Sinus Node Dysfunction Research Articles

Medetomidine/midazolam/fentanyl narcosis alters cardiac autonomic tone leading to conduction disorders and arrhythmias in mice

Arrhythmias are critical contributors to cardiovascular morbidity and mortality. Therapies are mainly symptomatic and often insufficient, emphasizing the need for basic research to unveil the mechanisms underlying arrhythmias and to enable better and ideally causal therapies. In translational approaches, mice are commonly used to study arrhythmia mechanisms in vivo. Experimental electrophysiology studies in mice are performed under anesthesia with medetomidine/midazolam/fentanyl (MMF) and isoflurane/fentanyl (IF) as commonly used regimens. Despite evidence of adverse effects of individual components on cardiac function, few data are available regarding the specific effects of these regimens on cardiac electrophysiology in mice. Here we present a study investigating the effects of MMF and IF narcosis on cardiac electrophysiology in vivo in C57BL/6N wild-type mice. Telemetry transmitters were implanted in a group of mice, which served as controls for baseline parameters without narcosis. In two other groups of mice, electrocardiogram and invasive electrophysiology studies were performed under narcosis (with either MMF or IF). Basic electrocardiogram parameters, heart rate variability parameters, sinus node and atrioventricular node function, and susceptibility to arrhythmias were assessed. Experimental data suggest a remarkable influence of MMF on cardiac electrophysiology compared with IF and awake animals. While IF only moderately reduced heart rate, MMF led to significant bradycardia, spontaneous arrhythmias, heart rate variability alterations as well as sinus and AV node dysfunction, and increased inducibility of ventricular arrhythmias. On the basis of these observed effects, we suggest avoiding MMF in mice, specifically when studying cardiac electrophysiology, but also whenever a regular heartbeat is required for reliable results, such as in heart failure or imaging research.

Echocardiographic Evaluation of His Bundle Pacing in Patients with Prolonged PR Intervals.

Patients with PR intervals >240ms have atrio-ventricular (AV) dyssynchrony, which can increase risk of atrial fibrillation and all-cause mortality. When requiring pacing, long AV delays (AVDs) have been programmed to avoid ventricular dyssychrony. His bundle pacing (HBP) may provide improved AV synchrony in patients with prolonged PR. 10 patients with sinus node dysfunction and prolonged PR who received HBP were studied. Real-time echocardiographic was performed with 3 pacemaker modes (RV septal, non-selective HBP, and selective HBP) using the following pacemaker settings: control (no ventricular pacing), pacing with AVD of 180ms, 150ms, 120ms, 100ms, and 70ms. Echocardiographic Doppler measurements: EA/RR, >40% = AV synchrony; E/e', <8 = normal left atrial pressure; pulmonic-to-aortic pre-ejection time difference, <40ms = interventricular synchrony; septal-to-lateral wall activation time difference, <56ms = intraventricular synchrony; and LVOT VTI. Unpaired T test was used to evaluate for significance. Exclusion criteria: persistent atrial fibrillation, second-degree AV block. Compared to control programming, HBP showed a 31.5% increase in EA/RR time, a decrease in E/e' of 26.9%, and an increase in the LVOT VTI of 21.3%. Compared to RV septal pacing, there was a similar increase in LVOT VTI. These findings met statistical significance and were considered optimal based on Doppler echocardiography findings primarily at AVDs of 150ms and 120ms. Comparisons between selective and non-selective pacing were not significantly different. Compared to controls and RV septal pacing, physiologic His bundle pacing was shown to increase markers of AV synchrony and LV stroke volume while maintaining ventricular synchrony.

Sinus node dysfunction and related permanent pacemaker implantation after major cardiac surgeries, systematic review, and meta-analysis.

