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.

Pacemaker implantation for persistent sinus node dysfunction in a patient with COVID-19.

A 46-year-old woman was admitted with coronavirus disease-2019 infection. Symptomatic sinus bradycardia occurred, followed by congestive heart failure. Therapeutics such as isoproterenol, theophylline, and cilostazol could not safely improve her symptoms. She underwent pacemaker implantation 53 days after admission. Atrial pacing remained was at 60% after 6 months.

Junctional bradycardia in a patient with COVID-19: A case report.

BACKGROUND: Cardiac arrhythmias, including bradyarrhythmias, have been described as manifestations of coronavirus disease 2019 (COVID-19). Herein, we present a case of junctional bradycardia secondary to possible sinus node dysfunction in a patient with COVID-19. CASE SUMMARY: The patient was a 32-year-old woman with no significant medical history. On the third day of hospitalization, she developed junctional bradycardia while being hemodynamically stable. The episodes of nodal dysrhythmia with a low heart rate persisted for the next few days and were associated with elevated levels of systemic inflammatory markers. The patient received antiviral and anti-inflammatory treatments for the viral infection but no antiarrhythmic medications. She had a normal sinus rhythm on day 12. CONCLUSION: Cardiac rhythm monitoring, focusing on the association between cardiac arrhythmias and the systemic inflammatory response, is important in COVID-19 patients.

Sinus Arrest in Asymptomatic COVID-19 Infection.

Coronavirus disease 2019 (COVID-19) is a viral respiratory tract syndrome capable of affecting a multitude of major organs in the human body. It is a known cause of severe vascular compromise, myocardial ischemia, myocarditis, and various cardiac dysrhythmias. Dysfunction of the sinoatrial (SA) node, the primary pacemaker of the heart, can arise from structural heart disease, medications, electrolyte abnormalities, and hypothyroidism. We report and discuss a case of a 50-year-old female with no significant past medical history (PMH) and no SA dysfunction risk factors, who experienced multiple syncopal events and an episode of sinus arrest characterized by transient asystole captured with telemetry monitoring. The patient was incidentally found to be COVID-19 positive and displayed no signs or symptoms concerning the viral illness. Despite our patient's lack of respiratory issues or other symptomatology, a significant and potentially fatal relationship exists between her viral infection and cardiac sequelae.

Bradyarrhythmias in patients with SARS-CoV-2 infection: A narrative review and a clinical report.

Several cardiovascular diseases and arrhythmic disorders have been described in COVID-19 era as likely related to SARS-CoV-2 infection. The prognostic relevance of bradyarrhythmias during the infection has not been yet described and no data are available about long-term heart conduction disorders. A review of literature concerning the association between hypokinetic arrhythmias and COVID-19 from January 2020 to February 2021 was performed. The key-words used for the research were: "sinus node disfunction," "sick sinus syndrome (SSS)," "sino-atrial block," "atrio-ventricular block (AVB)," "bradyarrhythmias," and "COVID-19″ or "SARS-CoV-2.″ Excluding "relative bradycardia," a total of 38 cases of bradyarrhythmia related to SARS-CoV-2 infection have been described, even in very young people, requiring in many cases a definitive pacemaker implantation. Furthermore, we report a case of non-hospitalized 47-years old man with a SSS developed as a consequence of mild SARS-CoV-2 infection. While in all described cases heart conduction disorders were found at presentation of the infection or during hospitalization for COVID-19, in our case the diagnosis of SSS was made after the resolution of the infection. Although rarely, heart conduction disorders may occur during COVID-19 and the present case highlights that a cardiological follow up may be desirable even after the resolution of infection, especially in the presence of symptoms suggesting a possible heart involvement.

Further insights into the molecular complexity of the human sinus node - The role of 'novel' transcription factors and microRNAs.

