Sinus Cycle Length Research Articles

Electrophysiological differences of randomized deep sedation with dexmedetomidine versus propofol

BackgroundDexmedetomidine and propofol are common sedatives in intensive care units and for interventional procedures. Both may compromise sinus node function and atrioventricular conduction.The objective of this prospective, randomized study is to compare the effect of dexmedetomidine with propofol on sinus node function and atrioventricular conduction.MethodsIn a tertiary care center in Switzerland we included from September 2019 to October 2020 160 patients (65 ± 11 years old; 32% female) undergoing first ablation for atrial fibrillation by cryoballoon ablation or by radiofrequency ablation.Patients were randomly assigned to deep sedation with dexmedetomidine (DEX group) versus propofol (PRO group). A standard electrophysiological study was performed after pulmonary vein isolation with the patients still deeply sedated and hemodynamically stable.ResultsEighty patients each were randomized to the DEX and PRO group. DEX group patients had higher baseline sinus cycle length (1022 vs. 1138 ms; p = 0.003) and longer sinus node recovery time (SNRT400; 1597 vs. 1412 ms; p = 0.042). However, both corrected SNRT and normalized SNRT did not differ. DEX group patients had longer PR interval (207 vs. 186 ms; p = 0.002) and AH interval (111 vs. 95 ms, p = 0.008), longer Wenckebach cycle length of the atrioventricular node (512 vs. 456 ms; p = 0.005), and longer atrioventricular node effective refractory period (390 vs. 344 ms; p = 0.009). QRS width and HV interval were not different. An arrhythmia, mainly atrial fibrillation, was induced in 33 patients during the electrophysiological study, without differences among groups (20% vs. 15%, p = 0.533).ConclusionsDexmedetomidine has a more pronounced slowing effect on sinus rate and suprahissian AV conduction than propofol, but not on infrahissian AV conduction and ventricular repolarization. These differences need to be taken into account when using these sedatives.Trial registrationClinicalTrials.gov number NCT03844841, 19/02/2019

The influence of subclavian ansae stimulation on cardiac hemodynamics and electrophysiology in atrial fibrillation- exploring a novel target for neuromodulation in atrial fibrillation (SAS-AF study)

Abstract Background Sympathetic nervous system activation plays a significant role in arrhythmia development and maintenance.Neuromodulation techniques such as stellate ganglion block and sympathectomy, are limited by off-target side effects and complex targeting.The Subclavian Ansae (SA,a nerve cord encircling the subclavian artery) may be an intravascular site allowing specific targeting of the cardiac afferent sympathetic system.Preclinical studies have revealed increased sympathetic tone upon selective SA stimulation. Objective We sought to define for the first time in Humans the functional anatomy and physiology of Subclavian Ansae via a percutaneous approach. Methods A prior cadaveric study defined the anatomical course of the subclavian ansae, encircling the subclavian arteries and connecting the middle cervical ganglia to inferior cervical ganglia/stellate.Patients undergoing catheter ablation for paroxysmal atrial fibrillation(pAF) under general anesthesia were prospectively recruited for the study. Subclavian Ansae stimulation (SAS) was performed on the left and/or the right (L/SAS ± R/SAS) within the subclavian artery using the TactiCath Ablation Catheter introduced via a femoral arterial sheath. Stimulation parameters included up to 70 V output, 10 Hz frequency, and pulse width of 2-4ms for 20-30s. Test pulses ensured no cardiac capture during stimulation. Participants discontinued antiarrhythmic agents at least 4-5 half-lives prior to the procedure. Invasive arterial blood pressure(BP), heart rate (HR), and electrophysiological parameters were recorded in response to selective stimulation. An increase of ten percent or more in either arterial blood pressure(BP) or heart rate(HR) from the initial baseline measurements was deemed a positive response. Results 15 patients (62±11 years, 9 males, pAF duration 51±24 months) underwent the simulation protocol prior to their clinical AF ablation procedure. A positive hemodynamic response was observed in nine patients, and among them, arrhythmia was inducible in 3 patients (atrial fibrillation in 2 patients and repeated runs of atrial ectopy in 1 patient) in response to SAS. Mean sinus cycle length(CL) decreased(chronotropic) after stimulation,particularly with a significant change observed in response to R/SAS. Additionally,L/SAS led to a notable increase in mean systolic (SBP) and diastolic(DBP) blood pressure (inotropic). While the mean right atrial effective refractory period (ERP) did not significantly decrease after stimulation, there was a demonstrable difference in interatrial conduction time(dromotropy). Six patients, including the initial 3 subjected to low-energy stimulation (up to 12V), did not exhibit an adrenergic response. Conclusion This study represents the first successful application of selective SAS in humans. A heterogeneity in electrophysiological modulation by SAS exists, including laterality.The SA is a potential important target for targeted autonomic neuromodulation therapy

