Sinus node dysfunction and atrial fibrillation-Relationships, clinical phenotypes, new mechanisms, and treatment approaches.

Although the anatomical basis of the pathogenesis of sinus node dysfunction (SND) and atrial fibrillation (AF) is located primarily in the left and right atria, increasing evidence suggests a strong correlation between SND and AF, in terms of both clinical presentation and formation mechanisms. However, the exact mechanisms underlying this association are unclear. The relationship between SND and AF may not be causal, but is likely to involve common factors and mechanisms, including ion channel remodeling, gap junction abnormalities, structural remodeling, genetic mutations, neuromodulation abnormalities, the effects of adenosine on cardiomyocytes, oxidative stress, and viral infections. Ion channel remodeling manifests primarily as alterations in the "funny" current (If) and Ca2+ clock associated with cardiomyocyte autoregulation, and gap junction abnormalities are manifested primarily as decreased expression of connexins (Cxs) mediating electrical impulse propagation in cardiomyocytes. Structural remodeling refers primarily to fibrosis and cardiac amyloidosis (CA). Some genetic mutations can also cause arrhythmias, such as SCN5A, HCN4, EMD, and PITX2. The intrinsic cardiac autonomic nervous system (ICANS), a regulator of the heart's physiological functions, triggers arrhythmias.In addition, we discuss arrhythmias caused by viral infections, notably Coronavirus Disease 2019 (COVID-19). Similarly to upstream treatments for atrial cardiomyopathy such as alleviating CA, ganglionated plexus (GP) ablation acts on the common mechanisms between SND and AF, thus achieving a dual therapeutic effect.

Predictors of permanent pacemaker insertion after mitral valve replacement: A systematic review.

As the established surgical mitral valve replacement (MVR) expands toward various contemporary techniques and access routes, the predictors and burden of procedure-related complications including the need for permanent pacemaker (PPM) implantation need to be identified. Digital databases were searched systematically to identify studies reporting the incidence of PPM implantation after MVR. Detailed study and patient-level baseline characteristics including the type of study, sample size, follow-up, number of post-MVR PPM implantations, age, gender, and baseline ECG abnormalities were abstracted. A total of 12 studies, recruiting 37,124 patients were included in the final analysis. Overall, 2820 (7.6%) patients required a PPM with the net rate ranging from 1.7% to 10.96%. Post-MVR atrioventricular (AV) block was the most commonly observed indication for PPM, followed by sinoatrial (SA) node dysfunction, and bradycardia. Age, male gender, pre-existing comorbid conditions, prior CABG, history of arrhythmias or using antiarrhythmic drugs, atrial fibrillation ablation, and double valve replacement were predictors of PPM implantation post-MVR. Age, male gender, comorbid conditions like diabetes and renal impairment, prior CABG, double valve replacement, and antiarrhythmic drugs served as positive predictors of PPM implantation in patients undergoing MVR.

Early and Late Outcomes of the Warden and Modified Warden Procedure.

BACKGROUND: Operative repair of partial anomalous pulmonary venous connection (PAPVC) remains challenging due to risks of sinus node dysfunction, baffle obstruction, and superior vena cava (SVC) obstruction. METHODS: Traditional or modified Warden procedures were performed in 75 of 318 consecutive patients (24%) with PAPVC repaired surgically at our institution during 1993 to 2021. Clinical characteristics, echocardiography data, operative details, and early and late outcomes were collected. Cumulative incidence of reintervention and Kaplan-Meier survival analysis are reported. RESULTS: Median age was 39 years (interquartile range, 21-57 years). Fifty-nine (79%) had normal sinus rhythm preoperatively. Seventeen (23%) had intact atrial septa. Traditional and modified Warden procedures were performed in 15 (20%) and 60 (80%), respectively. Frequent concomitant procedures included 15 (20%) tricuspid valve repairs and 12 (16%) atrial fibrillation procedures. There were no early deaths. Postoperative complications included atrial fibrillation in 17 (23%), sinus node dysfunction in 15 (20%), pneumothorax in 3 (4%), pleural effusion in 2 (3%), and pacemaker implantation in 1 (1%). At hospital discharge, sinus node dysfunction persisted in 8 (11%). Over a median follow-up of 6 years (interquartile range, 4-10 years), baffle obstruction developed in 1 patient and SVC obstruction developed in 7. None required reoperation and 6 were treated with SVC stents. At 1, 5, and 10 years, the cumulative incidence of reintervention was 5%, 7%, and 14%, and survival was 99%, 94%, and 94%, respectively. CONCLUSIONS: Traditional and modified Warden procedures can be performed with satisfactory early and late survival. Persistent sinus node dysfunction and need for permanent pacing are low. Late SVC obstruction is uncommon and can often be managed nonoperatively.

