Sinus Node Dysfunction Research Articles

Sinus node dysfunction in children: different aetiologies, similar clinical course in two-centre experience.

This study aims to evaluate the clinical characteristics and outcomes of children diagnosed with sinus node dysfunction. This was a retrospective review of patients diagnosed with sinus node dysfunction in two tertiary paediatric cardiology centres in Turkey from January 2011 to June 2022. In all, 77 patients (50, 64.9% males) were included, with a mean age of 8.2 ± 6.3 years and a mean weight of 28.2 ± 18.8 kg. While age-incompatible bradycardia and pauses were the most common rhythm disturbances, syncope, presyncope, and dizziness (n:33, 43%) were the most frequent initial symptoms. Structural heart disease was present in 58 (75.3%) of the 77 patients, 47 (61%) of whom were congenital. The most commonly associated CHDs were transposition of the great arteries (n:8), atrial septal defect (n:7), and atrioventricular septal defect (n:5). Seven of them also had left atrial isomerism. The remaining 19 patients were isolated. Four patients had SCN5A mutation (two of them were siblings) and two of them had Emery-Dreifuss muscular dystrophy. Although sinus node dysfunction is rare in children, it has been diagnosed with increasing frequency with structural heart disease, especially in patients who have undergone corrective cardiac surgery related to atrial tissue. Since sinus node dysfunction can occur at any time postoperatively, these patients should be kept under constant control. If symptomatic sinus node dysfunction is confirmed, permanent pacing is an effective therapeutic modality.

Familial risk of sinus node dysfunction indicating pacemaker implantation: A nation-wide cohort study.

We aimed to investigate the risk of sinus node dysfunction (SND) indicating cardiac pacing and mortality in first-degree relatives to patients with a pacemaker implanted on this indication and assess the effect of onset-age on disease risk. In this nationwide register-based study we used the Danish civil registration registry to establish family structures and merged data with the Danish National Patient Registry and the Danish Pacemaker and ICD registry containing information on all pacemakers implanted due to SND in Denmark. We followed 6,027,090 individuals born after 1954 for 180,775,041 personyears between 1982-2022 among whom 2.477 pacemakers were implanted due to SND. The adjusted rate ratio (RR) of pacemaker-treated SND was 2.9 (2.4-3.6) for individuals having any father, mother or sibling with a pacemaker implanted on this indication compared with the general population (derived cumulative incidence at the age of 68 years: 0.79% and 0.27%, respectively). This risk was inversely proportional to implantation-age in the index person (≤60 years: RR=5.5 (3.4-9.0)). Overall, mortality was similar between individuals having a father, mother or sibling with SND and the general population, but higher for relatives to index-persons with an early onset (≤60 years: RR=1.22 (1.05-1.41)). First-degree relatives to SND patients are at increased risk of SND with risk being inversely associated with implantation-age in the index person. Mortality in first-degree relatives was comparable to the general population, although subgroup findings suggest an increased mortality among individuals with a family history of earlyonset SND.

Cardiac Implantable Electronic Devices in Cardiac Transplant Patients: A Comprehensive Review

A fraction of patients (approximately 10%) undergoing heart transplantation require permanent pacemaker (PPM) implantation due to sinus node dysfunction or atrioventricular block, occurring either shortly after surgery or later. The incidence of PPM implantation has declined to less than 5% with the introduction of bicaval anastomosis transplantation surgery. Pacing dependency during follow-up varies among recipients. A smaller subset (1.5–3.4%) receives implantable cardioverter-defibrillators (ICDs), but data on their use in transplant recipients are limited, primarily from cohort studies and case series. Sudden cardiac death affects around 10% of transplant recipients, attributed to various nonarrhythmic factors such as acute rejection, late graft failure, and cardiac allograft vasculopathy-induced ischemia. This review offers a comprehensive analysis of the existing data concerning the role of PPMs and ICDs in this population, encompassing leadless PPMs, subcutaneous ICDs, unique considerations, and future directions.

Increased Pacemaker Implantation and Mortality Rates in Relatives of Patients with Early-Onset Sinus Node Dysfunction: Can Genetics Explain All?

Increased Pacemaker Implantation and Mortality Rates in Relatives of Patients with Early-Onset Sinus Node Dysfunction: Can Genetics Explain All?

Abstract 4136518: All-cause mortality for Patients with Preserved Ejection Fraction Heart Failure stratified by B-blocker Therapy and Presence of Permanent Pacemaker.