Cryoballoon cardioneuroablation: New electrophysiological insights

BackgroundCardioneuroablation(CNA) targeting ganglionated plexi has shown promise in treating vasovagal syncope. Only radiofrequency ablation has been used to achieve this goal thus far. ObjectiveWe investigated the utility of cryo-balloon ablation(CBA) of the pulmonary veins as a potential simplified approach to CNA. MethodsWe are reporting our observations of autonomic modulation in a series of 17 patients undergoing CBA for atrial fibrillation and our early experience using CBA of the PVs in 3 patients with malignant vagal syncope. ResultsIn 17 patients undergoing CBA of AF, sinus cycle length was recorded intra-procedurally after ablation of individual PVs. We demonstrated most pronounced shortening of the sinus cycle length after isolation of the right upper PV which was ablated last. There was reduced SNRT and AV nodal ERP after CBA. The elevation in resting heart rate by 6-7 beats/minute following CBA persisted during a follow-up of 12 months. We performed CBA of the PVs in 3 patients with recurrent vagal syncope mediated by sinus arrest (n=2) and AV block (n=1). In all patients, isolation of the right upper PV resulted in marked shortening of sinus cycle length. During a follow-up of 178±43 days (134-219 days) CNA resulted in abolition of pauses, bradycardia related symptoms and syncope in all patients. ConclusionCBA of the PVs (most importantly the right upper PV) may be a predictable anatomic CNA approach in patients with refractory vagal syncope due to sinus arrest and/or AV block and may deserve systematic investigation as a tool to perform CNA.

Abstract 16250: Latent His-Purkinje Disease Unmasked by Beta Blocker Overdose

Background Symptomatic bradycardia usually has a single mechanism and treatment modality. Identifying the culprit mechanism can be challenging, especially when faced with concurrent pathologies. We present a case of severe symptomatic bradycardia where appropriate management of one mechanism unmasked a second mechanism, with a need for pacemaker placement. Case Presentation A 56-year-old patient presented with beta blocker overdose and severe bradycardia. The initial ECG showed sinus bradycardia with a sinus cycle length of 2060ms and 2:1 AV conduction, with each conducted P wave preceded by a long-coupled junctional escape beat. Atropine resulted in shortening of the junctional escape interval but had no effect on the sinus rate. There was now 1:1 AV conduction, with each P wave being preceded by a faster junctional escape beat. Glucagon resulted in acceleration of the sinus rate to a cycle length of ~820ms (73 bpm) with return of 1:1 AV conduction, a PR interval of 200ms, and no junctional beats. Conducted beats showed a right bundle branch block and left axis deviation. The dependence of AV conduction on a preceding QRS complex within a certain window of time highly suggested infranodal conduction disease manifesting as phase 4 AV block. While normal sinus rates and 1:1 AV conduction were restored with glucagon, the presence of infranodal disease warranted dual chamber pacemaker implantation. In follow-up, with atrial pacing support, there was < 1% ventricular pacing. Discussion Two causes of bradycardia were simultaneously present - sinus bradycardia due to beta blocker overdose, and 2nd degree AV block due to His-Purkinje disease. Phase 4 AV block is a mechanism of paroxysmal AV block (PAVB) in patients with diseased His-Purkinje system. Spontaneous depolarization occurs in diseased fibers during prolonged periods of ventricular pause, such as with slowing of the sinus rate. The sodium channels are blocked during phase 4 of the action potential and therefore the conduction system is incapable of depolarizing due to low resting membrane potentials. In this case, AV 1:1 conduction can only be restored with a premature ventricular contraction. This is an overall under-recognized entity and should be managed with pacemaker implantation.

Vasovagal Responses to Human Monomorphic Ventricular Tachycardia: Hemodynamic Implications From Sinus Rate Analysis

BackgroundFactors determining hemodynamic stability during human ventricular tachycardia (VT) are incompletely understood. ObjectivesThe purposes of this study were to characterize sinus rate (SR) responses during monomorphic VT in association with hemodynamic stability and to prospectively assess the effects of vagolytic therapy on VT tolerance. MethodsThis is a retrospective analysis of patients undergoing scar-related VT ablation. Vasovagal responses were evaluated by analyzing sinus cycle length before VT induction and during VT. SR responses were classified into 3 groups: increasing (≥5 beats/min, sympathetic), decreasing (≥5 beats/min, vagal), and unchanged, with the latter 2 categorized as inappropriate SR. In a prospective cohort (n = 30) that exhibited a failure to increase SR, atropine was administered to improve hemodynamic tolerance to VT. ResultsIn 150 patients, 261 VT episodes were analyzed (29% untolerated, 71% tolerated) with median VT duration 1.6 minutes. A total of 52% of VT episodes were associated with a sympathetic response, 31% had unchanged SR, and 17% of VTs exhibited a vagal response. A significantly higher prevalence of inappropriate SR responses was observed during untolerated VT (sustained VT requiring cardioversion within 150 seconds) compared with tolerated VT (84% vs 34%; P < 0.001). Untolerated VT was significantly different between groups: 9% (sympathetic), 82% (vagal), and 32% (unchanged) (P < 0.001). Atropine administration improved hemodynamic tolerance to VT in 70%. ConclusionsNearly one-half of VT episodes are associated with failure to augment SR, indicative of an under-recognized pathophysiological vasovagal response to VT. Inappropriate SR responses were more predictive of hemodynamic instability than VT rate and ejection fraction. Vagolytic therapy may be a novel method to augment blood pressure during VT.