There is no concise evidence or clinical guidelines regarding the incidence of sinus node dysfunction (SND) and permanent pacemaker (PPM) implantation following cardiac surgeries and their management approaches. We aim to systematically review current evidence on the prevalence of SND, PPM implantation concerning it, and its risk factors in patients undergoing cardiac surgery. Four electronic databases (Cochrane Library, Medline, SCOPUS, and Web of Science) were systematically searched for articles regarding SND after cardiovascular surgeries and reviewed by two independent researchers, and a third review in case of discrepancies. Using the random-effects model, a proportion meta-analysis was performed on data regarding PPM implantation. Subgroup analysis was performed for different interventions, and the possible effect of different covariates was evaluated using meta-regression. From the initial 2012 unique records, 87 were included in the study, and results were extracted. Pooled data from 38,519 patients indicated that the overall prevalence of PPM implantation due to SND after cardiac surgery was 2.87% (95% CI [2.09; 3.76]). The incidence of PPM implantation in the first post-surgical month was 2.707% (95% CI [1.657; 3.952]). Among the four main intervention groups, including valve, maze, valve-maze, and combined surgeries, maze surgery was associated with the highest prevalence (4.93%; CI [3.24; 6.92]). The pooled prevalence of SND among studies was 13.71% (95% CI [8.13; 20.33]). No significant relationship was observed between PPM implantation and age, gender, cardiopulmonary bypass time, or aortic cross-clamp time. Based on the present report, patients undergoing the maze and maze-valve procedures are at higher risk of post-op SND, whereas lone valve surgery had the lowest prevalence of PPM implantation. PROSPERO (CRD42022341896).

Brugada Syndrome: 30 Years of Scientific Ventures.

Thirty years ago, a distinctly new clinical-electrocardiographic syndrome was described, today known as Brugada Syndrome (BrS). Typical treatment for this type of syndrome is electrocardiography with ST-segment elevation in the direct precordial derivations. The clinical presentation of the disease is highly variable: the patients can remain completely asymptomatic, but they can also develop episodes of syncope, atrial fibrillation (AF), sinus node dysfunction (SNF), conduction disorders, asystole, and ventricular fibrillation (VF). This disease is caused by mutations in the genes responsible for the potential action of cardiac cells. The most commonly involved gene is SCN5A, which controls the structure and function of the heart's sodium channel. The description of this new syndrome has shown highly positive implications in all fields of medicine.

Association of late tricuspid regurgitation progression and intracardiac lead types in patients after primary implantation of cardiac electronic devices

Aim. To evaluate the factors and degree of progression of tricuspid regurgitation (TR) depending on the type of implanted electrode in patients after primary implantation of a cardiac implantable electronic device (CIED) in the late postoperative period.Methods. Case histories of 674 patients who underwent primary implantation of an implantable cardioverterdefibrillator (ICD) for the secondary prevention of sudden cardiac death for the period from 2009 to 2019 were analyzed and 75 case histories were selected. Using similar criteria, a comparison group was selected, who were implanted with a permanent pacemaker (PM) for sinus node dysfunction. For maximum comparability of the main and reference groups, pseudo-randomization was used using the nearest neighbor search method; 68 pairs were formed, comparable in terms of the main factors. Multiple logistic regression was used to analyze the predictors of progression of TR in the postoperative period.Results. In the preoperative period in the ICD group, 34 patients (50%) had a mild degree of TR, moderate and severe TR occurred in an equal number of cases 2 patients (2.9%) each. In the PM group, mild TR was detected in 24 cases (35.3%), moderate in 2.9% (n=2) of cases, respectively. In the postoperative period, predominantly mild TR was determined in both groups (in the ICD group in 67.6% (n=46), in the PM group in 48 patients (70.6%)).In the analysis of the general group of patients with implanted CIEDs (n=136), in the late postoperative period, an increase in the volume of both atria and the degree of TR was revealed. Left ventricular ejection fraction and end-diastolic volume didn’t have significant dynamics. All echocardiographic data obtained in the postoperative period were within the normal range.According to the results of multiple logistic regression, a history of coronary heart disease (CHD) has the greatest predictive power (hazard ratio 4.170; 95% confidence interval 1.751-9.933, p=0.001).Conclusion. TR in patients after primary implantation of a CIED in the late postoperative period progresses slightly, regardless of the type of right ventricular electrode. A long history of CHD is associated with the greatest risk of progression to tricuspid valve insufficiency.

