Development Of Sick Sinus Syndrome Research Articles

Novel Insights into the Sinoatrial Node in Single-Cell RNA Sequencing: From Developmental Biology to Physiological Function.

Normal cardiac automaticity is dependent on the pacemaker cells of the sinoatrial node (SAN). Insufficient cardiac pacemaking leads to the development of sick sinus syndrome (SSS). Since currently available pharmaceutical drugs and implantable pacemakers are only partially effective in managing SSS, there is a critical need for developing targeted mechanism-based therapies to treat SSS. SAN-like pacemaker cells (SANLPCs) are difficult to regenerate in vivo or in vitro because the genes and signaling pathways that regulate SAN development and function have not been fully elucidated. The development of more effective treatments for SSS, including biological pacemakers, requires further understanding of these genes and signaling pathways. Compared with genetic models and bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq) technology promises to advance our understanding of cellular phenotype heterogeneity and molecular regulation during SAN development. This review outlines the key transcriptional networks that control the structure, development, and function of the SAN, with particular attention to SAN markers and signaling pathways detected via scRNA-seq. This review offers insights into the process and transcriptional network of SAN morphogenesis at a single-cell level and discusses current challenges and potential future directions for generating SANLPCs for biological pacemakers.

ВАРИАНТ ГЕНА TNNI3K, АССОЦИИРОВАННЫЙ С СЕМЕЙНЫМ ЗАБОЛЕВАНИЕМ ПРОВОДЯЩЕЙ СИСТЕМЫ СЕРДЦА И СУПРАВЕНТРИКУЛЯРНОЙ ТАХИКАРДИЕЙ: КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ

Studying the genetic nature of cardiac arrhythmias and conduction disorders is extremely important. The genes (SCN5A, TRPM4, TNNI3K, LMNA, NKX2.5) associated with the development of sick sinus syndrome and diseases of heart conduction system are described. TNNI3K is a cardiospecific gene that encodes a MAP kinase that interacts with cardiac Troponin I. The enzyme TNNI3K kinase modulates cardiac conduction and myocardial function and plays an important role in the regulation of heart rate and cardiac contractility. A description of a family with an identified variant in the TNNI3K gene (c.1577G>A) and damage to the heart conduction system and supraventricular tachycardia is presented. The features of the familial clinical case represented by the authors are various phenotypic manifestations of the disease in different family members, the congenital nature of arrhythmia in some family members as well as the concentration of cases of sudden cardiac death in the family. It was the genetic diagnosis of the disease that determined the need to assess the condition of the heart cavities and its contractility in order to be able to timely correct the initial signs of dilated cardiomyopathy in the described family members.

A low dose of amiodarone-indused sinoatrial node dysfunction: a case report

We recently treated a case similar to that reported by Mun et al and Chinushi M. Holter ECG demonstrated paroxysmal atrial fibrillation, frequent ventricular ectopy’s, atrial tachycardia. The patient complained of palpitation. We have prescribed and amiodarone (100 mg/day) per day for 2 months. In the second visit, the palpitation attacks were relieved. It was effective in decreasing palpitation and atrial fibrillation. However, the patient was readmitted because of a new complaint of feeling weak, dizziness, confusion, and fainting. Holter monitoring revealed a long sinus pause (4–7,9 seconds). Because such a sinus pause had not been observed before the amiodarone treatment, it is likely that the development of sick sinus syndrome was related to amiodarone. Therefore, it seems inappropriate to apply this incidence of amiodarone-related sinoatrial node dysfunction to patients who are prescribed amiodarone for the treatment of ventricular tachyarrhythmia and atrial fibrillation who have prescribed a lower maintenance dose of amiodarone.

Comparative characteristics of a pacemaker implantation after biatrial or left atrial ablation of atrial fibrillation in combination with coronary artery bypass grafting in patients with ischemic heart disease and long-standing persistent atrial fibrillation.

