Sinus Rate Research Articles

Sympathetic toggled sinus rate acceleration as a mechanism of sustained sinus tachycardia in chronic orthostatic intolerance syndrome

The role of sympathetic nerve activity to maintain sinus rate acceleration remains unclear. The purpose of this study was to test the hypothesis that sustained (>30 seconds) sinus rate acceleration can be associated with either a sympathetic driven or a sympathetic toggled mechanism. We used a patch monitor to record skin sympathetic nerve activity (SKNA) and electrocardiogram over 24 hours. Study 1 included chronic orthostatic intolerance (OI) (n = 18), atrial fibrillation (n = 7), and asymptomatic normal control (n = 19) groups. Study 2 included 17 participants with chronic OI not treated with ivabradine, pyridostigmine, or β-blockers. While a majority of sinus rate acceleration was driven by persistent SKNA in study 1, some episodes were toggled on and off by SKNA bursts without persistent SKNA elevation. The sympathetic toggled sinus rate acceleration episodes were found in 7 of 18 participants with chronic OI (39%), 2 of 7 participants with atrial fibrillation (29%), and 6 of 19 normal control participants (32%) (P = .847) and were faster and longer in the chronic OI group than in other groups. In study 2, there were a total of 11 episodes of sinus rate acceleration that persisted for >200 seconds. Among these episodes, 6 (35%) were toggled on and off by SKNA bursts. Sustained sinus rate acceleration (may be toggled on or off) is associated with SKNA bursts in participants with chronic OI, participants with atrial fibrillation, and normal controls. Patients with OI had more frequent and longer episodes than did other groups.

Inappropriate sinus tachycardia: an examination of existing definitions.

Inappropriate sinus tachycardia (IST) is a syndrome characterized by an elevated sinus rate unassociated with known physiological, pathological, or pharmacological causes. Despite published consensus documents, IST definitions appear to vary in the literature. In this study, we reviewed IST publications to evaluate IST definition variability and ascertain the degree to which consensus definitions are being adopted. English-language articles in PubMed, Ovid MEDLINE, Ovid Embase, and Google Scholar published from 1 January 1970 to 1 June 2021 with the title terms 'inappropriate sinus tachycardia,' 'non-paroxysmal sinus tachycardia,' or 'permanent sinus tachycardia' were searched. In each, the IST definition used, qualifying characteristics, and publications cited to support each definition were recorded. We identified 138 publications meeting the search criteria. Inappropriate sinus tachycardia definitions were provided in 114 of 138 articles (83%). A majority of definitions (92/114, 81%) used distinct heart rate (HR) thresholds. Among these, the most common threshold was ≥100 beats per minute (BPM) (75/92, 82%), mainly measured at rest (54/92, 59%). Most definitions (47/92, 51%) included a second criterion to qualify for IST; these were most often an HR threshold of 90 BPM measured over 24 h by ambulatory electrocardiogram (37/47, 79%). Diagnosis of exclusion was a common criterion (75/92, 82%) but symptom status was not (41/92, 45%). The 2015 Heart Rhythm Society IST consensus was commonly cited but adopted in only 37% of definitions published after 2015. Inappropriate sinus tachycardia definitions in current literature are inconsistent, and professional society consensus IST definitions have, to date, had limited impact.

What Is the Mechanism of This Cardiac Rhythm?

An 80-year-old man with syncope was admitted for evaluation. His clinical examination revealed nothing remarkable. He had no history of heart disease, his blood pressure and electrolyte levels were normal, and he was taking no medications known to cause bradyarrhythmia. Overnight telemetry revealed the electrocardiogram displayed below (Fig. 1).The rhythm strip suggests which diagnosis?D) Junctional escape and intermittent capture beatsThe telemetry strip displayed junctional rhythm, sinus capture after every second junctional rhythm, and right bundle branch block (RBBB) of the sinus-captured beat (Fig. 2). This rare phenomenon, wherein a sinus-captured beat occurs after 2 junctional escape beats, is termed escape-reentry-capture trigeminy.1In isorhythmic atrioventricular (AV) dissociation (Answer A), the atria and ventricles beat at the same rate but are dissociated from each other; here, however, the junctional beat with retrograde conduction to the atria rules out dissociation between competing rhythms. The lack of clear P waves preceding the QRS complexes and the absence of progressive PR prolongation makes Mobitz type I AV block (Answer B) unlikely. Premature ventricular contractions in trigeminy (Answer C) are unlikely because the wide complexes with RBBB morphology are preceded by a P wave, and the QRS pattern simulates a “typical” RBBB. The 2 junctional beats followed by P-wave capture makes premature atrial complexes in trigeminy (Answer E) unlikely.Escape-reentry-capture occurs in the presence of sinus nodal dysfunction (sick sinus syndrome) when the sinus impulse rate is slower than the junctional escape rate. The inverted P wave in Figure 2 (arrows) suggests that the first junctional beat was conducted retrograde to the atria, that the next junctional beat was not, and that the subsequent sinus beat was conducted with an RBBB. This aberrancy may be explained by the “long-short” sequence that prolongs the effective refractory period of the right bundle. Consequently, the sinus rate was apparently slow enough to be captured in a trigeminal pattern. Note also that the junctional rhythm did not affect the sinus rate. The patient was given a permanent pacemaker. This case illustrates the escape-reentry-capture phenomenon in a trigeminal pattern caused by sinus nodal dysfunction.Conflict of Interest Disclosure: NoneFunding/Support: None