Sinus Node Dysfunction Co-occurring with Immune Checkpoint Inhibitor-associated Myocarditis.

Immune checkpoint inhibitor (ICI)-induced myocarditis is a potentially life-threatening adverse event. We herein report a rare case of sick sinus syndrome (SSS) co-occurring with ICI-associated myocarditis. A 71-year-old woman with lung cancer undergoing pembrolizumab monotherapy was admitted owing to a fever, worsening kidney function, and sinus bradycardia. She was diagnosed with multi-organ immune-related adverse events, including myocarditis. Pulse steroid therapy was initiated immediately under the support of a temporary pacemaker, which resulted in the resolution of SSS in a few days. Biopsy specimens of the endomyocardium showed active myocarditis. Thus, we should be aware that SSS can co-occur with ICI-induced myocarditis.

First in human surgical implantation of a leadless pacemaker on the epicardial portion of the right atrial appendage in a patient with a cardiac electronic devices mediated dermatitis.

A 33-year-old woman with Sick Sinus Node syndrome and persistent atrial fibrillation underwent a Maze IV procedure in order treat atrial fibrillation and concomitant atrial epicardial implantation of a leadless pacemaker to manage her sinus node insufficiency. Last option has been chosen due to rare pocket complication after previous classic dual-chamber pacemaker implantation.

[Sinus node dysfunction associated with cardiac sarcoidosis: A case report]. / Dysfonction sinusale au cours de la sarcoïdose cardiaque: à propos d'un cas.

INTRODUCTION: Sarcoidosis is a multisystemic granulomatous disease of unknown cause occurring in young adults. Cardiac sarcoidosis patients are at increased risk for atrioventricular blocks and ventricular arrhythmias. Sinus node dysfunction is scarcely reported. OBSERVATION: We report a case of cardiac sarcoidosis revealed by a sinus node dysfunction and focus on cardiac and thoracic imaging to guide diagnosis. CONCLUSION: Sinus node dysfunction may be the first manifestation of cardiac sarcoidosis. In unexplained sinus node dysfunction in young patients, advanced cardiac imaging is a key to cardiac sarcoidosis diagnostic. Early recognition of cardiac sarcoidosis enables to start immunosuppressive treatment and discuss implantable cardioverter defibrillator implantation.

Secondary Cardiac Lymphoma Presenting as Sick Sinus Syndrome and Atrial Fibrillation Which Required Leadless Pacemaker Implantation.

Cardiac involvement of malignant lymphoma is relatively common, although such a phenomenon has subclinical manifestations that are difficult to detect. We herein describe a patient with atrial fibrillation and sick sinus syndrome as the main symptoms. Computed tomography showed a mass in the right atrium extending into the superior vena cava (SVC). We implanted the patient with a leadless pacemaker. Transvenous biopsy revealed a diffuse large B-cell lymphoma. The patient was treated successfully with chemotherapy including rituximab. This case suggested that cardiac lymphoma may cause sick sinus syndrome, and leadless pacemaker implantation is a safe treatment option in patients with partial SVC obstruction.

Prevalence and One-year Outcome of Carotid Sinus Hypersensitivity in Unexplained Syncope: A Prospective Cohort Study from South India.

