Sinus Rate Research Articles

Pseudo‐Wenckebach

A 47-year-old man with an implanted dual-chamber pacemaker was transferred to the emergency department with acute onset shortness of breath. He had tachycardia, with a heart rate of 123 beats/min in a regularly irregular rhythm. His respiratory rate was 30 breaths/min, and oxygen saturation was 88% with 15-L oxygen via a mask with a nonrebreathing reservoir. The chest X-ray showed bilateral perihilar airspace opacity with dilatation of the main pulmonary artery. An electrocardiogram (Fig. 1A) showed wide-complex tachycardia with regularly irregular RR intervals induced by progressive prolongation of the AV interval. Based on the clinical presentation, a diagnosis of acute pulmonary edema was made. This progressive prolongation of the AV delay is often called “pseudo-atrioventricular Wenckebach.” The pseudo-Wenckebach occurs when the sinus rate exceeds the programmed maximum tracking rate, but the P–P interval is longer than the total atrial refractory period to avoid an abrupt decrease of the ventricular rate that results in circulatory disruption.1, 2 When physicians find irregular P–Q interval, the pseudo-Wenckebach is sometimes mistaken for pacing failure. Therefore, emergency physicians should know this phenomenon. After recovery within a day on nitrates and diuretics, the electrocardiogram (Fig. 1B) showed a normal pacing rhythm. Approval of Research Protocol: Not applicable. Informed Consent: Not applicable . Registry and the Registration No. of the study/Trial: Not applicable. Animal Studies: Not applicable. Conflict of Interest: None declared.

Ultrahigh resolution electroanatomical mapping of the transverse conduction of the right atrial posterior wall in cases with and without typical atrial flutter.

The right atrial posterior wall (RAPW) is known to form a conduction barrier during typical atrial flutter (AFL). We evaluated the transverse conduction properties of RAPW in patients with and without typical AFL using an ultrahigh resolution electroanatomical mapping system. This study included 41 patients who underwent catheter ablation of AF, typical or atypical AFL, in whom we performed RAPW mapping with an ultrahigh resolution mapping system during typical AFL and coronary sinus ostial pacing with three different pacing cycle lengths (PCLs) (1) PCL1: PCL within 40 ms of the AFL cycle length in patients with typical AFL or 250-300 ms for those without, (2) PCL2: 400 ms, (3) PCL3: PCL just faster than the sinus rate. Local RAPW conduction block was evaluated by propagation mapping and local double potentials separated by an isoelectric line. The functional block was defined as areas blocked during shorter PCLs but conductive during longer PCLs. The degree of blockade was calculated by dividing the blocked length by RAPW length(%blockade). Only two patients demonstrated a fixed complete RAPW block (100%, %blockade). Thirty-one patients demonstrated a partial block of RAPW, and the %blockade during PCL1-3 was 49.4 ± 19.8%, 39.5 ± 19.2%, and 35.0 ± 22.9% in this group, respectively. Functional block areas were frequently observed above the fixed block area adjacent to the RA-inferior vena cava junction. Transverse conduction block was more frequently observed in patients with typical AFL at any longitudinal level of RAPW. RAPW transverse conduction block is lower-side dominant and greater in patients with typical AFL than those without.

Outcomes of Pulmonary Vein Isolation in Athletes

The aims of this study were to assess outcomes of pulmonary vein isolation (PVI) performed on athletes at a tertiary care center and to characterize its efficacy and physiological effects. The incidence of atrial fibrillation (AF) is increased in highly trained athletes and poses unique management challenges. Athletes were identified through a database of patients undergoing PVI from January 2000 through October 2015. Outcomes of AF ablation were defined in accordance with published guidelines. Available electrocardiographic, echocardiographic, and exercise treadmill testing data were also analyzed. The study population included 144 athletes (93% men; mean age 50.4 ± 8.6 years; 97 paroxysmal, 38persistent, and 9 long-standing persistent) with median follow-up of 3 years. Single-procedure freedom from arrhythmia was 75%, 68%, and 33% at 1 year for paroxysmal, persistent, and long-standing persistent AF, respectively. Multiple-procedure freedom from arrhythmia off antiarrhythmic drugs was 86%, 76%, and 56% in respective groups at the end of follow-up (mean 1.4 ± 0.7 ablations per athlete). Compared with a matched cohort of nonathletes who underwent PVI, there was no difference in arrhythmia recurrence (log-rank p=0.23). Excluding long-standing persistent AF, longer diagnosis-to-ablation time was the only variable in Cox proportional hazards analyses associated with arrhythmia recurrence (adjusted heart rate per log increase: 1.92; 95% confidence interval: 1.40 to 2.73; p<0.0001), and PVI within 2 years of diagnosis was notably associated with successful outcomes (log-rank p=0.002). Sinus rate increased following the index ablation (mean 54 beats/min vs. 64 beats/min at >1 year; p<0.0001), but maximum metabolic equivalents on exercise treadmill testing were unchanged (13.1 ± 1.2 vs. 12.7 ± 1.4; p=0.44). PVI is an effective therapy in athletes with paroxysmal and persistent AF, and arrhythmia recurrence was no different from that among matched nonathletes. Early ablation was associated with improved success rates. Sustained cardioautonomic effects were observed following ablation, but exercise capacity was preserved.