Site-specific effects of dobutamine on cardiac conduction and refractoriness.

Isoproterenol, a non-specific beta agonist, is commonly used during electrophysiology studies (EPS). However, with the significant increase in the price of isoproterenol in 2015 and the increasing number of catheter ablations performed, the cost implications cannot be ignored. Dobutamine is a less expensive synthetic compound developed from isoproterenol with a similar mechanism to enhance cardiac conduction and shorten refractoriness, thus making it a feasible substitute with a lower cost. However, the use of dobutamine for EPS has not been well-reported in the literature. To determine the site-specific effects of various doses of dobutamine on cardiac conduction and refractoriness and assess its safety during EPS. From February 2020 to October 2020, 40 non-consecutive patients scheduled for elective EPS, supraventricular tachycardia, atrial fibrillation, and premature ventricular contraction ablations at a single center were consented and prospectively enrolled to assess the effect of dobutamine on the cardiac conduction system. At the end of each ablation procedure, measures of cardiac conduction and refractoriness were recorded at baseline and with incremental doses of dobutamine at 5, 10, 15, and 20 mcg/kg/min. For the primary analysis, the change per dose of dobutamine from baseline to each dosing level of dobutamine received by the patients, comparing atrioventricular node block cycle length (AVNBCL), ventricular atrial block cycle length (VABCL) and sinus cycle length (SCL), was tested using mixed-effect regression. For the secondary analysis, dobutamine dose level was tested for association with relative changes from baseline of each electrophysiologic parameter (SCL, AVNBCL, VABCL, atrioventricular node effective refractory period (AVNERP), AH, QRS, QT, QTc, atrial effective refractory period (AERP), ventricular effective refractory period (VERP), using mixed-effect regression. Changes in systolic and diastolic blood pressures were also assessed. The Holm-Bonferroni method was used to adjust for multiple testing. For the primary analysis there was no statistically significant change of AVNBCL and VABCL relative to SCL from baseline to each dose level of dobutamine. The SCL, AVNBCL, VABCL, AVNERP, AERP, VERP and the AH, and QT intervals all demonstrated a statistically significant decrease from baseline to at least one dose level with incremental dobutamine dosing. Two patients (5%) developed hypotension during the study and one patient (2.5%) received a vasopressor. Two patients (5%) had induced arrhythmias but otherwise no major adverse events were noted. In this study, there was no statistically significant change of AVNBCL and VABCL relative to SCL from baseline to any dose level of dobutamine. As expected, the AH and QT intervals, and the VABCL, VERP, AERP and AVNERP all significantly decreased from baseline to at least one dose level with an escalation in dobutamine dose. Dobutamine was well-tolerated and safe to use during EPS.

A Minimally Invasive Approach for Cardiac Electrophysiology Studies in Mice

Review A Minimally Invasive Approach for Cardiac Electrophysiology Studies in Mice Min Zi , * , Sabu Abraham , Alicia D'souza , David Hutchings , Sukhpal Prehar , Xin Wang , and Elizabeth J Cartwright Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, United Kingdom * Correspondence: min.zi@manchester.ac.uk Received: 6 January 2023 Accepted: 9 February 2023 Published: 25 March 2023 Abstract: Atrial fibrillation and ventricular tachycardia are commonly seen in clinic. Different approaches have been developed to investigate underlying mechanisms. Transvenous approach (TA) is widely used for studies but has several drawbacks. We therefore developed a novel minimally invasive approach (MIA) for mechanistic studies. Study included 27 male C57BL/6J mice, 19 for MIA and 8 for TA. Under general anaesthesia, ECG was recorded. A key hole was made on the right first intercostal space by separating the intercostal muscles, followed by the exposure of the superior vena cava and the top of the atrium. An EPR-800 catheter was inserted vertically, perpendicular to the chest, for atrial pacing and flatly over the ventricles for ventricular pacing. Burst S1–S1 and decremental S1–S2 pacing protocols were performed to evaluate SA recovery time (SNRT), the atrioventricular node effective refractory period (AVN-ERP), Wenckebach period, ventricular ERP, and arrhythmia susceptibility. MIA was successfully performed in all 19 mice without any complications. One mouse died during TA due to venous rupture. Compared MIA with TA, surgical time were significantly shorter (P&lt;0.0001). Wenckebach period was shorter as well (P&lt;0.05). No difference was found in baseline sinus cycle length, SNRT, correct SNRT, AVN-ERP, ventricular ERP, and arrhythmia susceptibility (all P&gt;0.05). The novel MIA outplays TA by providing similar outcomes of PES but consuming less time, demanding less surgical expertise, and reducing the potential of surgical complications. Given the minimal tissue injury, it also provides great potential as a recovery procedure for longitudinal study.