Novel multi-site, multi-point biventricular pacing configuration: acute haemodynamic benefit

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Supported by the research grant of the AZV (Ministry of Health of the Czech Republic) Background Biventricular pacing (BVP) using multiple left ventricular (LV) sites may augment the hemodynamic effect of cardiac resynchronisation therapy (CRT) by engaging a greater mass of the myocardium. Purpose To evaluate the acute hemodynamic effect of a novel multi-site, multi-point BVP configuration. Methods The study investigated 18 patients with idiopathic dilated cardiomyopathy and left bundle-branch block during implantation of a BVP device (age: 59 ± 14 years, female gender: 7 [39%], LVEF: 27 ± 6%, native QRS: 171 ± 16 ms). Conventional leads were placed in the right atrium (RA) and ventricle (RV), one quadripolar LV lead (Quartet, Abbott, Abbott Park, IL, USA) was positioned in the posterolateral and another one in lateral or anterolateral coronary vein. Individual bipoles of all leads were connected through a splitter to separate external cardiac stimulators. Hemodynamics was evaluated using a micromanometer-tipped catheter (Micro-Cath, Millar, Tx, USA) located in the LV during RA pacing above sinus rate and five atrio-ventricular sequential pacing configurations at the same rate: 1.) RA+RV, 2.) RA + RV + distal bipole of the LV lead with greater dP/dT („conventional BVP"), 3.) RA + RV + distal and proximal bipoles of the LV lead with greater dP/dT („single-lead multi-point BVP"), 4.) RA + RV + distal bipoles of both LV leads („two-lead multi-site BVP"), and 5.) sequentional pacing RA + RV + all bipoles of both LV leads interconnected to a mesh („maximum BVP"). Results Compared to RA pacing, LV dP/dT was significantly greater during all BVP pacing configurations (RA pacing: 1940 ± 507 mmHg/s vs. conventional BVP: 2431 ± 855 mmHg/s, single-lead multi-point BVP: 2539 ± 740 mmHg/s, two-lead multisite BVP: 2517 ± 836 mmHg/s, and "maximum BVP": 2685 ± 893 mmHg/s, all p<0.001, Figure 1), but not during RA-RV pacing (2014 ± 721 mmHg/s, p=0.12). In addition, dP/dT was significantly greater during "maximum BVP" compared to conventional BVP (p=0.05). Conclusion Compared to RA pacing and conventional BVP, the greatest increase in LV contractility was achieved with a novel multi-site, multi-point "maximum BVP" configuration. These preliminary findings provide a rationale for designing new approaches to CRT.

Electrophysiological differences of deep sedation with dexmedetomidine versus propofol