Predictors of atrial mechanical sensing and atrioventricular synchrony with a leadless ventricular pacemaker: Results from the MARVEL 2 Study

The MARVEL (Micra Atrial TRacking Using a Ventricular AccELerometer) 2 study assessed the efficacy of atrioventricular (AV) synchronous pacing with a Micra leadless pacemaker. Average atrioventricular synchrony (AVS) was 89.2%. Previously, low amplitude of the Micra-sensed atrial signal (A4) was observed to be a factor of low AVS. The purpose of this study was to identify predictors of A4 amplitude and high AVS. We analyzed 64 patients enrolled in MARVEL 2 who had visible P waves on electrocardiogram for assessing A4 amplitude and 40 patients with third-degree AV block for assessing AVS at rest. High AVS was defined as >90% correct atrial-triggered ventricular pacing. The association between clinical factors and echocardiographic parameters with A4 amplitude was investigated using a multivariable model with lasso variable selection. Variables associated with A4 amplitude together with premature ventricular contraction burden, sinus rate, and sinus rate variability (standard deviation of successive differences of P-P intervals [SDSD]) were assessed for association with AVS. In univariate analysis, low A4 amplitude was inversely related to atrial function assessed by E/A ratio and e'/a' ratio, and was directly related to atrial contraction excursion (ACE) and atrial strain (Ɛa) on echocardiography (all P ≤.05). The multivariable lasso regression model found coronary artery bypass graft history, E/A ratio, ACE, and Ɛa were associated with low A4 amplitude. E/A ratio and SDSD were multivariable predictors of high AVS, with >90% probability if E/A <0.94 and SDSD <5 bpm. Clinical parameters and echocardiographic markers of atrial function are associated with A4 signal amplitude. High AVS can be predicted by E/A ratio <0.94 and low sinus rate variability at rest.

NORMOCARDIA – CORRECT HEART RHYTHM

Sinus rhythm is diagnosed based on 12-lead ecg recording. Diagnostic criteria are as follows: positive P waves in limb lead I and II and negative in aVR; PR interval of at least 120 ms; the difference of consecutive P-P interval should be less than 120 ms. A sinus rate limit is between 50-100/min. Numerous factors: physiologic, pathologic, medications, drugs and stimulants could increase sinus rate. Sinus tachycardia is also observed in inappropriate sinus tachycardia and postural orthostatic tachycardia syndrome. ESC guidelines related to latter two syndrome are summarized.

235Anatomic guided ablation of the right ganglionated plexus is enough for cardiac autonomic denervation in patients with significant bradyarrhythmias