819 PSEUDO-MOBITZ VAGAL ATRIOVENTRICULAR BLOCK: TWO CASE REPORTS IN YOUNG HEALTHY MEN

Abstract We reported the cases of two young men with II degree AV block. The first one was a 17 yo asymptomatic boy, soccer player, undergoing 24 hours Holter-ECG for sporadic RVOT ventricular extrasystoles at resting ECG. During the night, an apparent Mobitz type 2 II degree AV block was observed. Detailed analysis showed: Sinusal bradycardia at 50 bpm;Absence of prolongation of P-R intervals before the pause;The pause is longer than double the basic P-P interval;Prolongation of P-P interval in the beats before the pause. The second case was also a young man suffering by atypical episodes of palpitations. The 24h Holter-ECG showed, during the night, an apparent Mobitz type 2 II degree AV block. Also in this case analysis of the tracing highlighted a) progressive slowing of sinus cycle length before the pause b) pause longer than double of sinus cycle and c) absence of prolongation of P-R intervals before the pause. Vagally mediated atrioventricular block and pseudo-Mobitz atrioventricular block. Vagally mediated AV block can have heterogeneous presentation: Wenckebach type, pseudo-Mobitz type II, 2:1, advanced-degree, complete AV block or a combination of different types of AV block and ventricular asystole. The mechanism is mediated by a vagal input, which depresses contemporarily sinus node and AV junction. The site of vagally mediated AV block is usually within the AV node. Generally, it results in a Wenckebach II degree AV block associated with sinus bradycardia, which occurs more often during the night in young/trained people. So the blocked P wave is generally preceded by Wenckebach phenomenon. However, in some patients the prolongation of the P-R interval is not present and the AV block appears abruptly. In these cases, Mobitz type II AV block may be erroneously diagnosed if sinus slowing is ignored. A differential diagnosis between true Mobitz II AV block and pseudo-Mobitz II block is essential for clinical purposes. Simultaneous slowing of the sinus rate and a pause longer than the double of the sinus cycle length indicate clearly a vagal mechanism, ruling out true Mobitz type 2 AV block, especially in young asymptomatic healthy men. In case of doubt, an electrophysiological study may be indicated.

112 A CASE OF INCESSANT SLOW-FAST AVNRT TREATED WITH HIS BUNDLE PACING

Abstract Introduction Slow-fast AVNRT can rarely present as incessant SVT, particularly in patients with increased HV interval. We describe a case of incessant typical AVNRT, treated without transcatheter ablation. Case Presentation An 83-year-old man, with history of PAF, was admitted to our ICU complaining of dyspnea, dizziness and amaurosis. His ECG at presentation depicted sinus bradycardia, first degree AVB (PQ=400 ms) and RBBB (Fig 1A). After betablocker wash-out period, we decided to perform CSP using HBP to ensure AV synchrony and restore physiological pacing. During wash-out period, an incessant regular wide complex tachycardia with RBBB morphology and ventricular rate of 110 bpm occurred: the tracing showed a P wave immediately after the QRS, with RP &amp;lt; PR (Fig 1B). The tachycardia was incessant also in the EP lab. By means of 2 pacing leads (RV lead in the apical septum and RA lead in right appendage) and one diagnostic decapolar catheter (Inquiry, 2-2-2 Abbott) in His region, all connected to the polygraph, we performed an EPS. HV interval in sinus rhythm was 60 ms, AH 340 ms. The electrograms during tachycardia showed HVA sequence and 1:1 VA association, VA&amp;lt; 70 ms, cycle length 520 ms. Pacing from RV lead, we performed the ventricular overdrive pacing maneuver obtaining a VAV response; PPI-TCL was 280 ms and SA-VA difference was 205 ms (Fig 2A). We also noted a VA linking response to atrial overdrive pacing, and AHA response at the end of maneuver excluding JT (Fig 2B). In addition, pacing by the His catheter during tachycardia, we interrupted the arrythmia: the V signal after the last paced beat was not followed by retro-conducted A signal (Fig 2C). Finally, by administrating adenosine 12 mg the tachycardia interrupted with A as last signal recorded (Fig 2D). All these findings were consistent with an incessant typical AVNRT. We chose to treat AVRNT with sequential atrial-His pacing, placing a third lead in His region and programming the device in DDD 70-120, with selective His bundle capture, not correcting the RBBB (Fig 1C, D). Discussion In patients with poor anterograde AV nodal conduction, also slow-fast AVNRT can present as incessant tachycardia. In fact, a shorter sinus cycle length or atrial extrasystole could initiate sufficient delay in anterograde conduction to allow for recovery in conduction in the retrograde direction led to a persistent tachycardia. This case highlights the value of performing EPS diagnostic maneuvers also during PM implantations in order to personalize therapy and programming.