Abstract Funding Acknowledgements Type of funding sources: None. Background Dexmedetomidine and propofol are commonly used drugs for deep sedation during cardiovascular interventions. Patients undergoing these interventions often have impaired sinus node function or atrioventricular (AV) conduction disease. Anesthetics used for deep sedation may further compromise sinus node function and AV nodal conduction, and thereby interfere with the intervention. Purpose To compare the electrophysiological effects of dexmedetomidine and propofol on the function of the sinus node and AV conduction. Methods We randomized patients undergoing first atrial fibrilation ablation 1:1 to deep sedation by dexmedetomidine (DEX group) versus propofol (PRO group), according to a standardized protocol. At the end of the ablation procedure with the patients still deeply sedated and hemodynamically stable, we conducted a standard electrophysiological study and assessed sinus node function, properties of AV conduction and atrial refractoriness. Results Of 160 patients (65±11 years old; 32% female) included into the study, 80 patients were randomized to the DEX and PRO group each. Procedure duration (128±59 minutes) and sedation depth, as assessed by the "Modified Observer’s Assessment of Alertness/Sedation" score (median 3; interquartile range 2, 3), was not different among groups. DEX group patients received a mean of 231±111 mcg of dexmedetomidine and PRO group patients a mean of 657±356 mg of propofol. The table shows the results of the electrophysiological study. DEX group patients had lower sinus rate and longer unadjusted sinus node recovery time (SNRT) at pacing cycle lengths of 600, 500 and 400 ms. However, both corrected (SNRT-RR) and normalized (SNRT/RR) SNRT did not differ among groups. Compared to PRO group patients, AV nodal conduction was slower in DEX group patients as evidenced by longer PR and AH intervals, and a higher Wenckebach cycle length and AV node effective refractory period (ERP) was observed. Conduction properties in the His-Purkinje system were not different among groups, as QRS width and HV interval were similar. An arrhythmia, mainly atrial fibrillation, was induced in 33 patients (21%) during the electrophysiological study, without differences among groups. Conclusions Sinus rate and AV conduction are slower during deep sedation with dexmedetomidine compared to propofol. These differences in electrophysiological effects need to be taken into account when using these anesthetics during cardiovascular interventions.

Anatomically-guided cardioneuroablation for recurrent neurally mediated syncope

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardioneuroablation (CNA) has been proposed as a new therapeutic approach in selected patients with recurrent neurally mediated syncope and documented cardioinhibitory component. Purpose We report on procedural data and clinical outcomes of consecutive patients who underwent anatomically-guided CNA at our center in the period of 2014 - 2021. Methods A study investigated 145 otherwise healthy patients (age: 40 ± 14 years, 56% males) with recurrent reflex syncope and the physiological result of the atropine test. Biatrial radiofrequency (RF) ablation was performed under general anesthesia by irrigated-tip catheter at empirical sites of ganglionated plexi (GP) with the navigation by CARTO-3 system and intracardiac echocardiography. Anterior right GP and posteromedial left GP were always targeted to modulate the innervation of both sinoatrial (SAN) and atrioventricular (AVN) nodes, irrespective of clinical manifestation of the disease. The loss of responsiveness of both nodes to extracardiac vagus nerve stimulation was the procedural endpoint. Right vagus or bilateral vagus nerve stimulation was used in 86% and 54% of procedures, respectively. Results Enrolled patients had documented cardioinhibitory disorder of SAN (59%), AVN (30%), or both nodes (11%). CNA (duration: 157 ± 31 min; RF time: 15 ± 6 min; radiation dose: 84 ± 135 µGy.m²) resulted in sinus rate acceleration by 28 ± 12 bpm, shortening of AH interval by 15 ± 31 ms, an increase of Wenckebach point by 28 ± 33 bpm, shortening of AVN effective refractory period by 110 ± 115 ms, and sinus node recovery time by 508 ± 666 ms. During a median follow up of 26 (IQR: 12-39) months, CNA was repeated in 9 patients and is scheduled in 3 other (total 8%). Pacemaker was implanted only in 4 (3%) patients after single (n = 2) or repeated CNA (n = 2). Corresponding Kaplan-Meier curves are provided in the Figure. Any-syncope-free survival is comparable to that reported in active arms of historical and recent pacemaker studies. Conclusions CNA is a reasonably effective treatment option for patients with functional cardioinhibitory syncope. CNA can be performed by anatomically-guided ablation at empirical GP sites. Our study corroborates the clinical utility of CNA as a viable alternative to pacemaker implant in selected patients.

Leadless atrioventricular synchronous pacing in an outpatient setting: Early lessons learned on factors affecting atrioventricular synchrony