Pediatric Epicardial Devices: Early and Midterm Outcomes.

Lead performance is suboptimal in young patients and a main cause of device system failure. Our objective was to assess early and midterm outcomes after epicardial device implantation in a contemporary pediatric cohort. A total of 116 consecutive pediatric patients underwent 137 epicardial device implantations from 2010 to 2019. Forty pacemakers and 97 implantable cardioverter defibrillators (ICDs) were implanted. Lead failure was defined as leads repaired, replaced, or abandoned due to fracture, dislodgement, or dysfunction. Freedom from device system failure was determined using Kaplan-Meier analysis. Mean age at implantation was 10 ± 5 years, 46 (34%) were younger than 8 years old, 41 (30%) had prior cardiac surgery, and 38 (28%) had prior devices. Main indications were acquired heart block (17/40 [43%]), sinus node dysfunction (14/40 [35%]), and congenital heart block (7/40 [18%]) for pacemakers, and hypertrophic cardiomyopathy (46/97 [47%]), long QT syndrome (31/97 [32%]), and ventricular arrhythmia (17/97 [18%]) for ICDs. There were no early deaths. Three-year freedom from device system failure was 80% (95% CI 73%, 88%) for all patients and 88% (95% CI 79%, 99%) for patients <8 years old. Device system failure causes included lead fracture (20/34 [59%]), lead dysfunction (5/34 [15%]), lead dislodgement (5/34 [15%]), infection (3/34 [9%]), and pericarditis (1/34 [3%]). Reintervention was required in 26/34 (76%) device system failures. Epicardial device implantation is safe, shows acceptable midterm outcomes in children, and is an effective option in patients younger than 8 years old. Close device surveillance continues to be essential to detect lead failure early and ensure timely reintervention.

Mitochondrial Dysfunction in Cardiac Arrhythmias.

Electrophysiological and structural disruptions in cardiac arrhythmias are closely related to mitochondrial dysfunction. Mitochondria are an organelle generating ATP, thereby satisfying the energy demand of the incessant electrical activity in the heart. In arrhythmias, the homeostatic supply-demand relationship is impaired, which is often accompanied by progressive mitochondrial dysfunction leading to reduced ATP production and elevated reactive oxidative species generation. Furthermore, ion homeostasis, membrane excitability, and cardiac structure can be disrupted through pathological changes in gap junctions and inflammatory signaling, which results in impaired cardiac electrical homeostasis. Herein, we review the electrical and molecular mechanisms of cardiac arrhythmias, with a particular focus on mitochondrial dysfunction in ionic regulation and gap junction action. We provide an update on inherited and acquired mitochondrial dysfunction to explore the pathophysiology of different types of arrhythmias. In addition, we highlight the role of mitochondria in bradyarrhythmia, including sinus node dysfunction and atrioventricular node dysfunction. Finally, we discuss how confounding factors, such as aging, gut microbiome, cardiac reperfusion injury, and electrical stimulation, modulate mitochondrial function and cause tachyarrhythmia.

Prevalence and Prognostic Significance of Bradyarrhythmias in Patients Screened for Atrial Fibrillation vs Usual Care