Effect on sinus cycle length and atrioventricular node function after high-power short-duration versus conventional radiofrequency catheter ablation in paroxysmal atrial fibrillation

BackgroundThe efficacy and safety of high-power, short-duration (HPSD) radiofrequency catheter ablation for atrial fibrillation (AF) have been demonstrated in several studies. We aimed to evaluate and compare the effects of the conventional method and the HPSD method for AF ablation on the sinus and AV node function in patients with paroxysmal AF.MethodsThe medical records of patients with paroxysmal AF who underwent pulmonary vein isolation (PVI) were retrieved from a prospectively collected AF ablation registry at a large-sized tertiary center. The HPSD group (n = 41) was distinguished from the conventional ablation group (n = 198) in terms of the power (50 W vs. 20–40 W) and duration (6–10 s vs. 20–30 s) of radiofrequency energy delivery during PVI. Peri-procedural changes in cardiac autonomy were assessed in terms of the changes in sinus cycle length (SCL), block cycle length (BCL), and effective refractory period (ERP) of the atrioventricular node (AVN).ResultsThe SCL, BCL, and ERP of the AVN at baseline and post-ablation were not significantly different between the conventional ablation group and the HPSD group. Shortening of the SCL, BCL, and ERP of the AVN was observed immediately after AF ablation in both groups. One-year recurrence of AF/atrial flutter (35.1% vs. 20.3%; P = 0.011) and atrial flutter (13.8% vs. 4.7%; P = 0.015) were higher in the HPSD group than in the conventional ablation group.ConclusionBoth the HPSD and the conventional ablation method resulted in post-ablation vagal modification as evidenced by the shortening of SCL, BCL, and ERP of the AVN. One-year recurrence of atrial flutter and AF/atrial flutter was higher in patients who underwent the HPSD method.

Tachycardia atrial cycle length equal to that during sinus rhythm: What is the mechanism?

A 64-year-old woman with frequent palpitations presented for atrial fibrillation radiofrequency catheter ablation (RFCA). She had not been administered any antiarrhythmic medication before admission to the hospital. After RFCA, a routine electrophysiological study was performed. Three catheters were positioned: a quadripolar catheter at the high right atrium (HRA), a quadripolar catheter at the His bundle region, and a decapolar catheter in the coronary sinus (CS) (CS 7-8 at the CS ostium). The baseline sinus cycle length was 628 milliseconds (ms), the atrial-His (AH) interval was 87 ms, and the His-ventricular (HV) interval was 52 ms. Antegrade atrioventricular (AV) nodal conduction showed decremental and dual pathways during atrial extrastimulus testing, but no tachycardia was induced. Retrograde ventriculoatrial (VA) conduction showed VA disassociation. Figure 1 shows a narrow QRS complex tachycardia with AV 1:1 conduction that was induced by two spontaneous ventricular extrasystoles. The corresponding intracardiac recording showed that the atrial cycle length oscillated between 627?30 ms (recorded by the HRA catheter) and 626?33 ms (recorded by the CS 7-8 catheter), which was approximately the same as that during sinus rhythm (SR) (Figure 2). How was the tachycardia induced and what is the mechanism of the tachycardia? This article is protected by copyright. All rights reserved.

Wolff-Parkinson-White pattern on alternate beats: What is the mechanism?

The Holter electrocardiogram from an asymptomatic man shows intermittent preexcitation. At the lowest rates all the QRS complexes display a WPW pattern. As the rate increases, preexcitation fails to occur and all the QRS complexes become persistently narrow. With a further increase in sinus rate the WPW occurs on alternate beats and this alternation is maintained for a while. A careful analysis of the accessory pathway conduction in relation to sinus-cycle length and morphology of the prior beat strongly supports the supernormal conduction through the Kent bundle associated with linking as the key mechanism underlying the preexcitation on alternate beats.

Abstract 17454: The Effect of Catheter Ablation on Coronary Sinus Cycle Length in Persistent Atrial Fibrillation

Background: While pulmonary vein isolation (PVI) for treatment of persistent atrial fibrillation (PeAF) is successful in approximately 50%, acute termination of PeAF is rarely observed. Prolongation of cycle length (CL) by 10% is often utilized as an indicator of successful catheter ablation (CA). Objective: To evaluate coronary sinus (CS) cycle length (CL) before and after CA for PeAF. Methods: CA for PeAF was performed in 31 patients (24males, age 63±9 yrs, CHA2DS2-VASc 2.3±1.7, LVEF 49±10%) with PVI, with 4 (13%) also having posterior wall isolation. A multielectrode catheter was placed in the CS and maintained throughout the procedure. CS electrograms were recorded for 10 seconds prior to CA and after completion of CA. No patient reverted to sinus rhythm during CA. CS CL was determined using customized software for activation detection and verified visually, excluding ventricular activation and low quality signals (n=3). The shortest CL among the recording electrodes was used for analysis. Results: CS CL pre- and post-CA were 182.4±23.0 and 191.6± 29.9 ms (p= 0.04) with change from baseline of 5.4±12.7%. The figure shows the histogram for change in CS CL from baseline. Only 7/28 (25%) of patients had CS CL prolongation &gt;10%. Of ten patients who were free of AF off anti-arrhythmic drugs at 1 year, CS CL increased 4.0±6.1%; 2/10 had CS CL prolongation &gt;10%. Of 6 patients with recurrent AF, CS CL increased 13.8±20.7%; 4/6 had CS CL prolongation &gt;10%. Conclusion: Our data demonstrate that CS CL prolongation &gt;10% is not a useful marker of outcomes in patients undergoing catheter ablation for PeAF. This highlights the need to identify other indicators of acute ablation success.