Background: Beta blockers (BB) and particularly high dose beta blockers might be beneficial for patients with heart failure with preserved ejection fraction (HFpEF), however their use is often limited by commonly coexisting sinus node dysfunction. It is unclear whether the presence of permanent pacemakers (PPM) allows for adequate therapy with BB which in turn confers a mortality benefit. Objective: We sought to evaluate differences in BB treatment between HFpEF patents with and without PPM and evaluate their effect on outpatient mortality. Methods: We identified patients admitted to 1 of 13 Northwell hospitals receiving intravenous diuretics in response to elevated BNP and included in our analysis only those with left ventricular ejection fraction >45%. Status on BB therapy and presence of PPM was assessed at discharge. The vital status of our cohort was identified for the length of the observation period. Results: Of 17,682 patients (42.8% female, 73.5 ± 15.7 years) admitted for HFpEF, 7,910 (44.7%) were discharged on BB, while PPM was present in 397 (2.3%). Treatment with BB was more common among patients with PPM (51.4% vs 48.6%, p=X). There were 1,316 deaths during a follow-up period of 2.4 ± 0.9 years post index admission. Mortality was highest among patients discharged on a BB without PPM and lowest among patients on both BB and PPM (log rank p=0.003) Conclusion: Additional studies are required to assess the complimentary role of pacing and BB therapy in patients with HFpEF.

Abstract 4123563: High Prevalence of Unrecognized Actionable Cardiac Arrhythmias in Patients with Moderate to Severe Chronic Obstructive Pulmonary Disease

Background: Patients with chronic obstructive pulmonary disease (COPD) are at high risk for developing arrhythmias due to hypoxemia, right heart failure and use of beta-agonists inhalers. Symptoms related to arrhythmias can often be masked or confounded by symptoms related to COPD exacerbation and remain undiagnosed. Objective: To identify the incidence of actionable arrhythmias in patients with no prior cardiology follow-up and moderate–severe COPD with continuous monitoring. Methods: An automatic referral for electrophysiology (EP) consult was generated in patients with moderate-severe COPD if they answered yes to one of the following: palpitations, dizziness, abnormal ECG, near syncope. Upon consultation with EP specialist, implantation of loop reorder was discussed (ILR) with the patient. Patients were then monitored for 12 months via remote monitoring. Actionable arrhythmia was defined the arrhythmia that correlated with symptoms triggered by the patient, necessitated adjustment of medications (including initiation of anticoagulation), catheter ablation and implantation of implantable cardiac defibrillator (ICD) or permanent pacemaker (PPM). Results: Out of 62 patients referred 22 (35.5%) agreed to undergo ILR implantation. Of the 22 (50.0% female, 62 ± 9.5 years) patients implanted with an ILR, 15 (68.2%) had an actionable arrhythmia after a mean follow-up of 2.7± .3 months. These included 14 symptomatic events requiring medication adjustment (10 atrial tachycardias, 4 ventricular events), 7 cases of atrial fibrillation (requiring initiation of anticoagulation in all cases and catheter ablation in 1), 1 case of sinus node dysfunction requiring pacemaker implantation, and 1 episodes of sustained ventricular tachycardia requiring ICD implantation. Conclusion: Continuous monitoring had high yield in diagnosing significant arrhythmic events in patients with moderate-severe COPD. Awareness should be raised about the high arrhythmic risk of this population and the role of continuous monitoring should be sought in larger studies.

ATrial arrhythmias in inhEriTed aRrhythmIa Syndromes: results from the TETRIS study.