There is increasing interest in heart rhythm monitoring and technologies to detect subclinical atrial fibrillation (AF), which may lead to incidental diagnosis of bradyarrhythmias. To assess bradyarrhythmia prevalence and prognostic significance in persons screened for AF using implantable loop recorder (ILR) compared with unscreened persons. This was a post hoc analysis of the Implantable Loop Recorder Detection of Atrial Fibrillation to Prevent Stroke (LOOP) randomized clinical trial, which took place in 4 sites in Denmark. Participants were 70 years or older without known AF but diagnosed with at least 1 of the following: hypertension, diabetes, heart failure, or prior stroke. Participants were recruited by letter invitation between January 31, 2014, and May 17, 2016. The median (IQR) follow-up period was 65 (59-70) months. Analysis took place between February and June 2022. ILR screening for AF with treatment of any bradyarrhythmia left to the discretion of the treating physician (ILR group) vs usual care (control group). Adjudicated bradyarrhythmia episodes, pacemaker implantation, syncope, and sudden cardiovascular death. A total of 6004 participants were randomized (mean [SD] age, 75 [4.1] years; 2837 [47.3%] female; 5444 [90.7%] with hypertension; 1224 [20.4%] with prior syncope), 4503 to control and 1501 to ILR. Bradyarrhythmia was diagnosed in 172 participants (3.8%) in the control group vs 312 participants (20.8%) in the ILR group (hazard ratio [HR], 6.21 [95% CI, 5.15-7.48]; P < .001), and these were asymptomatic in 41 participants (23.8%) vs 249 participants (79.8%), respectively. The most common bradyarrhythmia was sinus node dysfunction followed by high-grade atrioventricular block. Risk factors for bradyarrhythmia included higher age, male sex, and prior syncope. A pacemaker was implanted in 132 participants (2.9%) vs 67 (4.5%) (HR, 1.53 [95% CI, 1.14-2.06]; P < .001), syncope occurred in 120 (2.7%) vs 33 (2.2%) (HR, 0.83 [95% CI, 0.56-1.22]; P = .34), and sudden cardiovascular death occurred in 49 (1.1%) vs 18 (1.2%) (HR, 1.11 [95% CI, 0.64-1.90]; P = .71) in the control and ILR groups, respectively. Bradyarrhythmias were associated with subsequent syncope, cardiovascular death, and all-cause death, with no interaction between bradyarrhythmia and randomization group. More than 1 in 5 persons older than 70 years with cardiovascular risk factors can be diagnosed with bradyarrhythmias when long-term continous monitoring for AF is applied. In this study, ILR screening led to a 6-fold increase in bradyarrhythmia diagnoses and a significant increase in pacemaker implantations compared with usual care but no change in the risk of syncope or sudden death.

Selection of patients with symptomatic vagal-induced sinus node dysfunction: Who will be the best candidate for cardioneuroablation?

Sinus node dysfunction is a multifaceted disorder with variable manifestations, the prevalence of which increases with age. In a specific group of patients, excessive vagal activity may be the sole cause for this condition. These patients are characterized as having recurrent daytime symptoms attributed to bradyarrhythmia, no evidence of organic sinus node lesions, cardiac vagal overactivation, and are non-elderly. For sinus node dysfunction patients, a permanent pacemaker implantation appears to be the ultimate solution, although it is not an etiological treatment. Cardioneuroablation is a promising emerging therapy that can fundamentally eliminate symptoms in a highly selective sub-set of sinus node dysfunction patients by cardiac vagal nerve denervation. Denervation with ablation for vagal-induced sinus node dysfunction can effectively improve sinus bradycardia and reduce syncope. To date, guidelines for selection of suitable candidates for cardioneuroablation remain lacking. The primary objective of this study was to distinguish the nature of abnormal sinus node function and to find methods for quantifying vagal tone. Clear selection criteria could help physicians in identification of patients with autonomic imbalance, thereby maximizing patient benefits and the success rate of cardioneuroablations.

Super-resolved SIM imaging revealed hierarchical organization of the ryanodine receptor network in 3 dimensions in rabbit sinoatrial node cells.

