo) and breast cancer (vs pegfilgrastim) patients. MethodsThis analysis is based on 2 phase III studies. Lung cancer patients were given lipegfilgrastim 6 mg (n=248) or placebo (n=125) subcutaneously (SC) once per cycle ∼24 h after CTx (cisplatin, 80 mg/m2/etoposide, 120 mg/m2) for a maximum of 4 cycles. Breast cancer patients were given lipegfilgrastim 6 mg (n=101) or pegfilgrastim 6 mg (n=101) SC once per cycle ∼24 h after CTx (doxorubicin, 60 mg/m2/docetaxel, 75 mg/m2) for a maximum of 4 cycles. ECG analysis was performed on all enrolled patients with ≥1 baseline and 1 on-treatment ECG. Monitoring was performed at baseline (∼24 h before CTx, cycle 1), 24 h after study drug administration in cycles 1 and 4, and at the end-of-study visit. ECG measurements included RR, PR, QRS, and QT intervals; derived variables included QTcF (Fridericia's formula), QTcB (Bazett's formula), and heart rate (HR). Central tendency analysis compared baseline ECG values with those during cycle 1, 4, and at end of study. Outlier analysis determined if there were any patients with exaggerated effects on ECG intervals not revealed by central tendency analysis. Morphologic analyses were performed with regard to ECG waveform. ResultsChanges from baseline placebo-corrected values (lung cancer patients) or baseline (breast cancer patients) for HR, PR and QRS interval duration were not clinically relevant, with no difference between lipegfilgrastim and pegfilgrastim in breast cancer patients. Mean changes from baseline placebo-corrected QTcF interval duration showed no signal effect for lipegfilgrastim on cardiac repolarization in lung cancer patients. Changes in QTcF interval duration between lipegfilgrastim and pegfilgrastim in breast cancer patients were comparable. There were no bradycardic outliers in lung cancer patients treated with lipegfilgrastim and 1 at the end of study in breast cancer patients. In the lung cancer study, there were 4%, 2%, and 4% tachycardic outliers in cycle 1, 4, and end of study, respectively, for patients treated with lipegfilgrastim versus 4%, 0%, and 2% in patients receiving placebo. In the breast cancer study, there were 0%, 4%, and 2% tachycardic outliers in cycle 1, 4, and end of study, respectively, for patients treated with lipegfilgrastim versus 1%, 2%, and 1% in patients treated with pegfilgrastim. There were no outliers for PR interval duration in either study. In the lung cancer study, there were 2%, 1%, and 2% QRS outliers in cycle 1, 4, and end of study, respectively, for lipegfilgrastim-treated patients versus 1%, 0%, and 0% in patients receiving placebo. There was only 1 QRS outlier in the breast cancer study (lipegfilgrastim-treated patient, cycle 1). New morphologic changes from baseline were in ST segment and negative T wave inversions and considered nonspecific. ConclusionsThere was no clear effect of lipegfilgrastim on HR, AV nodal conduction measured by PR interval duration, cardiac depolarization measured by QRS duration, or morphology, and no clear signal of effect on cardiac repolarization in the lung cancer study. In the breast cancer study, treatment with lipegfilgrastim and pegfilgrastim had no effect on ECG parameters except for nonspecific ST-T changes and a comparable increase in QTcF (cardiac repolarization) in the 10-15 ms range. The lack of ECG effect versus placebo in the lung cancer study along with the presence of potential QTcF changes in the breast cancer study suggest that the changes observed in the breast cancer study may be due to causes other than the G-CSF treatment. Disclosures:Lammerich:Merckle/ratiopharm/Teva Pharm Industries: Employment. Müller:Teva Pharmaceuticals, Inc: Employment.

Integrated rate-dependent and dual pathway AV nodal functions: principles and assessment framework

The atrioventricular (AV) node conducts slowly and has a long refractory period. These features sustain the filtering of atrial impulses and hence are often modulated to optimize ventricular rate during supraventricular tachyarrhythmias. The AV node is also the site of a clinically common reentrant arrhythmia. Its function is assessed for a variety of purposes from its responses to a premature protocol (S1S2, test beats introduced at different cycle lengths) repeatedly performed at different basic rates and/or to an incremental pacing protocol (increasingly faster rates). Puzzlingly, resulting data and interpretation differ with protocols as well as with chosen recovery and refractory indexes, and are further complicated by the presence of built-in fast and slow pathways. This problem applies to endocavitary investigations of arrhythmias as well as to many experimental functional studies. This review supports an integrated framework of rate-dependent and dual pathway AV nodal function that can account for these puzzling characteristics. The framework was established from AV nodal responses to S1S2S3 protocols that, compared with standard S1S2 protocols, allow for an orderly quantitative dissociation of the different factors involved in changes in AV nodal conduction and refractory indexes under rate-dependent and dual pathway function. Although largely based on data from experimental studies, the proposed framework may well apply to the human AV node. In conclusion, the rate-dependent and dual pathway properties of the AV node can be integrated within a common functional framework the contribution of which to individual responses can be quantitatively determined with properly designed protocols and analytic tools.