Abstract Background In patients with significant bradyarrhytmias, cardiac denervation is an alternative therapeutic approach. Previous reports proposed different methods (as high frequency ednocardial stimulation of ganglionated plexus and specific atrial electrogram identification) and targets (right and left atrial ganglionated plexus) for adequate denervation. There is no consensus on the best way to perform these procedures, in spite the right atrial ganglia plexus (GP) ablation seeming to be the most contributive to its success. Purpose To assess the results of a purely anatomic approach for ablation of just the right atrial plexus in patients with severe vagal bradyarrhytmias. Methods We enrolled patients referred for ablation of cardiac parasympathetic ganglia, with or without atrial fibrillation ablation. We performed eletroanatomic mapping of the right and left atria and used an irrigated tip catheter for ablation, aiming at the anterior right GP at the right pulmonary veins antrum along with ablation at the superior vena cava junction and the inferior right GP at the posterior aspect of the right inferior pulmonary vein along with ablation of the right aspect of the interatrial septum, between the posterior wall and coronary sinus ostium (Figure 1). We assessed the PW and Wenckenback cycle lengths (CL) pre and post procedure in patients with sinus arrest or AV block, respectively, and the patients had new 24h holter readings at least 30 days from the index procedure. Results We enrolled 12 patients: 9 males (75%), median age of 49,5 years (IQR 36-61,75). All patients had structurally normal hearts. 7 patients had only ablation of the parasympathetic ganglia and 5 patients had simultaneous pulmonary vein isolation for previously documented atrial fibrillation. 7 patients (58,3%) had sinus bradycardia (2 patients had sinus arrest with pauses of 8 and 13 seconds), 2 patients with cardioinhibitory syncope (with pauses of 23 and 28 seconds) and 3 patients had transient high degree AV block. The ablation procedure led to a median sinus rate acceleration of 15 bpm (IQR 3-29), a median decrease of 320 ms in PW (IQR 23,75-609,5) in patients with sinus arrest and a decrease of 80 ms in wenckenback CL (IQR 60-200) in patients with AV block. With a median follow up of 133,50 days (IQR 36-61,75), no patient had recurrence of symptoms or conduction disturbances. Conclusions In selected patients with severe functional paroxysmal bradyarrhytmias, cardiac denervation using an ablation strategy purely based on anatomic aspects and targeting only the right GP, seems to be an effective therapeutic approach. Abstract Figure 1: Abl of right ganglionated plex

Cryoballoon pulmonary vein isolation-mediated rise of sinus rate in patients with paroxysmal atrial fibrillation

BackgroundModulation of the cardiac autonomic nervous system by pulmonary vein isolation (PVI) influences the sinoatrial nodal rate. Little is known about the causes, maintenance and prognostic value of this phenomenon. We set out to explore the effects of cryoballoon PVI (cryo-PVI) on sinus rate and its significance for clinical outcome.Methods and resultsWe evaluated 110 patients with paroxysmal atrial fibrillation (AF), who underwent PVI using a second-generation 28 mm cryoballoon by pre-, peri- and postprocedural heart rate acquisition and analysis of clinical outcome. Ninety-one patients could be included in postinterventional follow-up, indicating that cryo-PVI resulted in a significant rise of sinus rate by 16.5% (+ 9.8 ± 0.9 beats/min, p < 0.001) 1 day post procedure compared to preprocedural acquisition. This effect was more pronounced in patients with initial sinus bradycardia (< 60 beats/min.) compared to patients with faster heart rate. Increase of rate was primarily driven by ablation of the right superior pulmonary vein and for a subset of patients, in whom this could be assessed, persisted ≥ 1 year after the procedure. AF recurrence was neither predicted by the magnitude of the initial rate, nor by the extent of rate change, but postprocedural sinus bradycardia was associated with higher recurrence of AF in the year post PVI.ConclusionsCryo-PVI causes a significant rise of sinus rate that is more pronounced in subjects with previous sinus bradycardia. Patient follow-up indicates persistence of this effect and suggests an increased risk of AF recurrence in patients with postprocedural bradycardia.Graphic abstract

Clinical course of sinus node dysfunction after thoracoscopic surgery for atrial fibrillation\u2014analysis of the Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery (AFACT) study

PurposeSinus node dysfunction (SND) may complicate thoracoscopic surgical atrial fibrillation (AF) ablation. Identifying patients at risk is important, as SND may require temporary or permanent pacing. To determine the incidence of postoperative SND and duration of symptoms in patients who underwent thoracoscopic surgical ablation.MethodsPatients with paroxysmal or persistent AF included in the Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery (AFACT) study underwent pulmonary vein isolation and additional left atrial ablations on indication. Patients were randomized to ganglion plexus ablation or control. SND was defined as symptomatic or asymptomatic junctional rhythm exceeding sinus rate within 30 days postoperatively. The SND risk was assessed by using a univariable logistic regression model. The rate of pacemaker implantation was determined.ResultsThe AFACT study included 240 patients. SND developed in 17 (7.1%) patients, not affected by randomized treatment, p = 0.18. SND patients more often had persistent AF (88.2%) than patients without SND (57.4%), p = 0.01. After univariable testing, persistent AF (OR 5.57 CI 1.52–35.90, p = 0.02) and additional left atrial ablations (OR 12.10 CI 2.40–220.20, p = 0.02) were associated with postoperative SND. Six (35.3%) patients needed temporary pacing for 1–7 days; permanent pacemakers (PMs) were implanted for SND in five (29.4%) patients.ConclusionAdditional left atrial ablations strongly increase the SND risk. The majority of SND was temporary, and sinus rhythm resolved within days, which indicates that a conservative approach with regard to pacemaker implantation should be considered.