Little is known about the distribution and clinical course of patients with inherited arrhythmia syndrome (IAS) and concomitant atrial arrhythmias (AAs). 1) to characterize the distribution of AAs in patients with IAS and 2) evaluate the long-term clinical course of these patients. An international multicenter study was performed and involved 28 centers in 16 countries. Inclusion criteria were: 1) IAS and 2) ECG documentation of AAs. The primary endpoint was a composite of sudden cardiac death, sustained VAs or appropriate ICD interventions. Strokes, inappropriate ICD shocks due to AAs, and the occurrence of sinus node dysfunction were assessed. A total of 522 patients with IAS and AAs were included. Most patients were diagnosed with Brugada syndrome (n=355, 68%) and long-QT syndrome (n=93, 18%). The remaining patients (n=71, 14%) presented with short-QT syndrome, early repolarization syndrome (ERS), catecholaminergic polymorphic ventricular tachycardia (CPVT), progressive cardiac conduction diseases, or idiopathic ventricular fibrillation. Atrial fibrillation (AF) was the most prevalent AA (82%), followed by atrial flutter (9%) and atrial tachycardia (9%). AA was the first clinical manifestation of IAS in 52% of patients. More than one type of AAs was documented in 23% of patients. Nine patients (3%) experienced VA before the diagnosis of IAS, due the use of anti-arrhythmic medications taken for the AA. The incidence of the primary endpoint was 1.4% per year, with a twofold increase observed in patients who experienced their first AA before the age of 20 (OR 2.2, p=0.043). This was consistent across the different forms of IAS. Inappropriate ICD shock due to AAs were reported in 2.8% of patients, strokes in 4.4% and sinus node dysfunction in 9.6%. Among patients with IAS and AAs, AA is the first clinical manifestation in about half of the cases, with more than one form of AAs present in one-fourth of the patients. The occurrence of AA earlier in life may be associated with a higher risk of ventricular arrhythmias. The occurrence of stroke and sinus node dysfunction is not-infrequently in this cohort.

Effect of age on clinical impact and mid-term denervation in patients undergoing cardioneuroablation

Cardioneuroablation (CNA) represents a promising therapy for recurrent vasovagal syncope (VVS), extrinsically driven atrioventricular block (AVB) and sinus node dysfunction (SND). However, effectiveness in patients aged 50 and above is not well-established. In this prospective study of patients referred for CNA, we compared syncope and pacemaker implantation free survival, heart rate (HR) variability (HRV) and quality of life between two age groups: group A (< 50 years) and B (≥ 50 years). A total of 50 patients were included (17 Group A and 33 Group B). The etiologies comprised VVS (56%), AVB (22%), and SND (22%). After a median follow-up of 17.0 (12.5–26.0) months, there were no differences of the combined endpoint of syncope or pacemaker implantation free-survival between groups (29.4.% vs. 21.2%; p-log-rank = 0.736). 84% of the entire cohort remained free from syncope, with a better but not significant syncope free survival in the older group (23.5% vs. 12.1%; p-log rank = 0.486). There were no differences in pacemaker implantation rate (A 5.9% vs. B 17.6%; p log-rank = 0.658). Notably, older patients had lower HR values post-procedure compared to younger patients (68.9 ± 13.3 vs. 80.4 ± 16.3 bpm; p = 0.012). Both groups exhibited a decrease in HRV parameters and an improvement in quality of life. In conclusion, CNA has comparable clinical benefits for patients aged 50 and above in terms of syncope or pacemaker implantation free survival and HRV reduction when compared to younger patients.

Case report: Successful implantation of atrial lead in Marshall vein in a patient with sinus node dysfunction.

This case demonstrates that utilizing the vein of Marshall as an alternative option for atrial lead implantation is both safe and effective when encountering challenges during atrial lead implantation.

Terbutaline for Management of Relative Bradycardia Post-Orthotopic Heart Transplant: A Single Center Experience.

Vagal nerve denervation during the heart transplant procedure results in higher resting heart rates in these recipients compared to the general population. Relative bradycardia (RB) is a common and often temporary post-operative complication that can be managed with agents like terbutaline; however, little data exist on the efficacy, safety, and necessity of long-term terbutaline use post-heart transplant. This was a single-center, retrospective, descriptive study conducted at a large academic medical center investigating oral terbutaline use for RB management in heart transplant recipients. Outcomes included time to and reason for terbutaline discontinuation post-transplant, adverse event rates, and permanent pacemaker (PPM) placement rates. In the 229 patients included, the median (IQR) time to terbutaline initiation was 8 (5, 12) days post-heart transplant, with a median (IQR) time to discontinuation of 56 (20, 96) days from the first dose. In most cases, terbutaline was successfully tapered off outpatient due to the resolution of RB. Tachyarrhythmias occurred in 29 (12.7%) patients without long-term sequelae. At 3 months post-transplant, PPM had been placed for chronotropic support in 15 patients (6.6%) with a median time (IQR) to PPM placement of 24 (19, 77) days from transplant. This study's overall low PPM placement rate suggests that early sinus node dysfunction can be treated with pharmacotherapy without committing to a permanent device, and that terbutaline can be used safely in early post-heart transplant recipients. If patients require long-term chronotropic support, the risk-benefit of PPM placement versus continued terbutaline should be considered.