Laser Catheter Modulation of the Sinus Node in the Treatment of Inappropriate Sinus Tachycardia: Experimental and Clinical Results.

Inappropriate sinus tachycardia (IST) is a rare type of arrhythmia that is currently difficult to treat successfully. The effects of laser catheter applications aimed at the sinus nodal area were tested experimentally and the technique was used for the treatment of IST. Continuous-wave, mapping-guided 1,064 nm neodymium-doped yttrium aluminum garnet laser applications at 15 W (9.5 W/mm2) per 15 seconds (142.5 J/mm2) and an irrigation flow of 30 mL/min were aimed at the sinus nodal area in five dogs (three applications each) and one human patient (two applications) by use of an 8-French open-irrigated electrode-laser mapping and ablation (ELMA) catheter provided with three miniature pin electrodes (0.5 mm × 4.0 mm) with interelectrode distances of 2.0 mm arranged symmetrically and radially around the endhole of the catheter tip. Laser application was aimed at the largest and earliest atrial potentials recorded in the focused local electrograms 30 ms to 45 ms prior to the onset of the P-wave in the surface lead electrocardiogram. Lesions were evaluated morphometrically. Holter monitoring in the patient was performed prior to and after treatment. During laser application in the dogs, sinus nodal potential amplitudes dwindled gradually from a mean of 42 mm ± 24 mm to 5.0 mm ± 3.0 mm and sinus cycle lengths lengthened from 452 ms ± 35 ms to 634 ms ± 35 ms (p < 0.0001 for both). In the patient, electrical potential amplitudes in the local electrograms dwindled from 41.0 mm to 5.0 mm and, in the Holter monitor, heart rate decreased from 109 bpm ± 29 bpm to 79 bpm ± 26 bpm (p < 0.0001). IST ablation was painless and without complications. During a follow-up of 4.9 years, the patient was asymptomatic and her heart rate and chronotropic competence remained normal. In conclusion, ablation of IST was achieved by substrate mapping-guided laser application while using the open-irrigated EMLA catheter RytmoLas (LasCor GmbH – Laser Medical Devices, Taufkirchen, Germany). However, this is a proof-of-concept study and further research, preferably in the form of multicenter study trials, is needed for confirmation of the results.

Renal sympathetic denervation induces changes in heart rate variability and is associated with a lower sympathetic tone.

Renal nerve stimulation (RNS) is used to localize sympathetic nerve tissue for selective renal nerve sympathetic denervation (RDN). Examination of heart rate variability (HRV) provides a way to assess the state of the autonomic nervous system. The current study aimed to examine the acute changes in HRV caused by RNS before and after RDN. 30 patients with hypertension referred for RDN were included. RNS was performed under general anesthesia before and after RDN. Heart rate (HR) and blood pressure (BP) were continuously monitored. HRV characteristics were assessed 1min before and after RNS and RDN. RNS before RDN elicited a maximum increase in systolic BP of 45 (± 22)mmHg which was attenuated to 13 (± 12)mmHg (p < 0.001) after RDN. RNS before RDN decreased the sinus cycle length from 1210 (± 201) ms to 1170 (± 203) ms (p = 0.03), after RDN this effect was blunted (p = 0.59). The LF/HF ratio in response to RNS changed from ∆ + 0.448 (± 0.550) before RDN to ∆ - 0.656 (± 0.252) after RDN (p = 0.02). Selecting patients off beta-blockade (n = 11), the RNS-induced changes in HRV components before versus after RDN were more pronounced (LF/HF ratio ∆ + 0.900 ± 1.171 versus ∆ - 0.828 ± 0.519, p = 0.01), whereas changes in HRV parameters in patients on beta-blockade (n = 19) were no longer significant. In patients with diabetes mellitus (n = 7), RNS induced no changes in HRV parameters (LF/HF ratio ∆ - 0.039 ± 0.103 versus ∆ - 0.460 ± 0.491, p = 0.92). RNS induces changes in HRV suggesting increased sympathetic activity. Conversely, after RDN, the RNS-induced changes in HRV suggesting a lower sympathetic autonomic balance. These changes were most pronounced in beta-blocker naïve patients and not present in patients with diabetes mellitus. These findings could support RNS-guided RDN to optimize results.