The heartbeat is initiated by specialized sinoatrial node cells (SANCs). The rate of the heartbeat is regulated by Ca released from the sarcoplasmic reticulum (SR) via ryanodine receptors (RyRs) interacting with voltage and Ca-dependent membrane ion currents in SANCs. The released Ca takes the form of localized Ca releases (LCRs) that propagate for limited distances in wave-like manner. A computational model of SANCs, previously developed in our laboratory, simulates LCR synchronization mechanism as hierarchical clustering of surface RyRs based on confocal microscopy imaging data obtained in tangential sections of SANCs. The true detailed distribution of RyR clusters in 3D, however, remains unknown. Here, we applied a series of new computational approaches to experimental data obtained by super-resolved structured illumination microscopy in rabbit SANCs, in which RyRs were labeled by specific antibodies. Our approach consists of automated segmentation of RyR clusters with globally optimal detection and segmentation of objects with constant internal intensity distribution, followed by object-based colocalization analysis in 3D. Results are further refined with watershed transformations and computational geometry. Examinations of the images have revealed a hierarchical architecture of RyR network (positions and sizes of submembrane RyR clusters). After constructing a mathematical convex hull around the cell using RyR clusters as nodes, clusters were grouped based on their volume. The distribution of RyR clusters exhibited a wide range of sizes from 0.75 × 10−3 µm3 to 0.50 µm3 and cluster histograms followed a Poisson-like distribution. These new data have been incorporated in a new, realistic 3D model of SANC, in which heterogeneous RyR clusters facilitate LCR propagation. Impairment of the complex, hierarchical structure of RyR clusters may lead to sinus node dysfunction in aging and disease.

352 - Clinical profile of 110 young patients with sinus node dysfunction who required a pacemaker

352 - Clinical profile of 110 young patients with sinus node dysfunction who required a pacemaker

Surgical treatment of paroxysmal atrial fibrillation concomitant to coronary artery bypass grafting: pulmonary vein isolation or maze V?

Highlights. Maze V significantly reduces the recurrence of AF compared to bipolar RFA for PVI in the short and mid-term period.Aim. To assess the effectiveness and safety of pulmonary vein isolation (PVI) in comparison with Maze V for treating paroxysmal atrial fibrillation (AF) concomitant to coronary artery bypass grafting (CABG).Methods. Medical records of 139 patients with coronary artery disease and concomitant paroxysmal AF were retrospectively analyzed. All patients were divided into two groups: Group 1 patients (n = 71) underwent CABG + bipolar radiofrequency ablation for PVI, and Group 2 patients (n = 68) underwent Maze V + CABG. Propensity score-matched (PSM) analysis with a 1:1 nearest-neighbor matching was done. 30 patients were selected from each group. The exclusion criteria were as follows: emergent CABG, concomitant valvular heart disease, non-paroxysmal AF, decompensation of chronic diseases, and cancer. On-pump CABG was performed at normothermia with warm blood hyperkalemia cardioplegia. RFA for PVI and Maze V were performed before CABG under parallel perfusion without aortic cross-clamping. The primary and secondary endpoints included recurrent AF/atrial flutter, sinus rhythm at discharge and in the long-term period, permanent pacemaker implantation, major cardiovascular and cerebrovascular events.Results. After the PSM analysis, the CABG+Maze V group and CABG+RFA for PVI differed significantly in the duration of surgery (330 [310; 375] vs. 255 [225; 270] min, p = 0.0001), cardiopulmonary bypass time (131 [113; 144] min vs. 89 [74; 98] min, p = 0.0001), duration of AF treatment (53 [44; 59] min vs. 10 [9; 12] min, p = 0.0001). The structure and rate of complications in both groups were comparable. There were no in-patient deaths. Recurrent AF/atrial flutter significantly reduced in the CABG+Maze V group compared to the CABG+RFA for PVI group (13.3% vs. 33.3%, respectively; p = 0.044). Sinus rhythm was restored in all cases. The rate of transient sinus node dysfunction (no more than 5 days) was 6.7% in the Group 1 and 16.6% in the Group 2. The difference did not reach statistical significance (p = 0.128). The 12-months cumulative freedom from AF/atrial flutter without antiarrhythmic drug therapy was significantly higher in the CABG+Maze V group compared to the CABG+RFA for PVI group (97% vs. 83.5%, respectively; p = 0.020). The freedom from MACE in both groups was 96.7%.Conclusion. Maze V for treating concomitant paroxysmal AF prolonged the duration of cardiopulmonary bypass and the surgery itself, but did not affect the postoperative period, indicating its safety and effectiveness. Maze V procedure concomitant to CABG significantly reduced the recurrence of AF compared to RFA for PVI both in the short- and mid-term period. Thus, it is reasonable to perform Maze V+CABG in patients with paroxysmal AF and a high risk of disease progression.