BACKGROUND: Carotid sinus syndrome accounts for one third of patients who presents with unexplained syncope. Prevalence of carotid sinus hypersensitivity (CSH) in Indians has not been studied till now. OBJECTIVES: To assess the prevalence and associations of CSH in symptomatic patients above 50 years and to study its prognostic significance pertaining to sudden cardiac death, syncope, recurrent pre syncope and falls on 1 year follow up. METHODS: Patients above 50 years who presented with unexplained syncope, recurrent syncope or falls were considered cases and those without these symptoms were considered as controls. All the patients underwent carotid sinus massage and their responses noted. All symptomatic patients were followed up and observed for events like sudden cardiac death, syncope, recurrent pre syncope and falls during 1 year follow up. Patients with recurrent syncope and predominant cardioinhibitory syncope were advised permanent pacemaker implantation. RESULTS: A total of 252 patients were screened, 130 patients constituted cases and 49 patients constituted controls. CSH was demonstrable in 32% (n = 42) of cases as compared to 8% (n = 4) in controls (p < 0.001). Cardioinhibitory response was the predominant response (88%, n = 38) followed by mixed response (12%, n = 4). CSH was associated with advancing age, male gender (93%, n = 39, p < 0.001) and history of smoking (63%, n = 27, p = 0.009). Composite outcomes of sudden cardiac death, syncope, recurrent pre syncope and falls were significantly higher in patients with symptomatic CSH than in those without it (45%, n = 16 vs. 6.8%, n = 6; p < 0.001). CONCLUSIONS: In conclusion, the prevalence of CSH in patients above 50 yrs with unexplained syncope was high in our population. Patients with CSH and baseline symptoms developed recurrent syncope during follow up. Carotid sinus massage should be a part of routine examination protocol for unexplained syncope.

Unifocal Right-Sided Ablation Treatment for Neurally Mediated Syncope and Functional Sinus Node Dysfunction Under Computed Tomographic Guidance.

Background Biatrial, extensive, and complex ablation strategies have been published for the treatment of neurally mediated syncope, sinus node dysfunction, and functional atrioventricular block. We have developed a less extensive and more specific approach compared with previously published cardioneuroablation strategies, called cardio-neuromodulation. It is based on tailored vagolysis of the sinoatrial node through partial ablation of the anterior right-ganglionated plexus, preferentially through a right-sided approach. Methods Patients with syncope were enrolled between December 2016 and December 2017. They were assigned to group A if they had a positive head-up tilt test and to group B if they presented with a pause ≥3 seconds. The area to target during cardio-neuromodulation was designed offline on a computed tomographic scan. Slow heart rates and pauses were compared during 24-hour rhythm registration at baseline, at 1-month follow-up, and 6-month follow-up. Syncope burden was assessed before the procedure and at 3- and 6-month follow-up. Results Twenty patients underwent cardio-neuromodulation through a right-sided approach (12 in group A, 8 in group B). The first application of radiofrequency energy led to a P-P interval shortening >120 ms in all 20 patients. After a mean±SD ablation time of 7±4 minutes and mean ablated surface area of 11±6 mm2, the P-P interval shortened by 219±160 ms ( P<0.001). The number of beats <50/min during 24-hour rhythm registration was reduced by a median of 100% at 6-month follow-up ( P<0.001). Syncope burden was reduced by 95% at 6-month follow-up ( P<0.001). Conclusions These data indicate that cardio-neuromodulation, through a right-sided and computed tomographic-guided procedure, is safe, fast, and highly reproducible in preventing inappropriate functional sinus bradycardia and syncope recurrence.

Bradyarrhythmias in Repaired Atrioventricular Septal Defects: Single-Center Experience Based on 34 Years of Follow-Up of 522 Patients.