When Sinus Tachycardia Becomes Too Much: Negative Effects of Excessive Upright Tachycardia on Cardiac Output in Vasovagal Syncope, Postural Tachycardia Syndrome, and Inappropriate Sinus Tachycardia.

Upright posture reduces venous return, stroke volume, and cardiac output (CO) while causing reflex sinus rate (heart rate [HR]) increase. Yet, in inappropriate sinus tachycardia (IST), postural tachycardia syndrome (POTS), and vasovagal syncope (VVS), symptomatic excessive HR occurs. We hypothesized that CO reaches maximum as function of HR in all. We recruited 12 healthy controls, 9 IST, 30 VVS, and 30 POTS patients (13-23years) selected randomly by disorder not by HR, each fulfilled appropriate diagnostic criteria. Subjects were instrumented for electrocardiography, beat-to-beat blood pressure, respiratory rate, CO-Modelflow algorithm, and central blood volume from impedance cardiography; 10-minute data were collected supine; subjects were tilted head-up for ≤10 minutes. We computed phase differences, ΔΦ, between fluctuations of HR (ΔHR) and CO (ΔCO) tabulating data when phases were synchronized, determined by a squared nonlinear phase synchronization index >0.5, describing extent/validity of CO/HR coupling. We graphed results supine, 1-minute post-tilt-up, mid-tilt, and pre-tilt-down using polar coordinates (HR-radius, ΔΦ-angle) plotting cos(ΔΦ) versus HR to determine if transition HR exists at which in-phase shifts to antiphase above which CO decreases when HR further increases. At baseline HR, diastolic and mean arterial pressures in IST and POTS were higher versus controls. Upright HR increased most in POTS then IST and VVS, with diverse changes in CO, SVR, and central blood volume. Each patient grouping was separately and collectively analyzed for HR change showing transition from in-phase to anti-phase (ΔΦ) as HR increased: HRtransition=115±6 (IST), 123±8 (POTS), 124±7 (VVS), P=ns. Controls never reached transitional HR. Excessive HR independently and equivalently reduces upright CO, in IST, POTS, and VVS.

A novel simple, fast, and safe approach for effective superior vena cava isolation using the third-generation cryoballoon.

Superior vena cava (SVC) isolation with radiofrequency energy remains a challenge due to potential side effects, especially phrenic nerve (PN) or sinus node injury. The purpose of this study was to evaluate the feasibility of a novel SVC isolation technique using the third-generation cryoballoon (CB3). Patients undergoing atrial fibrillation (AF) ablation were prospectively included. The procedure was performed with the CB3, beginning with the pulmonary veins and ending with SVC isolation. During applications in the SVC, continuous PN capture and sinus rate were monitored. Once reached SVC isolation during the application, 60 s more was applied, with no bonus application. If after 90 s the SVC was not isolated, application was stopped. A maximum number of four applications were permitted. Thirty patients (62 ± 9 years; 74% male, 78% paroxysmal AF) were included. No SVC activity was observed in two patients. Success rate for SVC isolation was 89%. Mean number of applications per patient was 2.3±1. Mean time to SVC isolation was 37±20 s. Mean duration of application was 92 ± 15 s. Mean total time of procedure for SVC isolation was 218 ± 43s. We recorded only two complications: one transient PN palsy and one short and transient sinus arrest. After a mean follow-up of 5 ± 2 months, 89% are free from arrhythmia recurrence. We present a promising simple SVC-isolation technique using CB3, featuring a high success rate and very low incidence of complications.

Natural History of Subclinical Atrial Fibrillation Detected by Implanted Loop Recorders