Pacing Induced Cardiomyopathy: Diagnosis and Management

Permanent pacemaker is the mainstay treatment indicated for bradycardia caused by sinus node dysfunction. However, heart failure may appear in patients with chronic right ventricle pacing, this is known as Pacing-Induced Cardiomyopathy (PICM). There is no internationally accepted definition for diagnosis of PICM. Studies show the prevalence of PICM is 9% in the first year and increases in proportion to the duration of PPM implantation, but varies widely according to diagnostic criteria used. PICM causes a higher all-cause death, hospital admission, and cardiac death. Therefore, detecting risk factors may be an important part of the prevention and early treatment of PICM. Once PICM develops, several therapy options are available but Cardiac Resynchronization Therapy with biventricular Pacemaker is currently the forefront of treatment. But insight into other more novel therapeutic options such as; His bundle pacing and Left Bundle Branch Pacing shows promising results as an alternative treatment option in the near future.

Incidence and predictors of pacemaker implantation at follow-up after reversible high-degree sinus node dysfunction or atrioventricular block

Incidence and predictors of pacemaker implantation at follow-up after reversible high-degree sinus node dysfunction or atrioventricular block

Safety and Efficacy of Right Axillary Thoracotomy for Repair of Congenital Heart Defects in Children.

Minimally invasive repair of congenital heart defects in children has not gained wide popularity yet compared to minimally invasive approaches in adults. We sought to review our experience with this approach in children. This study included a total of 37 children (24 girls, 64.9%) with a mean age of 6.5 ± 5.1 years, who underwent vertical axillary right minithoracotomy for repair of a variety of congenital heart defects between May 2020 and June 2022. The mean weight of these children was 25.66 ± 18.3 kg. Trisomy 21 syndrome was present in 3 patients (8.1%). The most common congenital heart defects that were repaired via this approach were atrial septal defects (secundum in 11 patients, 29.7%; primum in 5, 13.5%; and unroofed coronary sinus in 1, 2.7%). Twelve patients (32.4%) underwent repair of partial anomalous pulmonary venous connections with or without sinus venosus defects, while 4 patients (10.8%) underwent closure of membranous ventricular septal defects. Mitral valve repair, resection of cor triatriatum dexter, epicardial pacemaker placement, and myxoma resection occurred in 1 patient (2.7%) each. No early mortality or reoperations. All patients were extubated in the operating room, and the mean length of hospital stay was 3.3 ± 2.04 days. Follow-up was complete (mean 7 ± 5 months). No late mortality or reoperations. One patient required epicardial pacemaker placement due to sinus node dysfunction 5 months after surgery. Vertical axillary right thoracotomy is a cosmetically superior approach that is safe and effective for repair of a variety of congenital heart defects in children.

An overview of brady dysrhythmias in the emergency department

Bradyarrhythmias, which include physiological and pathological disorders such as sinus node dysfunction and atrioventricular conduction disturbances are frequent clinical findings in the emergency department. Although some benign bradyarrhythmias do not need treatment, acute unstable bradycardia can lead to cardiac arrest. A thorough history and physical examination should cover potential causes of sinoatrial node dysfunction or atrioventricular block in patients with confirmed or suspected bradycardia. Based on the severity of the symptoms, the underlying causes, the presence of possibly reversible causes, the presence of negative indications, and the danger of asystole progression, bradyarrhythmias are managed. Bradyarrhythmias that are unstable or symptomatic are treated with medication and/or pacing. Bradycardia is described as an adult heart rate of less than 60 beats per minute. Syncope, presyncope, momentary light-headedness or dizziness, exhaustion, dyspnea with exertion, heart failure symptoms, or disorientation brought on by cerebral hypoperfusion are typical signs of bradycardia. Atropine plays a significant role in the management of bradyarrhythmias because it counteracts the impact of the parasympathetic vagus nerve system, which can cause an increase in heart rate. Atropine administration is indicated in cases with vagus-mediated asystole, obstructions in the atrioventricular node, and sinus bradycardia. Installation of temporary pacemaker, permanent pacemaker is also among the effective management strategies of the bradyarrythmias. Diagnosis and management of bradyarrythmias in emergency department is of utmost importance since it can prevent morbidity and mortality. The purpose of this research is to review the available information about an overview of bradydysrhythmias in the emergency department.