Sinus Node Dysfunction due to Lithium Intoxication.

Sinus Node Dysfunction due to Lithium Intoxication.

Children and Adolescent Patients with Variants in the ATP1A3 -encoded Sodium-Potassium ATPase Alpha-3 Subunit Demonstrate an Impaired QT Response to Bradycardia and Predisposition to Sinus Node Dysfunction.

Alternating hemiplegia of childhood (AHC) is a rare disorder with both neurologic and cardiac manifestations. The ATP1A3-D801N variant is associated with a pathologically short QT interval and risk of ventricular arrhythmia following bradycardia; however, the mechanism of this remains unknown. We investigated the relationship between heart rate (HR), QT, and QTc, hypothesizing that individuals with ATP1A3-D801N have abnormal, impaired shortening of QT and QTc at lower HR leading to arrhythmia predisposition. We performed a retrospective observational study of individuals who underwent clinical evaluation, Holter monitoring, and genetic testing for AHC at Duke University Hospitals. We also compiled a group of healthy individuals as a control cohort. A larger, worldwide cohort of individuals with ATP1A3 -related phenotypes was compiled to investigate sinus node dysfunction. Linear regression analysis was then performed. The cohort consisted of 44 individuals with ATP1A3 -related phenotypes with 81 Holter recordings (52.27% female; mean age at first Holter 8.04 years, range 0.58 - 33 years), compared to 36 healthy individuals with 57 Holter recordings (52.78% female; mean age at first Holter 9.84 years, range 0.08 - 38 years). Individuals with ATP1A3-D801N had reduced prolongation of QT at lower HR, manifest as a significantly lower slope for HR vs QT compared to healthy (P<0.0001). This resulted in a significantly higher slope of the relationship for HR vs QTc compared to healthy (P<0.0001). Individuals with ATP1A3 -related phenotypes and baseline QTc <350 milliseconds (ms) had increased shortening of QT and QTc at lower HR compared to those with normal QTc (P=0.003; P=0.001). Among worldwide cases, 3 out of 131 individuals with ATP1A3 -related phenotypes required device implantation and/or had sinus pauses >4 seconds. Individuals with the ATP1A3-D801N variant exhibit paradoxical shortening of QT and QTc at lower HR, which contributes to an increased risk of arrhythmias during bradycardia. This is exacerbated by an underlying risk of sinus node dysfunction. What is Known:Individuals with ATP1A3-D801N have a short baseline QTc.Two individuals with AHC experienced ventricular fibrillation following bradycardia.What the Study Adds:The QT and QTc shorten to a greater extent at lower heart rate in individuals with ATP1A3-D801N than in healthy individuals. Individuals with ATP1A3 -related phenotypes and QTc <350ms show greater impairment of QT and QTc dynamics than those with normal QTc. There is low prevalence of device implantation and significant sinus pauses in individuals with ATP1A3 -related phenotypes, with a relatively greater prevalence in those with ATP1A3-D801N.

Prognostic parameters predict cardiac events in Brugada syndrome: a meta-analysis

Abstract Background Brugada syndrome (BrS) is recognized as a cause of sudden cardiac death (SCD), ventricular tachycardia or ventricular fibrillation (VT/VF). However, the prognosis varies among the patients with Brugada electrocardiograph (ECG) pattern. Furthermore, there is no prognostic tool to predict the worsening cardiac outcomes in BrS. Objectives Primary outcome was to assess the association between risks including patient history, ECG pattern, electrophysiology study (EPS) findings and cardiac events which is identified as VT/VF or SCD. Method We performed a meta-analysis of prospective and retrospective cohort studies which assessed the risks and cardiac events in patients with BrS. Pooled hazard ratios (HRs) was analyzed by using Random-effect model. Result A total of 27 studies involving 15,990 BrS patients. Of these, 17 were retrospective studies and 10 were prospective studies. In univariate analysis, the risks including male, aborted SCD, QRS duration≥120 msec, fragmented QRS (multiple spikes within the QRS complex in lead V1-V3), late potential (positive terminal filtered QRS complex of signal-averaged ECG), sinus node dysfunction or inducibility of ventricular tachyarrhythmias during EPS associated with a higher risk of cardiac events in BrS. In multivariate analysis, higher risks of cardiac events were associated in BrS patients with history of syncope (HR 2.65, 95% confidence interval (CI): 1.68-4.19, I2 = 54 %, p-value &amp;lt;0.001), family history of SCD (HR 2.64, 95%CI:1.39-5.01, I2 = 0%, p-value = 0.003), prior VF (HR 14.52, 95%CI: 3.36-62.84, I2 = 62%, p-value &amp;lt;0.001), type 1 Brugada ECG pattern (HR 2.07, 95%CI: 1.13-3.79, I2 = 0%, p-value = 0.018), spontaneous type 1 ECG pattern (HR 1.91, 95%CI: 1.01-3.61, I2 = 58%, p-value = 0.046), early repolarization pattern (HR 2.78, 95%CI: 1.9-4.07, I2 = 0%, p-value &amp;lt; 0.001) and history of atrial fibrillation before BrS diagnosis (HR 1.82, 95%CI: 1.03-3.23, I2 = 49%, p-value = 0.039) (Table 1). Conclusion Our findings suggest that patient history, ECG pattern, EPS findings can predict the cardiac events. Introducing a risk prediction model could aid in early management of BrS.

