Comparison between catheter ablation versus permanent pacemaker implantation as an initial treatment for tachycardia-bradycardia syndrome patients: a prospective, randomized trial.

BACKGROUND: Clinical outcomes after catheter ablation (CA) or pacemaker (PM) implantation for the tachycardia-bradycardia syndrome (TBS) has not been evaluated adequately. We tried to compare the efficacy and safety outcomes of CA and PM implantation as an initial treatment option for TBS in paroxysmal atrial fibrillation (AF) patients. METHODS: Sixty-eight patients with paroxysmal AF and TBS (mean 63.7 years, 63.2% male) were randomized, and received CA (n = 35) or PM (n = 33) as initial treatments. The primary outcomes were unexpected emergency room visits or hospitalizations attributed to cardiovascular causes. RESULTS: In the intention-to-treatment analysis, the rates of primary outcomes were not significantly different between the two groups at the 2-year follow-up (19.8% vs. 25.9%; hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.25-2.20, P = 0.584), irrespective of whether the results were adjusted for age (HR 1.12, 95% CI 0.34-3.64, P = 0.852). The 2-year rate of recurrent AF was significantly lower in the CA group compared to the PM group (33.9% vs. 56.8%, P = 0.038). Four patients (11.4%) in the CA group finally received PMs after CA owing to recurrent syncope episodes. The rate of major or minor procedure related complications was not significantly different between the two groups. CONCLUSION: CA had a similar efficacy and safety profile with that of PM and a higher sinus rhythm maintenance rate. CA could be considered as a preferable initial treatment option over PM implantation in patients with paroxysmal AF and TBS. TRIAL REGISTRATION: KCT0000155.

The effectiveness and safety of temporary transvenous cardiac pacing leads placement into coronary sinus vein in patients with sick sinus syndrome.

BACKGROUND: The temporary pacing lead routinely is placed into right ventricular (RV), which pose a risk of dislocation and cardiac perforation. OBJECTIVE: We aim to evaluate the effectiveness and safety of temporary transvenous cardiac pacing (TTCP) leads placement into the coronary sinus vein (CSV) in patients with sick sinus syndrome (SSS). METHODS: We investigated patients with SSS who underwent TTCP lead placement into the CSV under the guidance of X-ray between January 2013 and May 2023. Patients were randomly divided into two groups: RV group (n = 33) and CSV group (n = 22). The ordinary passive bipolar electrodes were applied in both groups. In RV groups, electrodes were placed into RV. In CSV group, electrodes were placed into CSV. We evaluated the operation duration, fluoroscopic exposure, first-attempt success rate of leads placement, pacing threshold, success rate of leads placement, rate of leads displacement, and complications. RESULTS: Compared with that in RV group, the procedure time, fluoroscopic exposure was significantly prolonged, while the first-attempt success rate of lead placement was obviously increased in CSV group (both p < .05). Compared with that in RV group, the rate of leads displacement is lower in CSV group (both p < .05). There were three patients occurred cardiac perforation in RV group, but no cardiac perforation was reported in CSV group (p > .05). CONCLUSION: TTCP leads placement into the CSV is an effective and safe strategy in patients with SSS. It indicates a high rate of pacing effectiveness with low device replacement and complication rates.

Yixin-Fumai granules modulate autophagy through the PI3K/AKT/FOXO pathway and lead to amelioration of aging mice with sick sinus syndrome.

OBJECTIVE: By employing network pharmacology alongside molecular docking techniques, we can delve into the intricate workings of Yixin-Fumai granules (YXFMs) and their impact on sick sinus syndrome (SSS) within wrinkles mice. Specifically, we aim to understand how YXFMs enhance autophagy through the PI3K/AKT/FOXO path. METHODS: The active ingredients and medicinal uses of Ginseng, ligusticum wallichii, Ophiopogon, Schisandra, salvia, and astragalus were compiled using the BATMAN-TCM database. We also used Genecards, OMIM, and Disgenet files to identify the disease goals. A hierarchical diagram of "disease-drug-key targets" was generated using the Cytoscape programs. In addition, we established a target protein interaction (PPI) network using the STRING database. Then, the Cluster Profiler R package was used to conduct GO functional enrichment evaluation and KEGG pathway enrichment analyses of the targets. Based on the PPI system, we chose the top communicating targets and substances over molecular docking. In vivo studies were performed to validate these selections further. The mouse model was induced to study the damaged sinoatrial node (SAN) in mice with lower heart rates due to age-related changes. Electrocardiogram and Masson staining assessments were performed to obtain the results. The transmission electron microscope was used to assess the autophagy level of SAN cells. Western blot was employed to analyze the impact of YXFMs on protein expression in the PI3K/AKT/FOXO signaling process throughout SSS therapy in aging mice. RESULTS: One hundred forty-two active ingredients, 1858 targets, 1226 disease targets, and 266 intersection targets were obtained. The key targets of the PPI network encompassed TP53, AKT1, CTNNB1, INS, and TNF, among others. According to GO functional analysis, the mechanism underlying YXFMs in SSS treatment may primarily be associated with the control of ion transport across membranes, cardiac contraction, regulation of blood circulation, and other biological processes. Based on the results of KEGG pathway enrichment analysis, it was determined that they were mainly enriched in multiple pathways of signaling such as the PI3K-Akt signaling route, MAPK signaling process, AGE-RAGE signaling path, FOXO signaling path, HIF-1 signaling process, and several other paths. Molecular docking demonstrated that five compounds had excellent binding to the key candidate target proteins AKT1 and INS. Through the in vivo studies, we noticed notable effects when administering YXFMs. These effects included the suppression of aging-induced SSS, a decrease in the R-R interval, a rise in heart rate, a reduction in fibrosis, a boost in the autophagy process level, and a spike in the levels of expression of key protein molecules in the PI3K/AKT/FOXO signaling path. CONCLUSION: This research has made preliminary predictions about the potential of YXFMs in treating SSS. It suggests that YXFMs may have the ability to target key proteins and critical paths associated with the condition. Further testing has been conducted to discover new findings and evidence of ideas for tackling SSS triggered by aging.