Renal nerve stimulation identifies aorticorenal innervation and prevents inadvertent ablation of vagal nerves during renal denervation

Purpose: Recently we reported the use of renal nerve stimulation (RNS) during renal denervation (RDN) procedures. RNS induced changes in blood pressure (BP) and heart rate are not fully delineated yet. We hypothesized that electrical stimulation of the sympathetic nerve tissue in the renal artery would lead to an increase in BP and vagal stimulation would cause a decrease in BP. We report the different patterns of BP and heart rate responses elicited by RNS prior to RDN.Methods: 35 patients with drug-resistant hypertension were included. RNS was performed under general anesthesia at four sites in the right and left renal arteries, both before and immediately after RDN. RNS-induced BP and heart rate changes were monitored.Results: A total of 289 RNS sites in 35 patients were analyzed. An increase in systolic BP of >10 mmHg was regarded as a positive BP response to RNS. This pattern of response was observed in 180 sites (62%). 86 RNS sites (30%) showed an indifferent response with BP changes ≤10 mmHg. At 13 sites (4.5%) RNS elicited a decrease in BP up to −8 mmHg. However, 10 RNS sites (3.5%) showed a pronounced vagal response with hypotension and sinus cycle lengths ranging between 4224–10272 milliseconds. These sites were distributed among two patients.Conclusion: RNS identified sympathetic and parasympathetic nerve tissue in the renal arteries. RNS can be potentially used to map nerve bundles and guide selective ablation of sympathetic nerve fibers and prevent inadvertent ablation of parasympathetic nerve tissue during RDN.

COMPARISON OF HEART RATE AND BLOOD PRESSURE RESPONSE TO ULTRASOUND-GUIDED CAROTID SINUS MASSAGE IN THE SUPINE VERSUS UPRIGHT POSITION

Carotid Sinus Massage (CSM) is recommended in the work-up of syncope. Opinions vary as to whether CSM is best done supine or upright to evoke a significant hemodynamic response. CSM was performed in 39 patients ( 23M/16F; age 49±17) undergoing tilt table testing for suspected neurocardiogenic syncope. Right and left Carotid Artery (CA) bifurcations were located by ultrasound (US), marked in ink, and CSM performed at this location supine on the right (RCSMsup) and left (LCSMsup). The participant was then tilted (60°) and CSM repeated 4-6 minutes following tilt on the right (RCSMtilt) and left (LCSMtilt). CSM was done for 10 sec while the breath was held beginning 5 sec after end-expiration. In 17 participants, sham CSM was also done supine (RCSMsham, LCSMsham) while the breath was held and a finger was place on the skin without pressure. The difference (Δ) between maximum sinus cycle length (SCL) during CSM and SCL just prior to CSM, as well as Δ between minimum systolic blood pressure (SBP) during CSM and that just prior to CSM and Δ diastolic (D)BP were measured. No significant ΔSCL was observed with RCSMsham (13±38 ms) and LCSMsham (10±40 ms). SCL prolongation of at least 50 ms (Mean+1SD of sham effect) occurred in 28/39 subjects to at least one of RCSMsup or LCSMsup, but only in 22/39 on tilt. However, there was no statistically significant difference in effect of CSM supine or upright (ΔRCSMsup: 61± 82 ms; ΔRCSMtilt: 42± 89 ms; ΔLCSMsup: 47± 67 ms; ΔLCSMtilt: 38± 52 ms) using t-test or non-parametric testing (Friedmann). Similarly, there was no difference in ΔSBP whether supine or upright (ΔRCSMsup : -7±17 mm Hg; ΔRCSMtilt : -7±17 mm Hg; ΔLCSMsup : -6±12 mm Hg; ΔLCSMtilt: -5±15 mm Hg) or in ΔDBP (ΔRCSMsup: -4±11 mm Hg; ΔRCSMtilt: -5±11 mm Hg; ΔLCSMsup: -4±8 mm Hg; ΔLCSMtilt: -4±11 mm Hg). A non-significant tendency to greater prolongation of SCL in the older group (n = 28; age > 40) with ΔRCSMsup 71±92 ms vs in the younger group (n=11; age ≤ 40) ΔRCSMsup 36±38 ms was absent with tilt and was not observed with LCSM either supine or upright. Using US localization of the CA bifurcation, there is no added value to performing CSM in the upright position compared to supine testing. In fact, there is a tendency to a lesser bradycardic response and no greater BP lowering in the upright position.

Slow conduction through an arc of block: A basis for arrhythmia formation postmyocardial infarction.