Atrioventricular Septal Defect (AVSD) is a rare congenital heart defect (CHD) often associated with genetic syndromes, most commonly Down syndrome (DS). Over the last four decades, surgical repair has increased survival and improved quality of life in these patients. The prevalence of bradyarrhythmias namely, atrioventricular block (AVB) and sinus node dysfunction (SND) in AVSD is partially known. 522 cases with both partial and complete AVSD (38.7% with DS), undergoing intracardiac repair from 1982 to 2016 at our institution, were reviewed from our system database. 38 (7.3%) patients received permanent PM implantation for AVB (early or late) or SND. On one hand, AVB requiring PM was found in 26 (4.98%). This was further subdivided into early-onset 14 (2.6%) and late-onset AVB 12 (2.2%) (median 4 [IQR 1-7] years). On the other hand, 12 (2.3%) experienced late SND requiring PM (median 11 [IQR 3.5-15.2] years). Early and late AVB were independent from the type of AVSD (partial or complete), whereas the late SND was remarkably observed in complete AVSD compared to partial AVSD (p = 0.017). We classified the cohort into two main categories: DS (202, 38.7%) and non-DS (320, 61.3%). At Kaplan-Meier survival analysis, DS was significantly associated with late-onset bradyarrhythmias (p = 0.024). At Cox regression analysis, we identified DS as an independent predictor of PM implantation (HR 2.17). In conclusion, about 7% of repaired AVSD patients need PM implantation during follow-up. There are no differences in early and late AVB occurrence according to the type of AVSD. There is a higher incidence of late SND in repaired complete AVSD, with a later timing onset in patients with associated DS. Moreover, DS seems to be an independent predictor of PM implantation.

Clinically oriented device programming in bradycardia patients: part 2 (atrioventricular blocks and neurally mediated syncope). Proposals from AIAC (Italian Association of Arrhythmology and Cardiac Pacing).

: The purpose of this two-part consensus document is to provide specific suggestions (based on an extensive literature review) on appropriate pacemaker setting in relation to patients' clinical features. In part 2, criteria for pacemaker choice and programming in atrioventricular blocks and neurally mediate syncope are proposed. The atrioventricular blocks can be paroxysmal or persistent, isolated or associated with sinus node disease. Neurally mediated syncope can be related to carotid sinus syndrome or cardioinhibitory vasovagal syncope. In sinus rhythm, with persistent atrioventricular block, we considered appropriate the activation of mode-switch algorithms, and algorithms for auto-adaptive management of the ventricular pacing output. If the atrioventricular block is paroxysmal, in addition to algorithms mentioned above, algorithms to maximize intrinsic atrioventricular conduction should be activated. When sinus node disease is associated with atrioventricular block, the activation of rate-responsive function in patients with chronotropic incompetence is appropriate. In permanent atrial fibrillation with atrioventricular block, algorithms for auto-adaptive management of the ventricular pacing output should be activated. If the atrioventricular block is persistent, the activation of rate-responsive function is appropriate. In carotid sinus syndrome, adequate rate hysteresis should be programmed. In vasovagal syncope, specialized sensing and pacing algorithms designed for reflex syncope prevention should be activated.

[A case of cardiogenic embolism, which occurred under appropriate warfarin use, treated with thoracoscopic left atrial appendectomy].

A 74-year-old man with a past medical history of bradycardiac atrial fibrillation and an old cerebral infarction presented with dysarthria. He had been treated with warfarin and PT-INR on admission was 2.0. MRI of the head revealed an acute ischemic stroke involving the cerebellum and left occipital lobe. Because transesophageal cardiac echography showed a thrombus in the left atrial appendage, anticoagulant treatment with warfarin and heparin was initiated. The thrombus was enlarging; therefore, we changed the anticoagulant therapy to apixaban with heparin on day 11. On day 17, a hemorrhagic cerebral infarction occurred. After the hemorrhage diminished, we treated him with warfarin aiming for a PT-INR between 3 and 4. The thrombus gradually shrank and disappeared on day 110. Finally, a thoracoscopic left atrial appendectomy was performed as a secondary prevention, with no recurrence till date.

Retrosternal Implantation of the Cardioverter-Defibrillator Lead in an Infant.

Using an implantable cardioverter-defibrillator (ICD) in small children is still challenging, but the need is increasing. We present a new approach to overcoming ICD problems caused by growth in infants. A redundant ICD lead was fixed to the superior border of the sternum and tunneled retrosternally to the subxiphoid region for connection to the generator, which was placed in a pocket beneath the left transversus abdominis muscle. The redundant retrosternal part of the lead straightened during growth, while cardiac coverage by the cardioversion energy field and the defibrillation vector were maintained appropriately.

An uncommon cause of syncope.