ECG Response: October 15, 2013

HomeCirculationVol. 128, No. 16ECG Response: October 15, 2013 Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBECG Response: October 15, 2013 Originally published15 Oct 2013https://doi.org/10.1161/CIRCULATIONAHA.113.006223Circulation. 2013;128:1795–1796Download figureDownload PowerPointECG Challenge: A 73-year-old man with a history of paroxysmal atrial fibrillation being treated with a β-blocker and digoxin presents to the emergency room after 2 days of nausea, vomiting, and abdominal pain. He is placed on telemetry because of a slightly irregular heart rate. It is thought that he has a viral gastroenteritis. Noted on telemetry are several pauses in the rhythm; hence, a 12-lead ECG is obtained.The rhythm is regular at a rate of 60 bpm, but 2 long RR intervals (of an equivalent duration) are noted with a ventricular rate of 40 bpm (↔). The QRS complex duration is normal (0.08 second), and the QRS complex has a normal morphology. The axis is leftward between −30° and −90° (positive QRS complex in lead I and negative QRS complex in leads II and aVF with an rS morphology). There are two etiologies for an extreme left axis. The first is a chronic inferior wall myocardial infarction in which there is an initial deep Q wave in leads II and aVF; hence the QRS complex has a Qr morphology in these leads. The second is a left anterior fascicular block in which the initial forces are normal; the QRS complex has an rS morphology in leads II and aVF. This is a left anterior fascicular block. The QT/QTc intervals are normal (440/440 milliseconds). There is a P wave before all of the QRS complexes (+) except for the sixth complex (^). The P wave is positive in leads I, II, aVF, and V4 through V6. Hence, there is a normal sinus rhythm. The PR interval is constant (0.48 second) except for the PR interval associated with the seventh QRS complex (↑), which is shorter (0.32 second). Noted after the fifth QRS complex (↓) is an on-time but nonconducted P wave (*). This is followed by a QRS complex after a long pause. The QRS complex has the same morphology as all of the other QRS complexes, but it is not preceded by a P wave; there is a positive waveform at the end of the QRS complex (▾) that is the on-time P wave based on the sinus PP interval (⎵). Hence, there is complete atrioventricular block with an escape junctional complex. There is a P wave (▴) before the seventh QRS complex (↑) with a PR interval that is shorter (0.32 second) than the baseline PR interval (0.48 second). The QRS complex is the same as all of the others. This suggests that this P wave is nonconducted and that the QRS complex is also a junctional escape complex. It has the same RR interval (↔) as the other junctional complex. The presence of escape junctional complexes means that the complete atrioventricular block is the result of an atrioventricular nodal conduction abnormality, which may be attributable to the combined use of a β-blocker and digoxin, both of which impair atrioventricular nodal conduction. Noted is that the junctional QRS complexes have a slightly different amplitude than the sinus QRS complexes. This is often seen with junctional complexes. An explanation for this is that the junctional complex, originating from a focus in the AV junction, enters the bundle of His at a different location compared to a sinus complexes in which the impulse travels through the AV node to enter the bundle of His. As the bundle of His is a series of tracks, the junctional complex is conducted to the ventricle through a slightly different His-Purkinje track. Thus it will have a slightly different amplitude and may also have a slightly different axis compared to a sinus complex.FootnotesCorrespondence to Philip J. Podrid, MD, West Roxbury VA Hospital, Section of Cardiology, 1400 VFW Pkwy, West Roxbury, MA 02132. E-mail [email protected] Previous Back to top Next FiguresReferencesRelatedDetails October 15, 2013Vol 128, Issue 16 Advertisement Article InformationMetrics © 2013 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.113.006223PMID: 24126324 Originally publishedOctober 15, 2013 PDF download Advertisement SubjectsElectrocardiology (ECG)

Differential sequential septal pacing: A simple maneuver to differentiate nodal versus extranodal ventriculoatrial conduction

Distinguishing retrograde nodal conduction from extranodal conduction using an accessory pathway (AP) can sometimes be challenging. To distinguish nodal from extranodal ventriculoatrial (VA) conduction regardless of AP location by proposing a simple method. This method is based on the principle that moving the pacing site progressively from the basal region toward the entrance of the His-Purkinje system should shorten VA time for nodal but not for AP conduction. Sixty-seven patients with supraventricular tachycardia were prospectively recruited. Quadripolar catheters were placed at the right ventricular (RV) apex, right atrium, and His and coronary sinus. The RV septum was sequentially paced at 4 sites: (1) basal, (2) high midventricle, (3) low midventricle, and (4) apex at a cycle length 100 ms shorter than the resting cycle length. The stimulus-to-atrial (SA) interval was measured by using the proximal coronary sinus atrial electrogram. Group 1 (n = 33) had nodal VA conduction; all patients had typical atrioventricular nodal reentrant tachycardia. Group 2 (n = 34) had extranodal VA conduction via an AP: 19 left-sided, 6 right-sided, and 9 posteroseptal. In group 1, the SA interval decreased significantly as pacing site moved closer toward the apex (site 1: 166 ± 35 ms, site 2: 153 ± 32 ms, site 3: 149 ± 32 ms, site 4: 154 ± 33 ms, P < .001, respectively, at sites 2-4 compared with site 1). In contrast, in group 2, the SA interval increased significantly toward the apex (site 1: 149 ± 45 ms, site 2: 158 ± 43 ms, site 3: 161 ± 43 ms, and site 4: 163 ± 40 ms, P < .001, respectively, at sites 2-4 compared with site 1). The SA interval at the high midventricular site (site 2) - SA interval at the base (site 1) ≤ 0 ms for nodal and > 0 ms for extranodal conduction had optimal sensitivity and specificity (nodal: selectivity = 97.0% and specificity = 85.3%; extranodal: selectivity = 85.3% and specificity = 97.0%). Differential sequential pacing of the RV septum reliably distinguishes retrograde atrioventricular nodal conduction from AP conduction.