Atrioventricular dyssynchrony in patients with permanent pacemaker due to sinus node dysfunction and first-degree atrioventricular block: does the long PR syndrome exist?

Atrioventricular dyssynchrony in patients with permanent pacemaker due to sinus node dysfunction and first-degree atrioventricular block: does the long PR syndrome exist?

Results of Using Various Conduction System Pacing Options in Patients with Bradyarrhythmia

Chronic right ventricular myocardial pacing causes an asynchronous pattern of left ventricular activation, reduces left ventricular ejection fraction (LVEF), and may be associated with worsening of clinical outcomes in the long term. Although with the emergence of algorithms that minimize ventricular pacing it became possible to reduce the percentage of paced complexes in patients with sinus node dysfunction, permanent ventricular pacing is still inevitable in patients with high-degree atrioventricular (AV) block. The use of permanent conduction system pacing is a promising method for preserving the physiological activation of the ventricular myocardium and preventing the development of heart failure due to ventricular dyssynchrony.&#x0D; The aim. To analyze the immediate and long-term results of the use of conduction system pacing in patients with indications for permanent ventricular pacing.&#x0D; Materials and methods. This study included 18 patients with indications for permanentventricular pacing who were operated at the National Amosov Institute of Cardiovascular Surgery of the National Academy of Medical Sciences of Ukraine in the period from 01/01/2013 to 12/31/2022, in whom permanent conduction system pacing was used. There were 17 patients with bradyarrhythmias, of these 16 (88%) suffered from high-degree AV block (including 1 patient with Frederick’s syndrome and 1 (5%) patient with atrial ϐibrillation with slow ventricular response) and 1 (5%) patient with ischemic cardiomyopathy with left bundle branch block and ϐirstdegree AV block with indications for cardiac resynchronization therapy. The mean age of the patients was 55 ± 16 years (8 men, 10 women), LVEF at the time of the intervention was 56.42 ± 9.13 %, end diastolic volume 130.2 ± 23.8 ml, end systolic volume 55.1 ± 17.7 ml, diameter of the left atrium 4.01 ± 0.6 cm. The average QRS width before implantation was 116.5 ± 27.7 ms. In 6 (33%) patients, a special delivery system (С304-L69, Medtronic in 1 patient [5%], C315HIS in 5 [27%] patients) and 4.1F active ϐixation lead Medtronic 3830 Select Secure (69 or 74 cm) were used; in other cases (66%) standard 6F leads with active ϐixation and a lumen for a stylet without a delivery system were used.&#x0D; Results. The average follow-up period after implantation of pacemaker was 36.35 ± 29.65 months. During the observation period, LVEF was 57.07 ± 5.38 %, end diastolic volume111.5 ± 18.09 ml, end systolic volume 49.5 ± 13.4 ml, diameter of the left ventricle 3.9 ± 0.5 cm. The mean duration of paced QRS was 119.1 ± 10.09 ms. In 6 patients (33%), it was possible to demonstrate a change in the QRS width when the amplitude of ventricular stimulation was reduced, with 2 variants of transitions: 1) 4 (22%) patients with a transition from non-selective His bundle pacing (NSHBP) to selective His bundle pacing (SHBP), in 2 (11%) of these patients with a transition from SHBP with correction of right bundle branch block (RBBB) to SHBP without correction of RBBB, and then loss of capture of the myocardium of the ventricles; 2) 2 patients (11%) with a transition from NSHBP to myocardial septal ventricular pacing and further with a decrease in amplitude to the loss of capture of the myocardium of the ventricles. One (5%) patient with complete heart block had permanent non-selective left bundle branch area pacing. The other 11 (61%) patients met the criteria for parahisian pacing without visible transitions with a change in the amplitude of ventricular pacing. The average global longitudinal strain was -17.6 ± 2.7 %. The average interval from the stimulus to the peak of the R-wave in lead V6, which indicated the time of left ventricular activation, was 73.2 ± 8.7 ms. Pacing parameters were standardly set according to the primary indications, but with correction of the amplitude of ventricular stimulation relative to the thresholds of pacing of the conduction system. AV delay was corrected for the latency from the stimulus to the onset of the QRS in SHBP or for the duration of the “pseudodelta” wave in NSHBP which in both cases was the duration of the H-V interval. There were no complications in the acute or long-term postoperative period.&#x0D; Conclusions. Conduction system pacing is a challenge in the practice of cardiologist for treating life-threatening bradyarrhythmias and heart failure, but at the same time it is a safe method that provides physiological electrical and mechanical activation of the myocardium of the ventricles, that allows to effectively avoid the consequences of dyssynchrony due to permanent myocardial ventricular pacing.