The authors present a case of a man with recurrent syncopal episodes. The patient had been hospitalized twice before reaching a correct diagnosis. The syncope was originally ascribed to a sick sinus syndrome, which led to pacemaker implantation. Nonetheless, the patient relapsed with no evidence of pacemaker dysfunction, and was readmitted to the hospital where the likely cause for his symptoms was identified: an adenocarcinoma of the lung infiltrating the vagus and recurrent laryngeal nerves. No further syncopal episodes occurred after thoracic surgery. This syncope led to an early diagnosis of lung cancer leading to appropriate and life extending treatment.

Correlating hemodynamic magnetic resonance imaging with high-field intracranial vessel wall imaging in stroke.

Vessel wall magnetic resonance imaging at ultra-high field (7 Tesla) can be used to visualize vascular lesions noninvasively and holds potential for improving stroke-risk assessment in patients with ischemic cerebrovascular disease. We present the first multi-modal comparison of such high-field vessel wall imaging with more conventional (i) 3 Tesla hemodynamic magnetic resonance imaging and (ii) digital subtraction angiography in a 69-year-old male with a left temporal ischemic infarct.

[Intraoperative asystole in a patient with concealed sick sinus syndrome: a case report].

We report a patient with concealed sick sinus syndrome who developed intraoperative bradycardia and asystole. An 81-year-old man was scheduled to undergo total gastrectomy under general and epidural anesthesia. There was no history of syncope, and preoperative 12-lead ECG showed normal sinus rhythm. Anesthesia was induced with propofol and remifentanil, maintained with sevoflurane, remifentanil and thoracic epidural infusion of lidocaine, fentanyl and levobupivacaine. Bradycardia was detected on ECG 110 minutes after the start of surgery. Intravenous atropine (0.5 mg, repeated up to a total dose of 1.5 mg) was ineffective in restoring a normal heart rhythm. Ten minutes later, the ECG changed to asystole lasting for about 15 seconds. Regular chest compression and intravenous administration of dopamine (5 microg x kg(-1) x min(-1)) resulted in successful recovery of sinus rhythm. Postoperative ECG showed sinus rhythm. The final diagnosis by a cardiologist was concealed sick sinus syndrome. Many anesthetic agents have some effects on the cardiac conduction system. Remifentanil may have played a role in the development of asystole in this patient. The existence of concealed sick sinus syndrome should be kept in mind even in patients who show no clinical abnormalities on preoperative assessment.

Syncope with atypical trunk convulsions in a patient with malignant arrhythmia.

Syncope is a condition often misdiagnosed as epilepsy. Syncope caused by cardiac disturbance is a life-threatening condition and accurate diagnosis is crucial for patient outcome. We present a case study of a 71-year-old woman who was referred to our epilepsy centre with a diagnosis of refractory epilepsy. We diagnosed convulsive syncope caused by malignant cardiac arrhythmia based on the presence of cardiac asystole lasting for 20-30 seconds, which was caused by sick sinus syndrome combined with third-degree atrioventricular block. The most prominent feature of this syncope was atypical trunk (abdominal or thoracoabdominal) convulsions, which were accompanied by other motor signs (head and eye deviation and brief jerks of the extremities). In the periods between attacks, all investigations, including standard 12-lead ECG and 24-hour ECG monitoring, were normal. This case study highlights the challenge in differential diagnosis of sudden loss of consciousness. [Published with video sequences].

Efeitos adversos em longo prazo da sobre-estimulação atrial dinâmica em pacientes com marcapasso e doença do nó sinusal / Long-term adverse effects of dynamic atrial overstimulation in patients with pacemaker and sinus node disease