Leadless pacemakers (PMs) capable of atrioventricular (AV) synchronous pacing have recently been introduced. Initial feasibility studies were promising but limited to just a few minutes of AV synchronous pacing. Real-world, long-term data on AV synchrony and programming adjustments affecting AV synchrony in outpatients are lacking. The purpose of this study was to investigate AV synchrony and influences of PM programming adjustments in outpatients with leadless VDD PMs. All patients who received a leadless VDD PM (Micra™ AV, Medtronic) between July 2020 and May 2021 at our center were included in this observational study. AV synchrony was assessed repeatedly postoperatively and during follow-up using Holter electrocardiographic (ECG) recordings. AV synchrony was defined as a QRS complex preceded by a p wave within 300 ms. The impact of programming changes during follow-up on AV synchrony was studied. A total of 816 hours of Holter ECG from 20 outpatients were analyzed. During predominantly paced episodes (≥80% ventricular pacing), median AV synchrony was 91% [interquartile range (IQR) 34%-100%] when patients had sinus rates 50-80/min. Median AV synchrony was lower when patients had sinus rates >80/min [33% (29%-46%); P <.001]. During a stepwise optimization protocol, AV synchrony could be improved (P <.038). Multivariate analysis showed that a shorter maximum A3 window end (P <.001), lower A3 threshold (P = .046), and minimum A4 threshold (P<.001) improved AV synchrony. Successful VDD pacing in the outpatient setting during higher sinus rates is more difficult to achieve than can be presumed based on initial feasibility studies. The devices often require multiple reprogramming to maximize AV sequential pacing.

PO-623-06 LIMITED CARDIO-NEURAL ABLATION OF THE SUPERIOR VENA CAVA-AORTA AND RIGHT SUPERIOR GANGLIONATED PLEXI AS AN ADJUNCT TO PULMONARY VEIN ISOLATION FOR TACHY-BRADY SYNDROME

Use of negative chronotropic agents in atrial fibrillation (AF) can cause symptomatic sinus bradycardia (tachy-brady syndrome), often leading to pacemaker implantation. Limited cardioneural ablation (CNA) of ganglionated plexi (GPs) immediately following radiofrequency ablation (RFA) for AF can increase heart rate (HR) by modifying autonomic tone, which may help avoid device implantation. To explore limited CNA for sinus HR augmentation as an adjunct to RFA for AF in patients with tachy-brady syndrome and to determine if increases in sinus HR are sustained. We performed CNA of the right superior and superior vena cava (SVC)-aorta GPs in 11 patients following RFA for AF. All patients had resting sinus bradycardia (HR<60 bpm). Ten patients were male, age 62 ± 11 years (all data mean ± SD), paroxysmal AF in 5 cases, repeat AF procedure in 3 cases, posterior wall isolation / additional lines in 9 cases. All procedures were performed under general anesthesia with jet ventilation. GPs were identified by fractionated electrograms in typical anatomic locations with HR increase during ablation. Intra-procedural HR was obtained following AF ablation immediately before and after CNA. Ambulatory sinus HR was collected from 12 lead ECGs before ablation and at 2 week and 2 month post-procedure visits. Intra-procedural HR increased immediately following CNA from 48 ± 10 bpm to 78 ± 15 bpm, p<0.001, median increase 36 bpm. Compared to pre-procedure ambulatory HR (53 ± 7 bpm), post-procedure HR increased to 65 ± 9 bpm at 2 week and 73 ± 11 bpm at 2 month follow-up visits (p<0.05). One patient developed post-procedure bradycardia due to suspected sinus node artery injury requiring temporary dopamine infusion but no permanent pacing. In 2 cases, antiarrhythmic drugs were stopped during follow-up, but beta blockers were continued unchanged in all patients. Limited CNA of the SVC-aorta and right superior GPs as an adjunct to AF ablation resulted in an immediate HR increase that was sustained over 2 months of follow-up. This strategy may be useful in augmenting sinus rates in patients with tachy-brady syndrome.

PO-650-08 VALUE OF ATROPINE TEST TO ESTIMATE THE CARDIONEUROABLATION RESULT

Vagal innervation keeps an autonomic tone that predominates most of the time. Because of this, the isolated sinus heart rate (HR) is higher than the in-situ sinus rate. Atropine stops vagal action by blocking muscarinic receptors in the heart. Several studies have shown that cardioneuroablation (CNA) also promotes blocking of vagal action by partially eliminating the postganglionic parasympathetic neuron. Thus, when CNA is performed, there is typically an increase in HR. Previously knowing whether HR will increase with CNA is critical information since CNA is not indicated if there is no atropine response.

A Rhythmic Electrocardiographic Pattern in an Older Adult With Chest Pain.