Sinus node dysfunction: current understanding and future directions.

The sinoatrial node (SAN) is the primary pacemaker of the heart. Normal SAN function is crucial in maintaining proper cardiac rhythm and contraction. Sinus node dysfunction (SND) is due to abnormalities within the SAN, which can affect the heartbeat frequency, regularity, and the propagation of electrical pulses through the cardiac conduction system. As a result, SND often increases the risk of cardiac arrhythmias. SND is most commonly seen as a disease of the elderly given the role of degenerative fibrosis as well as other age-dependent changes in its pathogenesis. Despite the prevalence of SND, current treatment is limited to pacemaker implantation, which is associated with substantial medical costs and complications. Emerging evidence has identified various genetic abnormalities that can cause SND, shedding light on the molecular underpinnings of SND. Identification of these molecular mechanisms and pathways implicated in the pathogenesis of SND is hoped to identify novel therapeutic targets for the development of more effective therapies for this disease. In this review article, we examine the anatomy of the SAN and the pathophysiology and epidemiology of SND. We then discuss in detail the most common genetic mutations correlated with SND and provide our perspectives on future research and therapeutic opportunities in this field.

Pathological and Comprehensive Genetic Investigation of Autopsy Cases of Idiopathic Bradyarrhythmia.

Idiopathic bradyarrhythmia is considered to be due to pathological degeneration of the cardiac conduction system (CCS) during aging. There appears to have been no comprehensive genetic investigations in patients with idiopathic bradyarrhythmia. Ten autopsy cases with advanced bradyarrhythmia (6 men and 4 women; age: 70-94 years, 81.5±6.9 years; 5 cases each of sinus node dysfunction [SND] and complete atrioventricular block [CAVB]) were genetically investigated by using whole-exome sequencing. Morphometric analysis of the CCS was performed with sex-, age- and comorbidity-matched control cases. As a result, severe loss of nodal cells and distal atrioventricular conduction system were found in SND and CAVB, respectively. However, the conduction tissue loss was not significant in either the atrioventricular node or the proximal bundle of His in CAVB cases. A total of 13 heterozygous potential variants were found in 3 CAVB and 2 SND cases. Of these 13 variants, 4 were missense in the known progressive cardiac conduction disease-related genes: GATA4 and RYR2. In the remaining 9 variants, 5 were loss-of-function mutation with highly possible pathogenicity. In addition to degenerative changes of selectively vulnerable areas in the heart during advancing age, the vulnerability of the CCS, which may be associated with "rare variants of small effect," may also be a contributing factor to the degeneration of CCS, leading to "idiopathic" bradyarrhythmia.