Diversos estudos têm sido realizados a fim de mostrar a eficácia dos algoritmos na redução dos episódios da fibrilação atrial (FA). Dentre eles, destaca-se o ADOPT A (Atrial Dynamic Overdrive Pacing Trial - A), com o objetivo de avaliar a eficácia de um algoritmo de overpace atrial dinâmico (DAO - dynamic atrial overdrive) na redução de episódios de fibrilação atrial. Objetivo primário: Analisar os efeitos adversos do uso em longo prazo da sobre-estimulação atrial dinâmica em portadores de marcapasso para doença do nó sinusal do tipo síndrome braditaquicardia. Objetivo secundário: Avaliar a prevalência de possíveis efeitos adversos com o algoritmo e as consequências da FA, como: acidente vascular encefálico, embolia pulmonar, alterações cardíacas e outras causas. Método: Estudo observacional, retrospectivo, descritivo, no qual foi realizada a análise dos dados dos pacientes que implantaram marcapasso com software de sobre-estimulação atrial. Critério de inclusão: portador de MP com software overdrive programado em DDD cuja indicação baseou-se na presença de doença do nó sinusal do tipo síndrome braditaquicardia, em acompanhamento por um período mínimo de 48 meses. A coleta de dados foi feita por meio de consulta ao prontuário do paciente. Resultados: No que tange aos dados telemétricos encontrados, os diagnósticos dos 20 pacientes da amostra refletiram em uma média de 79,09 ± 5,39 episódios de troca (AMS), com janela em ciclos estimulados (OPC) de 28,54 ± 9,91, respeitando uma taxa básica de estímulos já programada de acordo com a mudança de modo. A frequência básica (BR) atingiu 62,9 ± 5,16 bpm em média.

Several studies have been conducted to demonstrate the effectiveness of algorithms in reducing atrial fibrillation episodes (AF). Among them, we highlight ADOPT A (Atrial Dynamic Overdrive Pacing Trial - A), with the aim of evaluating the dynamic algorithm overpace effectiveness (DAO - dynamic atrial overdrive) in reducing atrial fibrillation episodes. Primary Objective: Analyze database looking for long-term adverse effects of DAO in patients with pacemaker for sinus disease in type bradycardia-tachycardia syndrome. Secondary Objective: Evaluate the prevalence of possible adversities with the algorithm and consequences of FA as stroke, pulmonary embolism, cardiac abnormalities and other causes. Method: The project is an observational, retrospective, descriptive trial and analyzed data of patients whose pacemaker was implanted using an atrial overstimulation software. This protocol was approved by the ethics committee of the Catholic University of Goiás on March 04, 2013, with protocol number 210 302. Inclusion criteria: patients using a pacemaker implanted by an overdrive software programmed in DDD within a minimum of four (4) years, whose indication was based on the presence of sinus node disease type bradycardia-tachycardia syndrome. Data collection was obtained by assessing the patient’s chart...

[Long-term follow-up after implantable loop recorder in patients with syncope: results of a French general hospital survey]. / Suivi à long terme après pose de holter implantable pour syncope: résultats d'un registre mené dans un centre hospitalier.

BACKGROUND AND OBJECTIVE: Despite recent advances in diagnostic procedures, syncope remains unexplained in 15 to 35% of patients. If implantable loop recorder is a validated diagnostic tool for unexplained syncope, results of this strategy are largely issued from randomized studies. We lack the results of surveys. The aim of this study was to report a single center experience with implantable loop recorders, in patients with unexplained syncope. METHODS AND RESULTS: A device (Medtronic Reveal DX or XT) was implanted in 31 patients between January 2009 and January 2012. During a mean follow-up of 10.5±8.5 months, loop recording definitively determined that an arrhythmia was the cause of symptoms in 10 patients (32%). Fourteen patients (45%) experienced syncope or pre-syncope. In eight of the 14 patients with syncope, during follow-up, no arrhythmic diagnosis could be made (one patient has been diagnosed as presenting epilepsy and seven as having hypotensive vasovagal syncope). In six patients, the ILR showed an arrhythmic aetiology. Four other patients presented an abnormal ILR result without symptoms. Diagnosis included sinusal arrest in four patients, bradycardia in one patient, advanced atrioventricular block in two patients, ventricular arrythmias in two patients, and supraventricular tachycardia of 180/min in one patient. Therapy was instituted in all patients, in whom an arrhythmic cause was found except one who refused the therapy (six pacemaker, two implantable cardioverter-defibrillator implantations, and one cryoablation of atrioventricular nodal reentrant tachycardia confirmed by an invasive exploration). CONCLUSION: In this survey, implantable loop recorder implantation led to the diagnosis of an arrhythmic cause in 32% of patients and excluded an arrhythmic cause in 26% of patient with a mean follow-up of 10.5 months.