Aim To compare the incidence of a permanent pacemaker (PP) implantation based on the chosen treatment technology (biatrial ablation, BA, or left atrial ablation (LAA) for long-standing persistent atrial fibrillation (AF) with simultaneous coronary bypass (CB).Material and methods The study included 116 patients with long-standing persistent AF and indications for CB. Patients were randomized to two equal groups (58 patients in each). Group 1 underwent BA in combination with CB; group 2 patients underwent isolated LAA with simultaneous CB under the conditions of artificial circulation. Incidence of PP implantation was assessed during the early (to 30 days) and late (to 60 months) postoperative periods.Results For the observation period, a total of 9 PPs was implanted in both groups, 6 in the BA group and 3 in the LAA group (odds ratio, OR, 0.5; 95 % confidence interval, CI, 0.1-2.4; р=0.490). During the early postoperative period, 5 patients in the BA group and 2 patients in the LAA group were implanted with PP (OR, 0.4; 95 % CI. 0-2.5; р=0.438). During the late postoperative period, one (2%) patient of the BA group was implanted with a permanent PP at 30 months of follow-up due to the development of sick sinus syndrome (SSS); also, one (2%) patient of the LAA group required PP implantation at 54 months of follow-up due to the development of SSS. The causes for PP implantation in the BA group included the development of complete atrioventricular (AV) block in 9 % of cases (95 % CI, 4-19 %); sinus node dysfunction and junctional rhythm in 2 % of cases (95 % CI, 0-9 %). Compared to this group, the LAA group showed a statistically significant difference in the incidence of AV block (0 cases, р=0.047). The major cause for PP implantation in the LAA group was the development of sinus node dysfunction in 3 (5 %) patients (95 % CI, 2-14 %).Conclusion The use of BA in surgical treatment of long-standing persistent AF with simultaneous myocardial revascularization is associated with a high risk of AV block, which requires permanent PP implantation in the postoperative period. Total incidence of permanent PP implantation for dysfunction of the cardiac conduction system following the combination surgical treatment of long-standing persistent AF and IHD, either CB and LAA or BA, did not differ between the treatment groups both in early and late postoperative periods.

Sick Sinus Syndrome After the Maze Procedure Performed Concomitantly With Mitral Valve Surgery.

BackgroundTo characterize the development of sick sinus syndrome (SSS) after the additive maze procedure (MP) during mitral valve surgery.Methods and ResultsFollow‐up data (median, 3.6 years) of 750 patients with a prevalence of rheumatic cause of 57.6% were analyzed. SSS occurred in 35 patients with a time‐dependent increase: the incidence rates at 1, 2, and 4 years after surgery were 2.9%, 3.7%, and 4.3%, respectively. The additive MP showed higher risks of SSS development (hazard ratio, 7.44; 95% confidence interval, 3.45–16.05; P<0.001) and pacemaker implantation (hazard ratio, 3.61; 95% confidence interval, 1.95–6.67; P<0.001). Patients who developed SSS showed higher 4‐year rates of clinical events (death, stroke, and hospital admission) (67.5±8.5% versus 33.0±1.9%; P<0.001). After adjustment for age and preoperative peak systolic pulmonary artery pressure, the lesion extent (biatrial versus left atrial MP), not the underlying cause (rheumatic versus nonrheumatic), was independently associated with SSS development (hazard ratio, 3.58; 95% confidence interval, 1.08–11.86; P=0.037). The adverse effect of the biatrial MP was confirmed in patients with trivial or mild preoperative tricuspid regurgitation showing higher SSS incidence (4.6±1.4% versus 1.0±0.7%; P=0.023), not in those with moderate‐to‐severe tricuspid regurgitation (6.8±1.7% versus 3.8±3.8%; P=0.337). Recurrence of atrial fibrillation was not associated with the lesion extent of the MP.ConclusionsAfter the additive MP, the ongoing risk of SSS development should be acknowledged irrespective of the underlying cause. Considering additive risk of biatrial MP with similar atrial fibrillation recurrence rate, minimizing lesion extent is warranted.

Sex-Dependent Phenotypic Variability of an SCN5A Mutation: Brugada Syndrome and Sick Sinus Syndrome.

BackgroundBrugada syndrome (BS) is known to be 9 times more prevalent in males than females. However, little is known about the development of sick sinus syndrome in female members with familial BS.Methods and ResultsFamilial BS patients and family members, both from our institutions and collaborating sites that specialize in clinical care of BS, participated in this study. We collected information on their clinical and genetic background, along with the inheritance patterns of BS. Detailed information on each case with familial BS is described. A total of 7 families, including 25 BS patients (12 females and 13 males), were included. Seven were probands and 18 were family members. Ten out of the 12 female patients and none of the 13 male patients developed sick sinus syndrome. Sudden death or spontaneous ventricular fibrillation occurred in 7 out of 13 male patients and 2 out of 12 female patients.ConclusionsFamilial BS existed in which female patients developed sick sinus syndrome but male patients did not. Some of those female patients with sick sinus syndrome had unrecognized BS. Information should be collected not only regarding a family history of sudden death or BS, but also whether a pacemaker was implanted in female members.