Scenario: An 87-year-old woman with a history of atrial fibrillation, hypertension, and hyperlipidemia came to the emergency department with substernal chest pain that was not relieved with nitroglycerin. She was found to be in atrial fibrillation with rapid ventricular response and had dynamic troponin levels that were concerning for myocardial infarction. Left-sided cardiac catheterization revealed severe coronary disease with about 80% occlusion of the left main and left anterior descending coronary arteries; however, percutaneous coronary intervention (PCI) was not done because of the patient’s hemodynamic instability. After the catheterization, she continued to have substernal chest pain for 2 days and was taken back for emergent PCI with temporary mechanical ventricular support. Two drug-eluting stents were placed. Her bedside electrocardiography (ECG) strip after the emergent PCI is shown here.Atrial bigeminy with a sinus rate of 35 beats per minute and right bundle branch block (RBBB).This patient exhibited multiple deficits in conduction due to acute occlusion of the left main and left anterior descending (LAD) coronary arteries leading to infarction of the surrounding myocardium. The left main coronary artery arises from the aorta, passes between the pulmonary trunk and the left atrial appendage, and bifurcates into the LAD and the left circumflex coronary artery. The LAD, of interest in this example, supplies oxygenated blood to the interventricular septum and left ventricle. Occlusion of both the left main and LAD coronary arteries likely led to the atrial bigeminy and RBBB seen here.Occlusion of the left main coronary artery can induce ischemia in the left atrium and left atrial appendage, propogating atrial bigeminy, a regularly irregular rhythm where a premature atrial contraction (PAC) follows each normal sinus beat (N). Ischemia propagates spontaneous electrical activity such as PACs and disrupts normal conduction. When another region of the atria depolarizes before the sinoatrial node, PACs occur; the PACs may be sporadic or patterned (eg, bigeminy, trigeminy). On an ECG, PACs may show a P wave morphology different from the sinus beat or no P wave preceding the QRS complex. If the P wave preceding the QRS complex is not visible, the P wave is most likely embedded in the preceding T wave. Both PACs and sinus beats travel down the same conduction pathway to the ventricle, producing a morphologically similar QRS complex; this feature differentiates PACs from premature ventricular contractions, which have grossly different morphologies, unless there is an existing BBB (as here), which makes distinguishing PACs from premature ventricular contractions challenging.The wide QRS complexes with slurred qRs morphology in lead V1 and the discordant T waves are due to RBBB, most likely caused by the occlusion of the LAD. In about 90% of patients, the proximal LAD septal perforators perfuse the right bundle branch and the anterior fascicle of the left bundle branch. Thus, occlusion of the LAD may have caused subsequent ischemia in the intraventricular septum, slowing conduction through the bundle branches and inducing an RBBB in this patient. Importantly, an RBBB does not preclude assessment of ST-segment elevation indicative of transmural ischemia due to coronary occlusion, but since it is unknown if the RBBB was preexisting, it is best to review a previous ECG tracing.After emergent PCI, the patient developed atrial bigeminy and remained in the irregular rhythm for 6 hours. She did not develop new ischemic symptoms and did not require more interventions. She remained clinically unstable with a bradycardic sinus rate in atrial bigeminy, but no signs or symptoms of hypoperfusion were noted. The bedside nurse closely monitored the patient and the ECG because atrial bigeminy can progress to atrial fibrillation. Optimal guideline-based therapies for acute coronary syndrome, including dual antiplatelet therapy, are indicated to maintain stent patency. Careful monitoring of the ST segments for ischemia is indicated.

Resveratrol and regular exercise may attenuate hypertension-induced cardiac dysfunction through modulation of cellular stress responses

AimsHypertension is one of the major causes of cardiac damage. In this study, the effects of resveratrol supplementation and regular exercise on hypertension-induced cellular stress responses of myocardium were compared. Main methodsHypertension was induced in male Wistar rats by deoxycorticosterone-acetate + salt administration for 12 weeks. Resveratrol and regular exercise were applied for the last six weeks. In addition to biochemical and molecular examinations, isoprenaline, phenylephrine and, acetylcholine-mediated contractions and sinus rate were recorded in the isolated cardiac tissues. Key findingsResveratrol and regular exercise reduced systolic blood pressure in hypertensive rats. The altered adrenergic and cholinergic responses of the right atrium and left papillary muscles in hypertension were separately improved by resveratrol and regular exercise. Resveratrol and regular exercise decreased plasma and cardiac total antioxidant capacity and, augmented the expression of antioxidant genes in hypertensive rats. While regular exercise restored the increase in p-PERK expression associated with endoplasmic reticulum stress and decrease in mitophagic marker PINK1 expression, resveratrol only ameliorated PINK1 expression in hypertensive rats. Resveratrol and exercise training suppressed hypertension-induced NLRP3 inflammasome activation by reversing the increase in NLRP3, p-NF-κB expression and the mature-IL-1β/pro-IL-1β and cleaved-caspase-1/pro-caspase-1 ratio. Resveratrol and exercise enhanced mRNA expression of caspase-3, bax, and bcl-2 involved in the apoptotic pathway, but attenuated phosphorylation of stress-related mitogenic proteins p38 and JNK induced by hypertension. SignificanceOur study demonstrated the protective effect of resveratrol and exercise on hypertension-induced cardiac dysfunction by modulating cellular stress responses including oxidative stress, ER stress, mitophagy, NLRP3 inflammasome-mediated inflammation, and mitogenic activation.