Phenotype groups in atrial cardiomyopathy and their prognosis

Abstract Background Atrial cardiomyopathy (ACM) includes patients with heterogenous demographic characteristics and comorbidities. Defining phenotype groups with similar clinical characteristics is important for the effective treatment of these patients, and for their prognosis and prevention of ACM. Purpose To conduct a cluster analysis that could help us in phenotyping ACM and exploring the clinical complexity of this entity. Methods We performed a hierarchical cluster analysis based on Ward’s Method using 10 clinical binary variables (hypertension, diabetes mellitus, heart failure, obesity, chronic obstructive pulmonary disease, cancer, coronary artery disease, sinus node dysfunction or atrio-ventricular block, implanted pacemaker, and ischemic stroke), identifying the optimal number of clusters. We investigated differences in demographic, laboratory and echocardiographic parameters, and treatment between defined clusters, and assessed the impact of these factors on prognosis. Results Of 724 evaluated consecutive patients with dilated left atrium only 200 met the criteria for advanced atrial cardiomyopathy, defined as severely dilated left atrium with volume index (LAVI) ≥ 48 ml/m2, preserved left ventricular systolic function - ejection fraction ≥ 50%, without an overt valvular or ventricular disease, and were included in the analysis. Mean age of the studied population was 73.91 ± 9.74 years, 58 % of them were women. We identified 4 clusters: cluster 1 (n = 73, 36%) were younger overweight patients with paroxysmal atrial fibrillation (AF); cluster 2 (n = 56, 28%) - old patients with congestive heart failure (CHF) and low body mass index (BMI); cluster 3 (n = 34, 17%)- diabetic patients with obesity and CHF; and cluster 4 (n = 37, 19%) old patients with tachycardia-bradycardia syndrome, implanted pacemakers, and long -standing AF. Over a mean follow up of 20.6 months cluster 2 had the highest mortality rate (28.6%), followed by cluster 3 (20.6%), compared to the lower mortality rate of cluster 1 and 4 (11% and 10.8%, respectively, p=0.047). The presence of heart failure (HR 4.4, CI 1.5 ÷12.7, p=0.006), cancer (HR 3.3, CI 1.6 ÷ 6.9, p=0.002) and greater than moderate tricuspid regurgitation (HR 5.4, CI 2.6 ÷ 11.3, p&amp;lt;0.001) were predictors of poor outcome. Conclusion In patients with advanced atrial cardiomyopathy, four main clusters were identified, differentiated by distinct comorbidities. Both clinical and echocardiographic parameters were found to be associated with an increased risk of mortality.Phenotype clusters of ACMKaplan-Meier curves of clusters

Conduction-System pacing Italian Network Group (C-SING): insights from a Nationwide Multicenter Observational Study