BackgroundAs new heart rhythm monitoring technologies emerge, subclinical atrial fibrillation (AF) signifies a future challenge to health care systems. The pathological characteristics of this condition are largely unknown. ObjectivesThis study sought to characterize the natural history of subclinical AF in at-risk patients from the general population. MethodsThe authors studied 590 individuals ≥70 years of age with ≥1 of hypertension, diabetes, previous stroke, or heart failure, without history of AF, undergoing long-term implantable loop recorder monitoring as part of the LOOP (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-risk Individuals) study. Baseline assessments included N-terminal pro–B-type natriuretic peptide (NT-proBNP). All day-to-day heart rhythm and symptom data were extracted from the device. Endpoints included AF burden, AF progression, symptom reports, and heart rate during AF. ResultsA total of 685,445 monitoring days were available for analysis. Adjudicated AF episodes lasting ≥6 min were detected in 205 participants (35%). The AF burden was median 0.13% (interquartile range: 0.03% to 1.05%) of the monitoring time and changed by a factor of 1.31 (95% CI: 1.02 to 1.68) per doubling of NT-proBNP. AF episodes were present 2.7% (interquartile range: 1.0% to 15.7%) of monitoring days after debut. Progression to 24-h episodes was seen in 33 of the AF patients (16%), whereas 46 (22%) had no AF episodes in the last 6 months of monitoring or longer. Symptoms were absent in 185 (90%) at debut, and 178 (87%) never reported AF-related symptoms during follow-up. The averaged heart rate during AF was 96 (interquartile range: 83 to 114) beats/min, 24 (interquartile range: 9 to 41) beats/min faster than daytime sinus rates. ConclusionsAlthough previously unknown AF was highly prevalent, the burden was low, and progression was limited. In addition, symptoms were scarce, and the heart rate was only modestly elevated. (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-risk Individuals [LOOP]; NCT02036450)

Nonspecific intraventricular conduction delay is associated with future occurrence of atrial fibrillation in patients with structurally normal heart

BackgroundWe aimed to elucidate the long-term prognosis of nonspecific intraventricular conduction delay (NIVCD) in patients with structurally normal heart. MethodsWe included 107,838 patients (age, 52.1 ± 15.5 years; men, 46.8%) who underwent electrocardiography in outpatient clinics or medical checkup (unmatched cohort). NIVCD was defined as QRS duration ≥110 ms without meeting the criteria for bundle branch block. Patients with structurally normal heart and sinus rhythm were assigned to the NIVCD and normal QRS groups according to propensity score with matching variables of age, sex, hypertension, and diabetes (matched cohort 1), and additional PR interval (matched cohort 2). Baseline characteristics, electrocardiographic parameters, and clinical outcomes were compared in the unmatched cohort and the matched cohort. ResultsIn the unmatched cohort, the frequencies of male sex and preexisting atrial fibrillation were significantly higher in the NIVCD group than in the normal QRS group. In matched cohort 1 (n = 690), the NIVCD group exhibited significant slower sinus rate and longer PR interval than the normal QRS group. In matched cohort 2 (n = 598), the cumulative incidence of atrial fibrillation was significantly higher in the NIVCD group than in the normal QRS group during a follow-up period of 8.8 ± 2.9 years. NIVCD significantly increased the risk for AF (hazard ratio, 2.571; 95% confidence interval, 1.074–6.156; p = 0.034). ConclusionsIt is suggested that NIVCD may be associated with future occurrence of atrial fibrillation in patients with structurally normal heart and sinus rhythm.

Adaptation of ventricular repolarization duration and dispersion during changes in heart rate induced by atrial stimulation.

BackgroundThe duration of ventricular repolarization (VR) and its spatial and temporal heterogeneity are central elements in arrhythmogenesis. We studied the adaptation of VR duration and dispersion and their relationship in healthy human subjects during atrial pacing.MethodsPatients 20‐50 years of age who were scheduled for ablation of supraventricular tachycardia without preexcitation but otherwise healthy were eligible. Vectorcardiography recordings with Frank leads were used for data collection. Incremental atrial pacing from a coronary sinus electrode was performed by decrements of 10ms/cycle from just above sinus rate, and then kept at a fixed heart rate (HR) just below the Wenckebach rate for ≥5min and then stopped. VR duration was measured as QT and VR dispersion as T area, T amplitude and ventricular gradient. The primary measure (T90 End) was the time to reach 90% change from baseline to the steady state value during and after pacing.ResultsA complete study protocol was accomplished in 9 individuals (6 women). VR duration displayed a monophasic adaptation during HR acceleration lasting on average 20s. The median (Q1‐Q3) T90 End for QT was 85s (51‐104), a delay by a factor >4. All dispersion measures displayed a tri‐phasic response pattern during HR acceleration and T90 End was 3‐5 times shorter than for VR duration.ConclusionsEven during close to “physiological” conditions, complex and differing response patterns in VR duration and dispersion measures followed changes in HR. Extended knowledge about these responses in disease conditions might assist in risk evaluation and finding therapeutic alternatives.