Sinus Node Sparing Hybrid Thoracoscopic Ablation Outcomes in Patients with Inappropriate Sinus Tachycardia (SUSRUTA-IST) Registry.

Medical treatment of inappropriate sinus tachycardia (IST) remains suboptimal. Radiofrequency sinus node (RF-SN) ablation has poor success and higher complication rates. We aimed to compare clinical outcomes of the novel SN sparing hybrid ablation technique with those of RF-SN modification for IST management. This is a multicenter prospective registry comparing the SN sparing hybrid ablation strategy with RF-SN modification. The hybrid procedure was performed using an RF bipolar clamp, isolating superior vena cava/inferior vena cava with the creation of a lateral line across the crista terminalis while sparing the SN region (identified by endocardial 3-dimensional mapping). RF-SN modification was performed by endocardial and/or epicardial mapping and ablation at the site of earliest atrial activation. Of the 100 patients (hybrid ablation group, n = 50; RF-SN group, n = 50), 82% were women, and the mean age was 22.8 years. Normal sinus rhythm and rate were restored in all patients in the hybrid group (vs 84% in the RF-SN group; P = .006). Hybrid ablation was associated with significantly better improvement in mean daily heart rate and peak 6-minute walk heart rate compared with RF-SN ablation. The RF-SN group had a significantly higher rate of redo procedures (100% vs 8%; P < .001), phrenic nerve injury (14% vs 0%; P = .012), lower acute pericarditis (48% vs 92%; P< .0001), permanent pacemaker implantation (50% vs 4%; P<.0001) than did the hybrid ablation group. The novel sinus node sparing hybrid ablation procedure appears to be more efficacious and safer in patients with symptomatic drug-resistant IST with long-term durability than RF-SN ablation.

Atrioventricular Conduction: Physiology and Autonomic Influences.

Atrioventricular (AV) nodal conduction is decremental and very prone to alterations in autonomic tone. Conduction through the His-Purkinje system (HPS) is via fast channel tissue and typically not that dependent on autonomic perturbations. Applying these principles, when the sinus rate is stable and then heart block suddenly occurs preceded by even a subtle slowing of heart rate, it typically is caused by increased vagal tone, and block occurs in the AV node. Heart block with activity strongly suggests block in the HPS. Enhanced sympathetic tone and reduced vagal tone can facilitate induction of both AV and atrioventricular node reentry.

A Rare Case of Wilson’s Disease in a 17 Years Old Girl

Introduction: Wilson’s disease (WD) is an autosomal recessive disorder involving cellular copper transport. A defect in biliary excretion leads to accumulation of copper in the liver, causing progressive liver injury and cirrhosis. Approximately 1 in 40,000 people have Wilson’s Disease. It affects both men and women equally. Symptoms appear between ages 5 and 35. &#x0D; Case Presentation: This is a case of 17 years old girl came with complained of dysphagia, irritability, breathlessness, weakness in both upper and lower limb at left side for 6 months. She had difficulty in going up and coming down a staircase and in getting up from the squatting position. She could walk with support for the first 6 months of his illness but later, had required crutches. After her admission diagnostic evaluation was done, and in the findings was chest x-ray was done which was normal. ECG showing normal sinus rate and rhythm. Ophthalmology call was done and slit lamp examination was noted which was showing KF ring was present bilaterally. MRI brain suggested symmetrical altered signal intensity lesion in bilateral thalami and lentiform nucleus, midbrain and pons appearing hyper intense on T2/FLAIR sequences in bilateral gangliocapsular region (mainly in putamen) and thalami as well as midbrain and dorsal aspect of pons as described above. A possibility of Wilson’s Disease can be considered, blood test show that Hb was decrease that is -9.7gm%, S.G.O.T was 34.0U/L, S.G.P.T was 32.0U/L, was normal at the time of discharge early ambulation, nutrition, psychological support was given.&#x0D; Therapeutic interventions and outcome: In the present case received syndopa 110/4, BD, orally. Tablet Zinc, OD, orally. Tablet Pan D, OD, orally., inj. Dexamethasone 2 mg I.V, T.D.S., Syrup Sumax, 10ml, BD. Now the patient condition is stable.&#x0D; Conclusion: This presented case of Wilson’s Disease is a rare disease condition. It is an autosomal recessive disease.In this case study, author mainly focus on expert medical management and excellent nursing care which leads to fast recovery of patient. After conversation with patient her response was positive and after nursing management and treatment she was discharged with satisfaction of recovery.

