Slow pseudo sinus rhythm and atrial tachycardia of right superior venous pulmonary origin

ABSTRACT Paroxysmal atrial tachycardia usually presents as a sudden acceleration of the atrial rate combined with modifications of the P wave morphology. A 22-year-old patient presented with very fast and very slow atrial ectopic activity. He complained of repetitive episodes of fast tachycardia, some accompanied with dizziness. When the ectopic discharge was slow, no clear-cut difference between the sinus rate and the ectopic rate was seen and thus the atrial rhythm appeared quite regular. The ectopic focus was situated deep inside the right upper pulmonary vein (RSPV). After RSPV isolation a persistent sinus rhythm was established and since then the patient has been asymptomatic for 3 years. Thus, subtle changes in the P wave morphology without a significant change in the heart rate in patients presenting with palpitations can give a clue to the diagnosis of the tachycardia and the localization of the ectopic focus.

Radiofrequency catheter denervation of sinus node: a randomized comparison of right and left atrial approach for the cardioneuroablation

Funding Acknowledgements Type of funding sources: None. Background Radiofrequency catheter ablation of superior paraseptal ganglionic plexus is an important step to eliminate the vagal modulation of sinus node for the treatment of neurally-mediated syncope. The reasonable effect can be achieved by targeting this plexus from the endocardial aspect of both right (RA) and left (LA) atria. Purpose We investigated the efficacy of RA and LA ablation in terms of sinus nodal denervation. Methods The study included 24 patients (age: 42 ± 13 years, 50% males) who underwent cardioneuroablation for recurrent cardioinhibitory syncope in general anesthesia. Right atrial semicircular lesion at the posteroseptal quadrant of superior vena cava ostium was composed of 5-6 equidistantly distributed ablation sites (30 W, 30 s, 20 ml/min). Left atrial lesion of comparable size was placed strictly contralaterally across the interatrial septum in the anterior vestibulum of a right superior pulmonary vein. Patients were randomly (1:1) assigned to RA-to-LA or LA-to-RA ablation. Sinus rate and the response to extracardiac right vagal nerve high-frequency stimulation (50 Hz, 0.05 ms, 1 V/kg [<70V], 5 s) were recorded at baseline and after each ablation cluster. Results Study protocol ablations overall resulted in sinus acceleration (81 ± 13 vs. 59 ± 12 bpm, P <0.0001) and attenuation of inducible sinus arrests (maximum pause: 1.2 ± 1.4 vs. 5.5 ± 3.0 s, P <0.0001). Temporal development of outcome measures with the progression of ablation is shown in the Figure. There was no significant difference between study groups. Irrespective of ablation order, the first ablation cluster on average generated 77% of the final effect on sinus rate and 68% of the final effect on suppression of vagally-induced sinus pauses. Conclusions Neither RA nor LA approach is preferable for targeting the superior paraseptal ganglionic plexus. Both ablation clusters convey complementary and, in part, mutually independent effects. Biatrial cardioneuroablation seems essential for efficacious sinus nodal denervation. Abstract Figure.

Recording Intrinsic Nerve Activity at the Sinoatrial Node in Normal Dogs with High-density Mapping

Background - It is known that autonomic nerve activity controls the sinus rate. However, the coupling between local nerve activity and electrical activation at the sinoatrial node (SAN) remains unclear. We hypothesized that we would be able to record nerve activity at the SAN to investigate if right stellate ganglion (RSG) activation can increase the local intrinsic nerve activity, accelerate sinus rate, and change the earliest activation sites (EASs). Methods - High-density mapping of the epicardial surface of the right atrium (RA) including the SAN was performed in 6 dogs during stimulation of the RSG, and after RSG stellectomy. A radiotransmitter was implanted into 3 additional dogs to record RSG and local nerve activity at the SAN. Results - Heart rate accelerated from 108±4 bpm at baseline to 125±7 bpm after RSG stimulation ( P =0.001), and to 132±7 bpm after apamin injection ( P <0.001). Both electrical RSG stimulation and apamin injection induced local nerve activity at the SAN with the average amplitudes of 3.60±0.72 µV and 3.86±0.56 µV, respectively. RSG stellectomy eliminated the local nerve activity and decreased the heart rate. In ambulatory dogs, local nerve activity at the SAN had a significantly higher average Pearson correlation to heart rate (0.72±0.02, P =0.001) than RSG nerve activity to HR (0.45±0.04 P =0.001). Conclusions - Local intrinsic nerve activity can be recorded at the SAN. Short bursts of these local nerve activities are present before each atrial activation during heart rate acceleration induced by stimulation of the right stellate ganglion.