Early Experience of Left Bundle Branch Pacing with Lumenless Lead in a Single Center: A Case Series.

Left bundle branch pacing (LBBP) has been subject to increasing interest over the last few years due to its capacity for physiological conduction and its advantages compared to His bundle pacing. His bundle pacing has certain limitations, such as a small pacing area for the His bundle, a high threshold that leads to battery depletion, a low R-wave amplitude that may result in atrial or His oversensing, and ventricular signal undersensing. In this case series, four patients (two female and two male) aged 62.2 ± 8.4 years old with symptomatic sick sinus disease and no scar tissue in the interventricular septum underwent LBBP. All LBBPs were done with standard LBBP using a lumenless SelectSecure 3830 lead (Medtronic®, Minneapolis, USA) with a fixed helix. The lead parameters showed a good R-wave amplitudes (13 ± 7.4 mV) and a low threshold  (0.77 ± 0.17 V @ 0.4 ms). All patients were discharged on the next day. During follow-up period of 13.3 ± 12.9 months, all patients were well and no complications were noted. In conclusion, LBBP may be as an alternative of novel conduction pacing techniques and can be done relatively easy and safe, even with limited experience center.

Leadless pacemaker implantation in dextrocardia with situs viscerum inversus: A case report and literature review.

Leadless pacemaker implantation (LPI) has fewer device complications and reduced chance of infection compared to conventional pacemakers. Dextrocardia with situs viscerum inversus (DC+SVI) is a rare condition, which seldom leads to cardiac complications. However, its presence poses a challenge to operators in cardiac procedures. LPI reports in DC patients are scarce. We report a case of LPI in a DC+SVI patient, followed by a brief but comprehensive literature review.

Hospitalization for permanent pacemaker implantation in the context of isolated sinus node dysfunction is associated with increased mortality compared with an outpatient strategy.

BACKGROUND: Permanent pacemaker (PPM) implantation is a well-established treatment for symptomatic sinus node dysfunction (SND). The optimal timing of this intervention is unclear, with atrioventricular blocks often prioritized in resource stressed waiting lists due to mortality concerns. METHODS: Mortality data was compared between patients receiving elective outpatient (OP) PPM implantation, and those presenting to hospital for urgent inpatient (IP) management for symptomatic SND. Survival analysis was conducted using Kaplan-Meier plots and compared using the log-rank test. Univariable and multivariable Cox regression, as well as propensity score matching analyses were performed to assess the prognostic effect on 30-day and 1-year all-cause mortality of inpatient implant. RESULTS: Of the 1269 patients identified with isolated SND, 740 (58%) had PPMs implanted on an OP and 529 (42%) on an IP basis. Mortality was significantly worse in patients where management was driven by hospital admission on an urgent basis (Log-Rank χ2 = 21.6, p < 0.001) and remained an independent predictor of 1-year all-cause mortality (HR 3.40, 95% CI 1.97-5.86, p < 0.001) on multivariable analysis. CONCLUSIONS: SND is predominantly a disease associated with ageing and comorbid populations, where avoidance of deconditioning, hospitalization acquired infections, and polypharmacy is advantageous. Admission avoidance is therefore the preferable strategy.

Exploring the prevalence of undetected bradyarrhythmia in dementia with Lewy bodies.