B-PO02-204 EVIDENCE OF TWIN ATRIOVENTRICULAR NODES IN A PATIENT WITH AN SCN5A MUTATION AND STRUCTURALLY NORMAL HEART

Twin atrioventricular (AV) nodes are known to exist in association with complex congenital cardiac lesions. Genetic determinants of AV conduction are poorly understood, although reports have implicated a role of both SCN5A and MYH6 genes. Existence of twin AV nodes in a patient with a structurally normal heart has not previously been reported. We describe a patient with normal cardiac structure demonstrating evidence of twin AV nodes, later found to harbor an SCN5A mutation (D1595N). N/A Evaluation of a 21 week fetus revealed tachycardia, abdominal ascites, and pericardial effusion. Maternal history was significant for pacemaker placement due to intermittent complete heart block. Fetal echocardiogram confirmed supraventricular tachycardia (SVT), which resolved with maternal flecainide therapy. Delivered at term, the infant had a wide-complex bradycardic rhythm with ventricular ectopy concerning for flecainide toxicity. Echocardiogram revealed severely depressed biventricular function with normal intracardiac anatomy and normal abdominal/atrial situs. The rhythm developed into a regular wide-complex tachycardia with no discernable P-waves. Amiodarone resulted in slowing and narrowing of the QRS and emergence of sinus rhythm. By 2 weeks of age, biventricular function normalized. Telemetry revealed sinus rhythm with two distinct QRS morphologies and axes, but with consistent PR intervals and QRS durations. With sinus slowing, accelerated junctional rhythms matching both QRS morphologies were observed suggesting the presence of 2 distinct AV nodes (as opposed to aberrant AV conduction). A single junctional morphology became dominant but with widening of the QRS at higher sinus and junctional rates. Sotalol was initiated with subsequent Holters showing a dominant QRS morphology and a second junctional QRS morphology during sinus pauses. Genetic testing revealed an SCN5A mutation (p.D1595N), later confirmed in the patient’s mother. The presence of twin AV nodes in a living patient with normal cardiac anatomy has not been previously described. Discovery of an SCN5A mutation is an interesting finding, although a mechanistic explanation for its role in AV node formation remains elusive.

The Characteristics and Outcomes of Patients with Heart Failure and Reduced Ejection Fraction: The Eligibility of Novel Heart Failure Medications.

Renin-angiotensin system inhibitors and beta-blockers are the initial treatment of choice for heart failure with reduced ejection fraction (HFrEF), whereas sacubitril/valsartan (SAC/VAL) and ivabradine are considered to second-line therapies. The eligibility of SAC/VAL and ivabradine according to the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA) labels, Taiwan National Health Insurance (TNHI) reimbursement regulations, and European Society of Cardiology (ESC) heart failure (HF) guidelines are diverse, and they may not fulfill the needs of real-world HFrEF patients. Patients hospitalized for HF with left ventricular ejection fraction (LVEF) ≤ 40% were recruited from 21 hospitals in Taiwan between 2013 and 2014. The criteria for SAC/VAL and ivabradine according to the different regulations were applied. Of 1,474 patients, 86.8%, 29.4%, and 9.5% met the EMA/FDA label criteria, TNHI-regulation, and ESC guidelines for SAC/VAL, compared to 47.1%, 37.2%, and 45.6% for ivabradine, respectively. Ineligible reasons for the TNHI regulations included LVEF > 35% (19.9%, for SAC/VAL and ivabradine) and sinus rate < 75 beats per minute (bpm) (29.9%, for ivabradine). Although not meeting the TNHI regulations, patients with LVEF 35-40% had a similar 1-year mortality rate (15.6% vs. 15.8%, p = 0.876) to those with LVEF ≤ 35%, whereas patients with a sinus rate 70-74 bpm had a similar 1-year mortality rate (15.3% vs. 16.1%, p = 0.805) to those with a sinus rate ≥ 75 bpm. Approximately 70% and 63% of TSOC-HFrEF registry patients were ineligible for SAC/VAL and ivabradine, respectively, according to current TNHI regulations. Regardless of the eligibility for novel HFrEF medications, the high incidence of adverse events suggests that all patients should be treated cautiously.