Incidence and predictors of atrial fibrillation episodes as detected by implantable loop recorder in patients at risk: From the LOOP study

Recent studies have suggested a high prevalence of subclinical atrial fibrillation (AF) in various patient populations, and interest in AF screening has increased. However, knowledge about episode duration is scarce, and risk factors for short or long subclinical AF episodes have yet to be recognized. The aim of the study was to assess AF by long-term continuous screening and to investigate predictors of episodes lasting ≥6 minutes, ≥5.5 hours, or ≥24 hours, respectively. A total of 597 patients aged ≥70 years and diagnosed with ≥1 of hypertension, diabetes, previous stroke, or heart failure were recruited from the general population to receive implantable loop recorder with remote monitoring. Exclusion criteria included history of AF or cardiac implantable electronic device. AF episodes were adjudicated by senior cardiologists. During 40 (37; 42) months of continuous monitoring, AF was detected in 209 (35%) of the patients. The cumulative incidences at 3 years were 33.8% (30.2%-37.8%), 16.1% (13.4%-19.4%), and 5.7% (4.1%-7.9%) for AF episodes lasting ≥6 minutes, ≥5.5 hours, and ≥24 hours, respectively. Slower resting sinus rate and higher body mass index, N-terminal prohormone of brain natriuretic peptide, and troponin T at baseline were independently associated with AF detection. Addition of these markers to a model of sex, age, and comorbidities improved prediction of AF episodes ≥24 hours (time-dependent area under the receiver operating characteristic curve 79% vs 65%, P = .037). A considerable burden of previously unknown AF was detected when long-term monitoring was applied in at-risk patients. Biomarkers were associated with AF incidence and improved prediction of long AF episodes.

P3752Ablation of the superior left ganglionic plexus is not necessary for effective denervation of the sinoatrial and atrioventricular nodes

Abstract Background Cardioneuroablation by targeting of atrial ganglionic plexi (GP) has been proposed as a new therapeutic option in selected patients with reflex syncope. Contribution of individual GPs to cardiac autonomic regulations is not fully established. Purpose Because consistent vagal responses have been observed during left superior pulmonary vein isolation in patients undergoing ablation for atrial fibrillation, we investigated whether standalone ablation of the superior left GP modifies the vagal input into the sinoatrial (SAN) and atrioventricular node (AVN). Methods Study hypothesis was investigated in otherwise healthy patients undergoing cardioneuroablation for symptomatic bradyarrhythmias. All had preprocedural atropine test suggesting functional disorder. Anatomically-navigated (CARTO-3) radiofrequency (RF) ablation (25–30 W/30 s/20 ml/min) at empirical GP sites was performed in general anaesthesia. Extracardiac high-frequency vagal nerve stimulation (25–60 V/30–50 Hz/0.05–0.1 ms) via right jugular vein was performed at baseline, after initial superior left GP ablation, and after the ablation of remaining septal and inferior GPs. High-frequency vagal nerve stimulation was always done in both sinus rhythm and atrial pacing. The elimination of all stimulation-induced vagal responses was the endpoint of the procedure. Results A study included 8 patients (34±8 years; 5 males). Six of them had recurrent syncope with cardioinhibitory response at the SAN (n=4), AVN (n=1) or both nodes (n=1); and 2 patients had symptomatic sinus bradycardia. At baseline, high-frequency vagal nerve stimulation induced long episodes of sinus arrest and advanced AV block in all patients. Cluster ablation at the superior left GP (RF time: 192±28 s) did not change the sinus rate (59±14 vs 60±15, NS), PQ interval (174±37 vs 173±37, NS), and did not induce any tangible change in SAN/AVN response to high-frequency vagal nerve stimulation. Subsequently, anterior right GP was targeted from the aspect of right atrium (n=7), from the anterior antrum of right pulmonary veins (n=6), and inferior GPs were targeted from the aspect of left atrium (n=7). This lesion set finally resulted in complete non-responsiveness of SAN and AVN to high-frequency vagal nerve stimulation in all patients. Ablation procedure overall (duration: 172±15 min; RF time: 988±306 s; radiation dose: 70±34 μGy·m2) led to sinus rate acceleration by a median of 29 (IQR: 18–38) bpm, increase of Wenckebach point by 21 (IQR: 9–28) bpm, and shortening of AVN effective refractory period by 40 (IQR: 15–73) ms. Conclusions Cardioneuroablation guided by extracardiac high-frequency vagal nerve stimulation can achieve complete denervation of SAN and AVN by ablation of postero(para)septal and inferior GPs only. Ablation of the superior left GP appears unnecessary and can be eliminated from the lesion set design.