The funny and not-so-funny effects of dronedarone

The funny and not-so-funny effects of dronedarone

Supraventricular extrasystole due to 1:2 atrioventricular conduction: procedural characteristics and long term follow-up of slow pathway modulation

Background: Dual atrioventricular nodal physiology can cause atrioventricular nodal reentrant tachycardia (ANVRT). However, dual AVN physiology can sometimes also cause atrial extrasystole by 1:2 separate AV conduction via the fast and the slow pathway. This arrhythmia may be treated by radiofrequency modulation of the slow pathway (SPM). So far, only case reports have been published. We here present procedural characteristics and long-term follow-up in a series of five patients who underwent SPM for the treatment of 1:2 AVN conduction. Outcome: A population of 2927 patients who underwent SPM in our institution between 1994 and 2012 was screened for 1:2 AVN conduction. Five patients (2 male; mean age 55±14 yrs) were identified. All patients were highly symptomatic with palpitations. ECG documentation of 1:2 supraventricular extrasystole had been obtained in all patients. During electrophysiological study dual AVN physiology with separate AV nodal conduction via the fast and slow pathway in a 1:2 pattern was revealed in four patients. Mean fast pathway conduction measured as the AH interval was 149±70 ms while mean slow pathway conduction was 536±99 ms. In none of the 5 patients AVNRT was inducible. SPM was performed in all patients with the endpoint of absence of 1:2 conduction, which was tested by programmed atrial stimulation including orciprenaline challenge. In one patient, no dual AVN physiology was inducible despite extensive programmed stimulation and application of chatecholamines. On the ground of typical ECG documentation and severe symptoms, empirical SPM was performed in this case. There were no complications in any of the patients. Long term follow up (69.6±54.8 months) was performed by a telephone questionnaire. 4 patients were free of symptoms. The patient with empirical SPM remained symptomatic; however, he also reported improvement of clinical symptoms due to lower frequency of occurrence and shorter duration of episodes. Conclusion: 1:2 AVN conduction is a rhythm disorder that can be highly symptomatic. Although rare, this diagnosis should be considered in patients with palpitations and ECG documentation compatible with 1:2 AV conduction. Our data show that in this clinical setting catheter ablation is an effective and safe therapy with good long term outcome.

Slow pathway ablation for typical atrioventricular nodal re-entrant tachycardia significantly alters the autonomic modulation of atrioventricular conduction

Atrioventricular (AV) conduction turbulence, biphasic dromotropic response of AV node to single ventricular premature contraction (VPC), consists of early shortening and later prolongation of AV conduction intervals due to the direct electrophysiological mechanisms and perturbation in autonomic modulation. We investigated the acute effect of radiofrequency catheter ablation of slow pathway on AV turbulence. The electrophysiological study was performed in 18 patients (7 men, mean age 49±15years) undergoing catheter ablation for AV nodal reentrant tachycardia. The stimulation protocol consisting of series of isolated VPC (coupling interval of 273±23ms) delivered from right ventricle apex during constant atrial pacing at 100bpm was performed immediately prior to and 8±4min after successful slow-pathway ablation. Averaged post-VPCs profiles of AV conduction intervals were analyzed by purpose-written software. The descriptors of AV turbulence, turbulence onset (TOAV), turbulence slope (TSAV), and AV recovery (R AV) were assessed. Slow-pathway ablation suppressed the AV nodal responsiveness to VPC as evidenced by significant reduction of AV turbulence indices: TOAV: -6.4±7.5% vs. -4.3±6.1% (p<0.05); TSAV: 2.0±2.6ms/RRi vs. 1.0±0.7ms/RRi (p<0.05); and R AV: -13.8±7.3% vs. -6.5±12.7% (p<0.05). Slow-pathway ablation significantly attenuated both vagal and non-autonomic modulation of AV nodal conduction. This effect is likely due to direct thermal injury of AV node associated with the change of properties of AV nodal fast-pathway although specific alteration of peri-AV nodal ganglionated plexi or their neural inputs into the AV node cannot be excluded.