Abstract Background/Introduction Conduction system pacing (CSP), encompassing His bundle pacing (HBP) and left bundle branch area pacing (LBBAP), has gained prominence in treating bradycardia and heart failure in recent years. Despite its increasing utilization, data on real-world adoption of CSP are limited. Purpose The C-SING study aimed at assessing patient characteristics, implant success, procedural details, and safety of CSP when performed in routine clinical practice. Methods Periprocedural data from 27 experienced CSP centers across Italy were collected on patients undergoing CSP implantation for various indications between January 2021 and January 2024. Results The study comprised 1,317 patients (median age 78 years [interquartile range, 71-83], male 66.2%). Leading indications included atrioventricular (AV) block (40.8%), sinus node dysfunction (12.1%), atrial fibrillation with bradycardia (9.7%), AV node ablation (9.5%), and heart failure (12.5%). Pacemakers were implanted in 77.3% of patients, cardiac resynchronization devices in 21.7%, and implantable cardioverter-defibrillators in 1.0%. Stylet-driven and lumenless CSP leads were utilized in 64.7% and 35.3% of procedures, respectively. Final 12-lead ECG assessment revealed LBBAP capture in 88.7% patients, HBP in 8.4% (selective 4.2%, non-selective 4.2%), and no CSP capture in 3.0%, resulting in a 97.0% CSP lead implantation success rate. In patients with LBBAP, predominant capture types were left bundle branch pacing (19.6%), left posterior fascicular pacing (19.2%), and left septal fascicular pacing (14.8%). Comparing HBP to LBBAP, the latter showed shorter procedural time (60 minutes [45-80] vs. 70 minutes [60-95], p=0.003), but similar fluoroscopy time (6.0 minutes [3.3-10.8] vs. 6.1 minutes [4-10], p=0.735). Paced QRS duration was longer in LBBAP (118 ms [105-130]) compared to HBP (110 ms [101-122], p&amp;lt;0.001). LBBAP showed lower capture thresholds (0.6 V [0.5-0.9] @0.4 ms vs. 0.8 V [0.5-1.5] @1.0 ms, p&amp;lt;0.001) and higher R-wave sensing (10.7 mV [8-16] vs. 4.5 mV [2.4-9.9], p&amp;lt;0.001). The rate of periprocedural complications was higher in patients with LBBAP than HBP (7.3% vs. 1.8%, p=0.03), with the most frequent events being intraprocedural perforation into the left ventricular cavity during lead screwing (2.6%) and CSP lead dislodgment before hospital discharge (1.4%). These occurrences necessitated lead repositioning without additional complications. Conclusion CSP demonstrated feasibility as a primary pacing strategy for various indications in a real-world, multicenter setting. LBBAP, more frequently used than HBP, exhibited shorter procedural time and superior acute electrical parameters. LBBAP revealed a higher rate of minor procedural complications than HBP. Further investigations, supported by additional long-term outcome data, are essential to comprehensively assess CSP performance.

Intracardiac leadless pacemaker: long term safety over traditional pacemakers. a systematic review and meta-analysis

Abstract Introduction Leadless pacemaker (LP) is a novel technology designed to reduce lead-related, including pocket infections, associated with traditional pacemakers. LP can be used in patients with high-degree AV block, sinus node dysfunction, and bradycardia with syncope. We conducted a systematic review and meta-analysis to examine the long-term safety of intra-cardiac leadless pacemakers compared with traditional pacemakers. Methods Our protocol was registered in advance on PROSPERO. Studies were eligible if they compared complications, revision, cardiac perforation, infections, and all-cause mortality between patients who received leadless pacemakers versus traditional pacemakers. The systematic search was conducted in five databases (MEDLINE, EMBASE, CENTRAL, Web of Science, Scopus) without restriction. The random-effect model was implemented to calculate pooled odds ratio (OR) with a 95% confidence interval (CI). Also, the Mantel-Haenszel method, Paule-Mandel estimator for tau^2, Q-Profile method for the confidence interval of tau^2 and tau, and Hartung-Knapp adjustment for random effects model methods were used for the prediction of data extracted directly from the curves. ROBINS-I tool was used for the risk of bias assessment, and the certainty of the evidence was evaluated with the GRADE approach. Results Of 6450 studies screened, we identified 21 observational studies of Nanostim and Micra leadless pacemakers. The pooled incidence of complications of leadless versus traditional pacemakers at 1, 6, 12-24 months show the odds are clinically and statistically different (OR=0.66, 95% CI: 0.42–1.02; OR=0.44, 95% CI: 0.22–0.86; OR=0.41, 95% CI: 0.32–0.53 respectively). The pooled incidence of infection rate at 6, 12-24 months is lower in patients with LP (OR=0.37, 95% CI: 0.31–0.44; OR=0.20, 95% CI: 0.00–97.31). The studies comparing all-cause mortality during 6, 12-24 months in leadless versus traditional pacemakers did not show statistically significant differences in these outcomes (OR=1.26, 95% CI: 0.88–1.81; OR=0.86, 95% CI: 0.25–2.92 respectively. Conclusion Our results show that complications and infections occur less frequently in patients with leadless pacemakers than in patients with conventional pacemakers with no difference in all-cause mortality. However, there is a need for high-quality randomized clinical trials and propensity score-matched studies focusing on this clinically relevant question.Complication Forest plotsInfection Forest plots