Sick sinus syndrome associated with anti-programmed cell death-1

BackgroundUse of anti-programmed cell death-1 (anti-PD-1) has been successful in treating many types of cancers. Despite its promising efficacy, immune-related adverse events are still a major concern. Immune-related cardiotoxicity, which is rare but fatal, has recently become a focus of attention. Cardiotoxicities including myocarditis, cardiomyopathy, cardiac fibrosis, heart block and cardiac arrest have been reported. Of these toxicities, myocarditis is often accompanied by dysrhythmia. The presentation of sick sinus syndrome as an immune-related adverse event has not yet been reported. Here, we reported the first case of sick sinus syndrome, a rare toxicity induced by anti-PD-1.Case presentationA 42-year-old male patient who had metastatic hepatocellular carcinoma failed treatment with sorafenib. Pembrolizumab at a fixed dose of 100 mg every three weeks was given. His heart rate gradually slowed down and he presented sick sinus syndrome with a lowest heart rate of 38 bpm after six cycles of pembrolizumab. He denied chest tightness, cold sweating, palpitation and dyspnea. Lab data including cardiac enzyme, electrolytes and thyroid function were all within a normal range. Simultaneously, he complained of fatigue, dizziness and anorexia with hypotension. Lab data revealed low cortisol and ACTH levels. Anti-PD-1 induced adrenal insufficiency was suspected. Low-dose cortisone (12.5 mg) was prescribed, and the patient’s symptoms, hypotension and sick sinus syndrome showed rapid improvement. Cortisone was gradually titrated and discontinued three weeks later. His sick sinus syndrome did not relapse and the cortisol and ACTH level returned to normal.ConclusionsSick sinus syndrome caused by anti-PD-1 treatment is a rare adverse event. With the development of sick sinus syndrome, myocarditis should be the first differential diagnosis because of its lethality. From this case, we learned that sick sinus syndrome may be a presentation of immune- or adrenal insufficiency-mediated sinus node dysfunction, both could be reversed with a glucocorticoid supplement.

Anaplastic lymphoma kinase-positive lung adenocarcinoma patient with development of sick sinus syndrome while on targeted treatment with crizotinib.

The anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients are younger and have never smoked, while pathologically are predominately adenocarcinomas. Crizotinib as an ALK inhibitor has been used in treating ALK positive NSCLC patients for several years and some adverse effects should be paid attention to. We now describe a case of ALK positive NSCLC patient with development of sick sinus syndrome (SSS) while on targeted treatment with crizotinib. A 46-year-old non-smoking woman with right hilar mass and underwent transesophageal endoscopic ultrasonography lymph node biopsy showed low differentiation adenocarcinoma, immunohistochemistry (IHC) of tumor samples revealed the ALK overexpression. The severe sinus bradycardia and RR interval prolongation were detected 3 months after crizotinib treatment, she underwent pacemaker implantation. Although the severe sinus bradycardia and RR interval prolongation were unusual adverse effects, physicians should be aware of these side effects when using crizotinib.

Modified Shumacker repair of transposition of the great arteries: Surgical and angiocardiographic considerations

Sixteen patients with transposition of the great arteries, 8 days to 2 1/2 years of age, underwent intra-atrial transposition of venous return by the modified Shumacker technique. A bipedicle flap of right atrial wall was used to direct vena caval return to the mitral valve, and a hinged viable flap of pericardium was used to form the lateral wall of the pulmonary venous pathway. Thirteen patients survived operation and are well to date. Two of the three nonsurvivors were less than 1 month of age at operation, and the third had an associated inlet ventricular septal defect and a straddling tricuspid valve. Early postoperative chest radiographs were compared with preoperative films in each patient. Postoperative findings included minor right pleural effusion in four, minor pneumothorax in two, and paralyzed right hemidiaphragm in one. Two patients required a permanent pacemaker because of the development of sick sinus syndrome 2 and 4 years postoperatively. Each preoperative angiocardiogram was reviewed and compared with postoperative studies in nine patients. The latter demonstrated absence of caval gradients in each, trivial baffle leaks in four, a moderate baffle leak in one, small residual ventricular septal defects in two, and mild tricuspid regurgitation in two patients.

Sick sinus syndrome after surgery for congenital heart disease.

The course and prognosis of 16 infants and children with sick sinus syndrome associated with cardiac surgery is reviewed. The dysrhythmia was observed most ofter after extensive atrial reconstructive surgery in patients with transposition of the great arteries and with atrial septal defect. In 12 (75%) of the patients, sick sinus syndrome was detected in the immediate postoperative period. Tachyarrhythmias and bradyarrhythmias were presnet in 12 and isolated bradyarrhythmias in four. Temporary pacing was used in two and permanent pacing was required in five. Death in two non-paced patients was attributable to arrhythmias. Postmortem examination in one patient revealed a suture in the sinoatrial node. Careful attention to the anatomy of the sinoatrial node, its artery and the internodal tracts during surgery may prevent the development of sick sinus syndrome. In patients with dysrhythmia, a careful search should be undertaken to document the abnormal rhythm with the use of Holter monitoring. The insertion of a pacemaker is indicated in patients with tachyarrhythmias requiring cardioversion or antiarrhythmic drug therapy and those without adequate lower escape mechanisms.