RESEARCH PURPOSE: The sinus node (SN) is the heart's primary pacemaker. Key ion channels (mainly the funny channel, HCN4) and Ca2+-handling proteins in the SN are responsible for its function. Transcription factors (TFs) regulate gene expression through inhibition or activation and microRNAs (miRs) do this through inhibition. There is high expression of macrophages and mast cells within the SN connective tissue. 'Novel'/unexplored TFs and miRs in the regulation of ion channels and immune cells in the SN are not well understood. Using RNAseq and bioinformatics, the expression profile and predicted interaction of key TFs and cell markers with key miRs in the adult human SN vs. right atrial tissue (RA) were determined. PRINCIPAL RESULTS: 68 and 60 TFs significantly more or less expressed in the SN vs. RA respectively. Among those more expressed were ISL1 and TBX3 (involved in embryonic development of the SN) and 'novel' RUNX1-2, CEBPA, GLI1-2 and SOX2. These TFs were predicted to regulate HCN4 expression in the SN. Markers for different cells: fibroblasts (COL1A1), fat (FABP4), macrophages (CSF1R and CD209), natural killer (GZMA) and mast (TPSAB1) were significantly more expressed in the SN vs. RA. Interestingly, RUNX1-3, CEBPA and GLI1 also regulate expression of these cells. MiR-486-3p inhibits HCN4 and markers involved in immune response. MAJOR CONCLUSIONS: In conclusion, RUNX1-2, CSF1R, TPSAB1, COL1A1 and HCN4 are highly expressed in the SN but not miR-486-3p. Their complex interactions can be used to treat SN dysfunction such as bradycardia. Interestingly, another research group recently reported miR-486-3p is upregulated in blood samples from severe COVID-19 patients who suffer from bradycardia.

Syncope Associated with Sinus Nodal Dysfunction in a COVID-19 Patient: A Case Report and Review of the Literature.

COVID-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is associated with significant cardiovascular dysfunction in patients with, and without, pre-existing cardiovascular disease [1]. There are now well-documented cardiac complications of COVID-19 infection which include myocarditis, heart failure, and acute coronary syndrome [2]. There is growing evidence showing that arrhythmias are also one of the major complications of COVID-19. We report a patient with no known cardiac conduction disease who presented with syncope, positive SARS-CoV-2 PCR, who was persistently bradycardic and subsequently developed sinus node dysfunction (SND). To date, there are a limited number of reports of sinus node dysfunction (SND) associated with COVID-19. We describe the clinical characteristics, potential pathophysiologic mechanisms and management of COVID-19 patients who experienced de novo SND.

Atrioventricular and Sinus Node Dysfunction in Stable COVID-19 Patients.

There are now well-documented cardiac complications of COVID-19 infection which include myocarditis, heart failure, and acute coronary syndrome resulting from coronary artery thrombosis or SARS-CoV-2-related plaque ruptures. There is growing evidence showing that arrhythmias are also one of the major complications. We report two patients with no known history of cardiac conduction disease who presented with COVID-19 symptoms, positive SARS-CoV-2 infection, and developed cardiac conduction abnormalities. Cardiac conduction system disease involving the sino-atrial (SA) node and atrioventricular (AV) node could be a manifestation of SARS-CoV-2 infection.

Sinus Node Dysfunction in a Young Patient With COVID-19.

A 34-year-old man was admitted with acute lung injury and COVID-19 pneumonia. In the intensive care unit, he experienced episodes of prolonged asystole accompanied by hypotension without loss of consciousness. Once reversible causes were excluded, symptoms were related to dysfunction of the sinus node, and the patient underwent implantation of a pacemaker. (Level of Difficulty: Beginner.).

Novel coronavirus 19 (COVID-19) associated sinus node dysfunction: a case series.

BACKGROUND: Novel coronavirus-19 disease (COVID-19) is associated with significant cardiovascular morbidity and mortality. To date, there have not been reports of sinus node dysfunction (SND) associated with COVID-19. This case series describes clinical characteristics, potential mechanisms, and short-term outcomes of COVID-19 patients who experience de novo SND. CASE SUMMARY: We present two cases of new-onset SND in patients recently diagnosed with COVID-19. Patient 1 is a 70-year-old female with no major past medical history who was intubated for acute hypoxic respiratory failure secondary to COVID-19 pneumonia and developed new-onset sinus bradycardia without a compensatory increase in heart rate in response to relative hypotension. Patient 2 is an 81-year-old male with a past medical history of an ascending aortic aneurysm, hypertension, and obstructive sleep apnoea who required intubation for COVID-19-induced acute hypoxic respiratory failure and exhibited new-onset sinus bradycardia followed by numerous episodes of haemodynamically significant accelerated idioventricular rhythm. Two weeks following the onset of SND, both patients remain in sinus bradycardia. DISCUSSION: COVID-19-associated SND has not previously been described. The potential mechanisms for SND in patients with COVID-19 include myocardial inflammation or direct viral infiltration. Patients diagnosed with COVID-19 should be monitored closely for the development of bradyarrhythmia and haemodynamic instability.