Atrial fibrillation in patients with systolic heart failure: pathophysiology mechanisms and management.

Heart failure (HF) and atrial fibrillation (AF) demonstrate a constantly increasing prevalence during the 21st century worldwide, as a result of the aging population and the successful interventions of the clinical practice in the deterioration of adverse cardiovascular outcomes. HF and AF share common risk factors and pathophysiological mechanisms, creating the base of a constant interrelation. AF impairs systolic and diastolic function, resulting in the increasing incidence of HF, whereas the structural and neurohormonal changes in HF with preserved or reduced ejection fraction increase the possibility of the AF development. The temporal relationship of the development of either condition affects the diagnostic algorithms, the prognosis and the ideal therapeutic strategy that leads to euvolaemia, management of non-cardiovascular comorbidities, control of heart rate or restoration of sinus rate, ventricular synchronization, prevention of sudden death, stroke, embolism, or major bleeding and maintenance of a sustainable quality of life. The indicated treatment for the concomitant HF and AF includes rate or/and rhythm control as well as thromboembolism prophylaxis, while the progress in the understanding of their pathophysiological interdependence and the introduction of the genetic profiling, create new paths in the diagnosis, the prognosis and the prevention of these diseases.

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

Abstract 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 [&amp;lt;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 &amp;lt;0.0001) and attenuation of inducible sinus arrests (maximum pause: 1.2 ± 1.4 vs. 5.5 ± 3.0 s, P &amp;lt;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.

Assessment of arrhythmia mechanism and burden of the infarcted ventricles following remuscularization with pluripotent stem cell-derived cardiomyocyte patches using patient-derived models.

Direct remuscularization with pluripotent stem cell-derived cardiomyocytes (PSC-CMs) seeks to address the onset of heart failure post-myocardial infarction (MI) by treating the persistent muscle deficiency that underlies it. However, direct remuscularization with PSC-CMs could potentially be arrhythmogenic. We investigated two possible mechanisms of arrhythmogenesis-focal vs. re-entrant-arising from direct remuscularization with PSC-CM patches in two personalized, human ventricular computer models of post-MI. Moreover, we developed a principled approach for evaluating arrhythmogenicity of direct remuscularization that factors in the VT propensity of the patient-specific post-MI fibrotic substrate and use it to investigate different conditions of patch remuscularization. Two personalized, human ventricular models of post-MI (P1 and P2) were constructed from late gadolinium enhanced (LGE)-magnetic resonance images (MRIs). In each model, remuscularization with PSC-CM patches was simulated under different treatment conditions that included patch engraftment, patch myofibril orientation, remuscularization site, patch size (thickness and diameter), and patch maturation. To determine arrhythmogenicity of treatment conditions, VT burden of heart models was quantified prior to and after simulated remuscularization and compared. VT burden was quantified based on inducibility (i.e. weighted sum of pacing sites that induced) and severity (i.e. the number of distinct VT morphologies induced). Prior to remuscularization, VT burden was significant in P1 (0.275) and not in P2 (0.0, not VT inducible). We highlight that re-entrant VT mechanisms would dominate over focal mechanisms; spontaneous beats emerging from PSC-CM grafts were always a fraction of resting sinus rate. Moreover, incomplete patch engraftment can be particularly arrhythmogenic, giving rise to particularly aberrant electrical activation and conduction slowing across the PSC-CM patches along with elevated VT burden when compared with complete engraftment. Under conditions of complete patch engraftment, remuscularization was almost always arrhythmogenic in P2 but certain treatment conditions could be anti-arrhythmogenic in P1. Moreover, the remuscularization site was the most important factor affecting VT burden in both P1 and P2. Complete maturation of PSC-CM patches, both ionically and electrotonically, at the appropriate site could completely alleviate VT burden. We identified that re-entrant VT would be the primary VT mechanism in patch remuscularization. To evaluate the arrhythmogenicity of remuscularization, we developed a principled approach that factors in the propensity of the patient-specific fibrotic substrate for VT. We showed that arrhythmogenicity is sensitive to the patient-specific fibrotic substrate and remuscularization site. We demonstrate that targeted remuscularization can be safe in the appropriate individual and holds the potential to non-destructively eliminate VT post-MI in addition to addressing muscle deficiency underlying heart failure progression.

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.