P2565Decreased cardiac pacemaking and attenuated beta-adrenergic response in tric-a knock-out mice

Abstract Background Trimeric intracellular cation (TRIC) channels are expressed on the surface of the sarcoplasmic reticulum and compensate for calcium release from ryanodine receptors. Tric-a knock-out (KO) mice showed diminished calcium release from ryanodine receptors in vascular smooth muscle cells. The cardiac pacemaker is controlled by the surface membrane and intracellular calcium clocks. In spontaneously firing sinus node action potentials, the membrane and calcium clocks work together via numerous interactions modulated by membrane voltage, intracellular calcium release, and protein phosphorylation. Intracellular calcium changes modulate cardiac pacemaking in the sinus node, but the physiological importance of TRIC channels in cardiac rhythm formation is still obscure. Purpose In this study, we aimed to clarify the importance of TRIC channels on cardiac pacemaking using Tric-a KO mice. Methods The expression level of mRNA and proteins in the sinus node was examined by RT-PCR and immunoblotting. Systolic blood pressure was measured with tail-cuff method. Heart rate was measured by ECG, and heart rate variability was examined. The atrial contractile force from isolated hearts was measured with a force transducer. Cardiac action potential and spontaneous sinus rate from isolated hearts were measured with a microelectrode. Isoproterenol was used for sympathetic nerve manipulation. Results Tric-a KO heart showed increased adrenergic β1-receptor expression in immunoblotting. Although there was no significant difference in basal systolic blood pressure between Tric-a KO and wild type (WT) mice, basal heart rate in Tric-a KO mice was significantly lower than that in WT mice (660±10 and 698±10 bpm, n=15 and 19, Tric-a KO mice and WT mice, respectively, p=0.017). Tric-a KO mice showed limited heart rate changes to isoproterenol (24±6 and 99±15 bpm, n=9 and 10, Tric-a KO mice and WT mice, respectively, p&lt;0.001). In the action potential recordings, Tric-a KO atria showed only limited sinus rate changes to isoproterenol (35±9 and 71±10 bpm, n=8 and 6, Tric-a KO mice and WT mice, respectively, p=0.038). WT mice and Tric-a KO mice atrial contractile force showed dose-dependent changes in response to isoproterenol (10–100 nM), but Tric-a KO mice atria showed limited contractile force changes to isoproterenol (116 and 169%, n=7 and 6, Tric-a KO mice and WT mice, respectively, p&lt;0.01). In heart rate variability, Tric-a KO mice showed unstable RR intervals and longer standard deviation of RR intervals than WT mice. Conclusion Tric-a KO mice showed decreased cardiac pacemaking in the sinus node and attenuated responses to beta-adrenergic stimulus, which indicates the involvement of TRIC channels in cardiac rhythm formation and sympathetic nerve regulation.

P1875Nonspecific intraventricular conduction delay is associated with future occurrence of atrial fibrillation in patients with structurally normal heart and sinus rhythm

Abstract Background This study aimed to elucidate long-term prognosis of nonspecific intraventricular conduction delay (NIVCD) in patients with structurally normal heart. Methods We included 107,838 patients (age, 52.1±15.5 years; men, 46.8%) who underwent electrocardiography in outpatient clinics or medical checkup (model 1). NIVCD was defined as QRS duration ≥110 ms and incompatibility with bundle branch block. The patients with structurally normal heart and sinus rhythm were assigned to the NIVCD group and normal QRS group according to propensity score with matching variables of age, sex, hypertension, and diabetes (model 2), and additional PR interval (model 3). Baseline characteristics, electrocardiographic parameters, and clinical outcomes were compared in model 1, 2, and 3, respectively. Results In model 1, the frequencies of male and preexisting atrial fibrillation (AF) were significantly higher in the NIVCD group than in the normal QRS group. In model 2, sinus rate and PR interval were significantly slower and longer in the NIVCD group than in the normal QRS group. In model 3, cumulative incidence of AF was significantly higher in the NIVCD group than in the normal QRS group during follow-up of 8.8±2.9 years (Figure). NIVCD significantly increased risk of AF (hazard ratio, 2.571; 95% confidence interval, 1.074–6.156; p=0.034). NIVCD did not significantly increase risk of sick sinus syndrome, complete atrioventricular block, and heart failure. Atrial fibrillation-free survival Conclusions NIVCD is associated with slow sinus rate and prolonged PR interval. NIVCD is an independent risk factor of AF in patients with structurally normal heart.

Minimally invasive thoracoscopic surgery is an effective approach for treating inappropriate sinus tachycardia.