The importance of heart rate on left ventricular global longitudinal strain in echocardiography: novel insights facilitated by automated deep learning methods

Abstract Background Heart rate (HR) is assumed to influence echocardiographic measurements. Consequently, HR needs to be considered for accurate assessment of cardiac function. Despite left ventricular global longitudinal strain (LV GLS) being recognised as a valuable measure of cardiac function, its normal reference ranges remain confined to patients within a limited range of resting HR. So far, time-consuming manual analyses and high measurement variability have precluded comprehensive assessment of the interplay between HR and LV GLS. Using fully automated GLS measurements provided by novel deep learning (DL) methods, it is now possible to evaluate changes in LV GLS across a wide range of HR. Purpose To improve echocardiographic assessments across a wide range of HR intervals, we aimed to study the influence of controlled HR variations on LV GLS using programmable pacemakers and fully automated DL measurements. Methods Participants with sinus node dysfunction and implanted programmable pacemakers were enrolled. Echocardiographic acquisitions were obtained at baseline HR and during stepwise increments by 10 beats/min, targeting a range from 50 to 140 beats/min. Recordings of cine-loops including 10 cardiac cycles were obtained for the four-chamber, two-chamber, and apical long axis view. LV GLS was measured for all cycles using a fully automated DL method developed by our group, and presented as mean of the three standard apical views for all patients at each HR level. A linear mixed model was used for construction of an overall trendline based on the estimated fixed effects across all 50 patients, stating patient number as the random effect. The correlation between HR and LV GLS was evaluated by a likelihood ratio test. Results Fifty patients were included, 52% females, mean age 68 years (27 to 88 years). All patients had preserved atrioventricular conduction. Resting HR ranged from 50 to 87 beats/min (mean 64 beats/min). At baseline echocardiographic acquisition, most participants were within normal ranges for LV volumes, systolic and diastolic function. A total of about 13,000 cardiac cycles were automatically analysed by the DL method. The overall trend demonstrated a linear relation between increasing HR and decreasing absolute LV GLS (Figure 1). Across HR increments from 50 to 140 beats/min, there was a 32% (22%–42%) reduction in absolute LV GLS, declining from -17.1% to -11.7%. The strong correlation between changes in HR and LV GLS was further supported by a highly significant likelihood ratio test (p-value &amp;lt;0.001). Conclusions There was a reduction of absolute LV GLS with increasing HR. These findings emphasize the importance of integrating HR considerations into clinical echocardiography practice. Moreover, the results highlight that DL methods can unlock substantially richer insights from individual patient data, offering a new pathway towards more personalized and precise cardiac diagnostics.Figure 1

Arrhythmias in adult patients after Rastelli surgery: a single-centre experience.

Rastelli surgery is used for the correction of several CHDs. Although late-onset cardiac arrhythmias have emerged as a major complication after corrective surgeries, there is a paucity of data on arrhythmias after Rastelli surgery. This retrospective cohort study was conducted on patients who had undergone Rastelli surgery and have been followed at the adult CHD clinic at our hospital. A total of 55 patients (36.4% female, age 22.2 ± 6.4 years) were followed for a median period of 24.2 (20.6-31.0) years. Tachyarrhythmias occurred in 21 (38.4 %) patients (n = 15 for atrial tachycardia, 5 for ventricular tachycardia, and 1 for both atrial and ventricular tachycardia). Older age at surgery was significantly associated with the risk of tachyarrhythmias (P = 0.022). Bradyarrhythmia occurred in 12 (21.8%) patients and consisted of perioperative AV block (n = 5), late AV block (n = 1), and sinus node dysfunction (n = 6). Nine (16.4%) patients underwent catheter ablation. The mechanisms of atrial arrhythmias include cavotricuspid isthmus-dependent and surgical scar-dependent intra-atrial reentrant tachycardias. Among the three patients who underwent ablation for ventricular tachycardia, all circuits were dependent on the scar at the base of the right ventricle to pulmonary artery conduit. Median survival free from any event (arrhythmia, death, or heart failure) was 31.6 (28.1-35.1) years after Rastelli surgery. The prevalence of arrhythmias late after Rastelli surgery is substantial and increases in the second decade after surgery. Older age at surgery is associated with a higher prevalence of arrhythmias.