The electrophysiologic basis for characteristic rate-dependent, constant-late-coupled (390 + 54 milliseconds) premature ventricular beats (PVBs) present 4-5 days following coronary artery occlusion were examined in 108 anesthetized dogs. Fractionated/double potentials were observed in injured zone bipolar and composite electrograms at prolonged sinus cycle lengths (1,296±396 milliseconds). At shorter cycle lengths, conduction of the delayed potential decremented, separating from the initial electrogram by a progressively prolonged isoelectric interval. With sufficient delay of the second potential following an isoelectric interval, a PVB was initiated. Both metastable and stable constant-coupled PVBs were associated with Wenckebach-like patterns of delayed activation following an isoelectric interval. Signal-averaging from the infarct border confirmed the presence of an isoelectric interval preceding the PVBs (N=15). Pacing from the site of double potential formation accurately reproduced the surface ECG morphology (N=15) of spontaneous PVBs. Closely-spaced epicardial mapping demonstrated delayed activation across an isoelectric interval representing "an arc of conduction block." Rate-dependent very slow antegrade conduction through a zone of apparent conduction block (N=8) produced decremental activation delays until the delay was sufficient to excite epicardium distal to the original "arc of conduction block," resulting in PVB formation. The present experiments demonstrate double potential formation and rate-dependent constant-coupled late PVB formation in infarcted dog hearts. Electrode recordings demonstrate a prolonged isoelectric period preceding PVB formation consistent with very slow conduction (<70 mm/s) across a line of apparent conduction block and may represent a new mechanism of PVB formation following myocardial infarction.

Role of His Refractory Premature Ventricular Complexes in the Differential Diagnosis of a Left Bundle Branch Block Morphology Tachycardia

A 65-year-old man, with no significant past medical history, presented with an episode of sudden onset palpitations and lightheadedness. He was hemodynamically stable and the ECG revealed a left bundle branch block (LBBB) morphology tachycardia at 214 beats per minute (Figure 1A). The tachycardia terminated spontaneously with conversion to normal sinus rhythm and LBBB (Figure 1B). Further evaluation included a 2-dimensional echocardiogram showing a left ventricular ejection fraction of 40% to 45%, left heart catheterization showing angiographically normal coronaries, and cardiac magnetic resonance imaging revealing atypical septal motion with left ventricular ejection fraction of 60% to 65% and no scar or ischemia. The patient underwent an electrophysiology study. At baseline, the sinus cycle length was 890 ms, atrial-His interval was 64 ms, His-ventricular interval was 108 ms, and QRS duration was 120 ms. Spontaneous onset of the LBBB morphology tachycardia after a sinus beat is shown in Figure 2. The tachycardia cycle length is 306 ms, and the His-ventricular interval is 120 ms. The QRS while similar to the LBBB seen during sinus rhythm shows change in axis and the morphology in aVR is predominantly positive. There is no ventriculo-atrial conduction during the tachycardia. Attempts at entrainment from right ventricle (RV) led to termination of the tachycardia. His refractory premature ventricular complexes (PVCs) delivered from RV apex during tachycardia after the His depolarization advances the next H and V (Figure 3). What is the mechanism of the tachycardia? See Editor's Perspective by Asirvatham and Stevenson Figure 1. A , ECG showing wide complex tachycardia with left bundle branch block (LBBB) morphology. B , ECG showing sinus rhythm and LBBB. Figure 2. Spontaneous initiation of tachycardia during sinus rhythm. The first sinus complex does not conduct because of a premature ventricular complexes. The second sinus complex conducts with a His-ventricular (HV) interval of 108 …

Adrenomedullin Stimulates Porcine Sinus Node Automaticity

Adrenomedullin (AM) is a vasodilatory and chronotropic peptide that has cardioprotective properties in settings of ischemia-reperfusion. Specifically, the 52-amino acid peptide hormone has been shown to reduce infarct size and potentially be protective against malignant arrhythmias. AM reduces L-type calcium currents in rabbit ventricular myocytes, and can possibly be utilized as an antiarrhythmic drug. However, at present it is unclear whether AM has cardiac electrophysiological effects in vivo. In the present study, we investigated whether AM affects sinus and atrioventricular nodal functions, cardiac pacing thresholds, refractory properties and intracardiac conduction intervals in an intact porcine model (Norwegian landrace and Yorkshire hybrids; n=12). Hemodynamic and electrophysiological parameters were recorded at baseline and following 60 min of AM-infusion (100 ng/kg/min). The hemodynamic effects of AM were characterized by a reduced mean arterial pressure (76 ± 9 vs. 57 ± 6; p<0.05; mmHg), tachycardia (91 ± 13 vs. 112 ± 15; p<0.05; beats/min) and an augmented cardiac index (131 ± 20 vs. 176 ± 28; p<0.05; ml/min/kg). The sinus cycle length was reduced (674 ± 89 vs. 546 ± 73; p<0.05; ms), sinoatrial conduction time was unaltered (79 ± 24 vs. 72 ± 19; ns; ms), and the sinus node recovery time (SNRT) was reduced at paced cycle lengths of 425 ms, 375 ms and 325 ms (average SNRT 1034 ± 449 vs.704 ± 141; p<0.05; ms). Diastolic pacing thresholds, effective refractory periods, Wenckebach cycle length and intracardiac conduction intervals were unaffected by AM. In conclusion, AM stimulates sinus node function with a reduced sinus cycle length and increased automaticity but has no further detectable intracardiac electrophysiological effects. Whether the increased automaticity is a direct effect on the sinus node or an indirect effect mediated through the autonomic nervous system remains to be determined.