Inappropriate sinus tachycardia (IST) is characterized by increased heart rate out of proportion to normal physiologic demand. IST ablation is challenging for the electrophysiology community due to the epicardial location of the sinus node and the risk of phrenic nerve (PN) injury during catheter ablation. In this study, we investigated the safety and efficacy of a minimally invasive thoracoscopic surgery for elimination of IST. Patients with IST who failed medical therapy or endocardial ablation underwent minimally invasive thoracoscopic epicardial ablation. Epicardial activation mapping was performed to identify the earliest activation site and any possible migration of earliest activation along the lateral right atrium. The PN in each patient was protected by a pericardial retraction suture. From 1 January 2000 to 15 June 2018, 10 patients (eight females and two males) underwent minimally invasive thoracoscopic IST ablation. Mean age of the patients was 36.7 ± 12.5 years. Mean baseline sinus rate was 113.8 ± 21.8 beats per minute. After surgery, the mean heart rate significantly decreased to 79.8 ± 8.2 at postoperative day 1 and to 75.8 ± 8.1 at day 30 (both P < .001). No in-hospital death, stroke, or PN injury occurred. One patient required reintubation, one patient developed postoperative pericarditis, and another patient had a pulmonary embolus. Median follow-up was 6 months (range, 1-50). Freedom from reintervention was 88% at 6 months. Minimally invasive thoracoscopic ablation for IST is a safe and effective approach that preserves the phrenic nerve. Due to the possibility of IST activation site migration, continued follow-up after surgery is required.

Vagus Nerve Stimulation Attenuates Hepatic Ischemia/Reperfusion Injury via the Nrf2/HO-1 Pathway.

It has been demonstrated that vagus nerve stimulation (VNS) plays a protective role in ischemia/reperfusion (I/R) injury of various organs. The present study investigates the protective effect of VNS on hepatic I/R injury and the potential mechanisms. Male Sprague-Dawley rats were randomly allocated into three groups: the sham operation group (Sham; n = 6, sham surgery with sham VNS); the I/R group (n = 6, hepatic I/R surgery with sham VNS); and the VNS group (n = 6, hepatic I/R surgery plus VNS). The I/R model was established by 1 hour of 70% hepatic ischemia. Tissue samples and blood samples were collected after 6 hours of reperfusion. The left cervical vagus nerve was separated and stimulated throughout the whole I/R process. The stimulus intensity was standardized to the voltage level that slowed the sinus rate by 10%. VNS significantly reduced the necrotic area and cell death in I/R tissues. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were also decreased by VNS. In addition, VNS suppressed inflammation, oxidative stress, and apoptosis in I/R tissues. VNS significantly increased the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) in the liver. These data indicated that VNS may attenuate hepatic I/R injury by inhibiting inflammation, oxidative stress, and apoptosis possibly via the Nrf2/HO-1 pathway.

Early short-term ivabradine treatment in new-onset acute systolic heart failure and sinus tachycardia patients with inflammatory rheumatic disease.

Acute heart failure (AHF) is a common complication of inflammatory rheumatic disease (IRD) and usually coexists with tachycardia. Ivabradine, a direct sinus node inhibitor, which was proven to have favorable effects in patients with chronic HF (CHF), has not been sufficiently evaluated in AHF patients regarding its efficacy and safety. The present study sought to explore the effectiveness of early short-term ivabradine treatment in new-onset AHF and concurrent sinus tachycardia in patients with IRD. A total of 12 consecutive patients with IRD, who had new-onset AHF and concurrent sinus tachycardia, were prescribed ivabradine and were retrospectively recruited. Standard medication therapy for AHF was also administered. The heart rate (HR), left ventricular ejection fraction (LVEF), biomarkers of HF and New York Heart Association (NYHA) classification score were compared prior to and after ivabradine treatment. After 48 h of treatment with ivabradine, the mean resting HR decreased from 118.0±13.8 to 83.3±7.3 bpm (P<0.001). Transthoracic echocardiography indicated a significant improvement in the LVEF on an average of 2 weeks after ivabradine prescription when compared with the baseline evaluation (51.2±8.4 vs. 38.0±9.0%; P<0.001). In addition, ivabradine treatment resulted in significantly decreased N-terminal proB-type natriuretic peptide (4,900±3,672 vs. 16,806±16,130 pg/ml; P=0.045) and improvement of the NYHA classification score (2.3±0.6 vs. 3.5±0.5; P<0.001) at 2 weeks when compared with the baseline. Overall, the results of the present study suggested that early use of ivabradine is safe in IRD patients with new-onset AHF and enhances the sinus rate reduction, which may improve heart function.