Inadekvát, aránytalan sinuscsomó-tachycardia: egy régi szívritmuszavar új megvilágításban (II.)

Összefoglaló. Bevezetés: Az inadekvát, aránytalan sinuscsomó-tachycardia a szív nomotop ingerképzési zavarával járó, nem ritka klinikai szindróma. A szívritmuszavar-entitást a nem paroxysmalis, magas nyugalmi sinusfrekvencia, a fizikai/pszichés stresszre adott aránytalan sinustachycardia, valamint főként palpitációs panaszok jellemzik. Célkitűzés: Az aránytalan sinuscsomó-tachycardiás betegeink gyógyszeres kezelésével szerzett tapasztalataink ismertetése. Módszerek: 2008 és 2018 között 104 beteget (92 nő, 12 férfi; átlagéletkor 31 ± 10 év) kezeltünk ezzel a szívritmuszavarral. A betegek kivizsgálásuk után 12 elvezetéses EKG-, terheléses EKG-, valamint 24 órás Holter-monitoros EKG-megfigyeléseken vettek részt a gyógyszeres kezelés előtt és után (bizoprolol: 2 × 5 mg/nap; ivabradin: 2 × 5 mg/nap). Az életminőség változását a European Heart Rhythm Association (EHRA) tüneti skálája szerint állapítottuk meg. Eredmények: Mindkét gyógyszer jelentősen csökkentette a nyugalmi sinusfrekvenciát (kontroll: 102 ± 10/min; bizoprolol: 78 ± 6/min; ivabradin: 74 ± 8/min, mindkettő: p<0,0001). A gyógyszeres kezelés nélküli, 24 órás Holter-monitoros EKG-felvételek során mért szívfrekvenciák (minimum–maximum [átlag] sinusfrekvencia/min) a kontrollértékekről (58 ± 8–159 ± 14 [94 ± 6]/min) mindkét gyógyszerre egyaránt szignifikánsan csökkentek (bizoprolol: 53 ± 7–132 ± 13 [77 ± 9]/min [mindhárom: p<0,0001]; ivabradin 51 ± 6–134 ± 18 [77 ± 8]/min [mindhárom: p<0,0001]). A terheléses EKG-vizsgálatok előtt (kontroll: 99 ± 13/min; bizoprolol 81 ± 11/min [p<0,0001]; ivabradin: 84 ± 10/min [p<0,0001]) és a terhelés csúcspontján mért sinusfrekvenciák (kontroll: 164 ± 15/min; bizoprolol: 140 ± 16/min [p<0,0001]; ivabradin: 142 ± 14/min [p<0,0001]) is jelentősen mérséklődtek. Az azonos dózisban adott két gyógyszer szívfrekvencia-csökkentő hatásai között számottevő különbséget nem tapasztaltunk. Az életminőséget tükröző EHRA tüneti skálán (kontroll: 2,3 ± 0,7) mind a bizoprolol (1,4 ± 1,4; p<0,0001), mind az ivabradin (1,1 ± 0,2; p<0,0001) egyformán csökkentette a betegek tüneteit, panaszait. Számottevő cardiovascularis mellékhatás egyik betegcsoportban sem jelentkezett. Következtetések: Vizsgálati eredményeink alapján megállapítható, hogy az aránytalan sinuscsomó-tachycardiás betegek gyógyszeres kezelésére: (1) a kardiospecifikus adrenerg béta-blokkoló bizoprolol és az If-csatorna-gátló ivabradin egyaránt hatékonynak és biztonságosnak bizonyult; (2) az azonos adagban adott két gyógyszer hatékonysága között számottevő különbség nem volt; (3) a gyógyszeres kezelés nemcsak a sinusfrekvenciát csökkentette, hanem a betegek panaszait, tüneteit is mérsékelte. Orv Hetil. 2020; 161(46): 1953–1958. Summary. Introduction: The inadequate, inappropriate sinus-node tachycardia is not a rare clinical syndrome, defined as a disturbance of the nomotopic impulse formation of the heart. This cardiac arrhythmic entity is characterized by a non-paroxismal, increased sinus rate at rest, and/or inadequate response to physical and/or emotional stress and palpitations. Objective: The aim of this study was to describe our experiences with pharmacological therapy of patients with inappropriate sinus tachycardia syndrome. Methods: Between 2008 and 2018, 104 patients (92 women, 12 men, mean age: 31 ± 10 years) were treated with this cardiac arrhythmia entity. All patients underwent 12-lead ECG, 24-hour Holter-ECG monitoring and standard bicycle dynamic exercise tests before and after drug treatment (bisoprolol: 5 mg bid; ivabradine: 5 mg bid). Changes in the quality of life were estimated by using the European Heart Rhythm Association (EHRA) score. Results: Both drugs decreased significantly the resting heart rate (control: 102 ± 10/min; bisoprolol 78 ± 6/min (p<0.0001), ivabradine: 74 ± 8/min (p<0.0001). The results of the parameters of the 24-hour Holter ECG recordings (expressed as minimal–maximal [average] heart rate/min) with drug therapy showed a significant decrease from control values in all three parameters: control 58 ± 8–159 ± 14 (94 ± 6)/min; bisoprolol 53 ± 7–132 ±13 (77 ± 9)/min (all three: p<0.0001); ivabradine: 51 ± 6–134 ± 18 (77 ± 8)/min (all three: p<0.0001). The sinus rate reduced significantly both before the bicycle dynamic exercise tests (control: 99 ± 13/min; bisoprolol: 81 ± 11/min [p<0.0001]; ivabradine: 84 ± 10/min [p<0.0001]) and at the peaks of the exercise test (control: 164 ± 15/min; bisoprolol: 140 ± 16/min [p<0.0001]; ivabradine 142 ± 14/min [p<0.0001]). The heart rate reducing effects of the two drugs did not differ significantly. The EHRA quality of life score was equally improved by the two drugs (control: 2.3 ± 0.7; bisoprolol: 1.4 ± 1.4 [p<0.0001]; ivabradine: 1.1 ± 0.2 [p<0.0001]). No cardiovascular side effects were observed while taking bisoprolol or ivabradine. Conclusions: Based on our clinical results, it can be pointed out that in the drug therapy of patients with inappropriate sinus node tachycardia: (1) bisoprolol (5 mg bid) and ivabradine (5 mg bid) proved to be equally effective and safe; (2) the heart rate reducing effect of the two drugs – given in the same dosage – did not differ considerably; (3) the pharmacological therapy significantly decreased not only the sinus frequency, but also reduced the symptoms of the patients. Orv Hetil. 2020; 161(46): 1953–1958.