Genetic basis and causal relationship between atrial fibrillation and sinus node dysfunction: Evidence from comprehensive genetic analysis

BackgroundAtrial fibrillation (AF) and sinus node dysfunction (SND) are commonly observed together clinically. However, little is known about the genetic background and causal relationship between the two. MethodsFirstly, we investigated the global and local genetic correlations between AF and SND using LDSC and HESS. Then, we identified shared “Novel SNPs” between AF and SND through two complementary cross-trait meta-analyses and mapped the “pleiotropic genes” behind these SNPs, validated by colocalization analysis. Additionally, we explored the degree of genetic enrichment of SNPs in specific tissues using LDSC-SEG and MAGMA, and identified potential functional genes in tissues using summary data-based Mendelian randomization (SMR). Finally, two-sample Mendelian randomization (TSMR) and multivariable Mendelian randomization (MVMR) were used to explore the causal relationship between AF and SND. ResultsBoth global and local genetic correlation analyses revealed a high positive genetic correlation between AF and SND. HESS identified 9 shared loci, with chr4(q25-q26) and chr11(p11.12-q11) being prominent. Cross-trait meta-analysis and colocalization analysis identified ENPEP and PITX2 as novel pleiotropic genes. MAGMA revealed genetic enrichment of SNPs for AF and SND in the “Heart Left Ventricle” and “Heart Atrial Appendage” tissues, with CEP68 and BEST3 identified as potential functional genes through SMR. MR analysis indicated that AF increases the risk of SND, even after adjusting for confounding factors. ConclusionThis study provides genetic evidence for the increased risk of SND associated with AF, identifying multiple shared risk loci and enriched tissues, and discovering 2 novel pleiotropic genes and 2 new functional genes.

7068 Paraganglioma in Cyanotic Congenital Heart Disease

Abstract Disclosure: R. Lis: None. V. Hamidi: None. Paragangliomas arise from the non-chromaffin cells of the parasympathetic nervous system, which are composed of glomus cells. These function as chemoreceptors in response to hypoxia. Carotid body paragangliomas have been linked to conditions with chronic hypoxia. This was first seen in residents of high altitude locations in a case report presented by Saldana et. al and regression of a paraganglioma with resolution of hypoxia was reported by Gruber et. al. There have been few additional case reports of Paraganglioma in other hypoxic states. We present a rare case of a functional Paraganglioma in a patient with Cyanotic Congenital Heart Disease (CCHD).This is a 19 year old female with a history of CCHD due to double inlet left ventricle and transposition of the great arteries. Soon after birth, she had a fontan procedure. She subsequently developed fontan associated liver disease as well as chronic kidney disease, hypertension, sinus node dysfunction, and complete heart block. Her baseline oxygen saturation was 78-85%. Her heart rate was 40-49 beats per minute with upcoming plans for pacemaker placement. Her blood pressure ranged 90/50 to 150/80 mmHg on Amlodipine 5 mg and Lisinopril 2.5 mg. She routinely received abdominal imaging to monitor her liver disease. A liver MRI incidentally revealed a retroperitoneal mass concerning for a paraganglioma. Serum Normetanephrines were found to be 26.60 nmol/L (reference range less than 0.89). 24 hr Urine Norepinephrine was 1,187 ug/d (reference range 14-20). Further imaging was negative for additional sites of disease. Given her complete heart block, she was started on alpha blockade only prior to pacemaker placement. After the pacemaker was placed, she was started on beta blockade and underwent surgical resection of her paraganglioma. The pathology confirmed paraganglioma and mutation testing was negative for germline mutations including SDH, VHL, RET, NF1 mutations. Paragangliomas in patients with CCHD have been scarcely described in the literature given the rarity of both of these conditions. However, there is a relatively increased incidence of paragangliomas in the CCHD population due to chronic hypoxia triggering the hypoxia pathway. EPAS1 mutated HIF2alpha is often found to be the culprit in these patients. In addition, case reports have often described these patients to either be asymptomatic or have potential symptoms masked by their cardiac disease. Therefore, CCHD patients are at increased risk for paragangliomas and warrant additional awareness and regular screening. Screening has been proposed to start after 10 years of hypoxia in a case review by Agarwal et. al. as paraganglioma incidence in CCHD populations has not been seen before age 11. Incidence of recurrence is not yet widely studied, but significant concern for recurrence is warranted if the etiology of hypoxia is not reversed. Presentation: 6/3/2024