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.

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

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.

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

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<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<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.

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

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.

Sudden heart rate reduction upon optogenetic release of acetylcholine from cardiac parasympathetic neurons in perfused hearts

The balance of sympathetic and parasympathetic tone provides exquisite control of heart rate and contractility and has also been shown to modulate coronary flow and inflammation. Understanding how autonomic balance is altered by cardiac disease is an active area of research and developing new ways to control this balance is providing insights into disease therapies. However, achieving acute neuron-specific stimulation of autonomic neurons can be difficult in experiments that measure the acute effects of nerve stimulation on the heart. Conventional electrical and pharmacological approaches can be spatially and temporally non-selective. Cell-specific expression of light-activated channels (channelrhodopsin, ChR2) is a powerful approach that enables control of the timing and distribution of cellular stimulation using light. We present such an optogenetic approach where parasympathetic cardiac neurons are selectively photoactivated at high temporal precision to initiate cholinergic-mediated slowing of heart rate.Mice were crossbred to express ChR2 in peripheral cholinergic neurons using Cre-Lox recombination driven by a choline acetyltransferase (ChAT) promoter. Hearts from adult mice were excised, perfused, and the epicardium was illuminated (peak 460-465nm) to photoactivate ChR2. In one set of studies, hearts were illuminated using a large-field LED light source. In other studies, a micro LED was placed on the right atrium to selectively illuminate the junction of the superior vena cava and right atrium. The ECG was acquired before, during, and after tissue illumination to measure changes in heart rate. Upon illumination, hearts exhibited sudden and dramatic reductions in heart rate with restoration of normal heart rate after cessation of illumination. Delays in atrioventricular conduction were also observed. Heart rate reductions at the highest irradiance levels were similar to heart rate reductions caused by application of bethanechol (10µM) or acetylcholine (800µM). Atropine (50nM) completely blocked the effect of ChR2 photoactivation, confirming cholinergic mediation.Optogenetic activation of intrinsic parasympathetic neurons reduced heart rate in an immediate, dose-dependent fashion, resembling the slowing of sinus rate in response to acetylcholine. Our results demonstrate a new approach for controlling parasympathetic modulation of cardiac function by selectively activating the endogenous release of acetylcholine from intrinsic cardiac cholinergic neurons.Key MessageOptogenetic photoactivation of intrinsic cardiac neurons provides immediate, tissuespecific stimulation with minimal cross-reactivity. Our results demonstrate that selective expression of channelrhodopsin within cardiac cholinergic neurons enables photoactivated release of acetylcholine, thereby instantaneously slowing sinus rate and altering atrioventricular conduction. This provides for indepth examination of the endogenous interplay between cardiac autonomic neurons and the functional outcomes of downstream post-synaptic receptor activation.