PURPOSE: To explore the prevalence of undetected bradyarrhythmia in a cohort of people with dementia with Lewy bodies. METHODS: Thirty participants diagnosed with dementia with Lewy bodies were enrolled from three memory clinics in southern Sweden between May 2021 and November 2022. None had a history of high-grade atrioventricular block or sick sinus syndrome. Each participant underwent orthostatic testing, cardiac [123I]metaiodobenzylguanidine scintigraphy and 24-h ambulatory electrocardiographic monitoring. Concluding bradyarrhythmia diagnosis was obtained until the end of December 2022. RESULTS: Thirteen participants (46.4%) had bradycardia at rest during orthostatic testing and four had an average heart rate < 60 beats per minute during ambulatory electrocardiographic monitoring. Three participants (10.7%) received a diagnosis of sick sinus syndrome, of whom two received pacemaker implants to manage associated symptoms. None received a diagnosis of second- or third-degree atrioventricular block. CONCLUSION: This report showed a high prevalence of sick sinus syndrome in a clinical cohort of people with dementia with Lewy bodies. Further research on the causes and consequences of sick sinus syndrome in dementia with Lewy bodies is thus warranted.

Recurrent syncope in patients with a pacemaker and bradyarrhythmia.

Background. Pacemakers are used to treat syncope in patients with bradyarrhythmia; however, the risk of recurrent syncope has only been investigated in few and smaller studies. Objective. The aim of this study was to investigate the risk of recurrent syncope after pacemaker implantation in patients with bradyarrhythmia and prior syncope. Methods. This retrospective, population-based cohort study included patients with a prior syncope and implantation of a pacemaker using data from the Danish nationwide registers from 1996 to 2017. Cumulative incidence and cox regression was used to estimate the 5-year incidence and the risk of recurrent syncope, respectively. Results. In total, 11,126 patients (median age: 78 years, interquartile range: 69-85, 56% male) were included and the 5-year cumulative incidence of recurrent syncope was 19.6% (95% confidence interval (CI): 18.8-20.3%). Sinus node dysfunction (hazard ratio [HR]: 1.29, 95%CI: 1.17-1.42) and unspecified type of bradyarrhythmia (HR: 1.32, 95%CI: 1.15-1.52) were associated with an increased risk of syncope compared to advanced atrioventricular (AV) block. Male sex (HR: 1.22, 95%CI: 1.22-1.34), cerebrovascular disease (HR: 1.17, 95%CI: 1.05-1.30), and prior number of syncopes were significantly associated with a higher HR of recurrent syncope. Conclusion. Almost one-in-five patients with bradyarrhythmia and prior syncope who had a pacemaker implanted had a recurrent syncope within five years. A higher risk of syncope was observed among patients with sinus node dysfunction and unspecified type of bradyarrhythmia compared to AV block. Male sex, cerebrovascular disease, and prior number of syncopes were associated risk factors of recurrent syncope.

Catheter Ablation for Paroxysmal Atrial Fibrillation With Sick Sinus Syndrome: Insights From the Kansai Plus Atrial Fibrillation Registry.

BACKGROUND: Coexisting sick sinus syndrome (SSS) is associated with both electrical and structural atrial remodelling in patients with atrial fibrillation (AF). Limited data are available concerning catheter ablation (CA) for AF in this condition. This study investigated the efficacy of CA as a curative therapy for AF and SSS in a large-scale prospective multicentre registry. METHODS: The Kansai Plus Atrial Fibrillation (KPAF) registry enrolled 5,010 consecutive patients who underwent CA for AF; this included 3,133 patients with paroxysmal AF (mean age, 66 years; male, 69.3%; mean CHA2DS2-VASc score, 2.05±1.50; SSS, n=315 [tachy-brady syndrome, n=285]). The endpoints included the recurrence of AF with a blanking period of 90 days after CA, and de novo pacemaker implantation during the follow-up period (median duration, 2.93 years). RESULTS: The AF-free survival did not significantly differ between patients with and those without SSS (n=2,818) after the initial (log-rank p=0.864) and final sessions (log-rank p=0.268). Pacemakers were implanted in 48 patients with SSS, and implantation in this group was significantly associated with AF recurrence, including early recurrence (adjusted odds ratio, 3.57; 95% confidence interval, 1.67-7.64; p=0.002). The remaining 85.3% of patients with SSS did not require pacemaker implantation at 3 years after CA. CONCLUSIONS: Coexisting SSS did not adversely affect recurrence-free survival after CA for paroxysmal AF. Pacemaker implantation was not required in most patients with SSS, with AF recurrence serving as a strong predictor for this.

Sick sinus syndrome diagnosed after a sinus arrest during treatment for zygomatic fracture: a case report.

BACKGROUND: Intraoperative sinus arrest is rarely seen during zygomatic fracture treatment. The patient was diagnosed with sick sinus syndrome based on repeated postoperative sinus arrest, which could have resulted in death if diagnosed late, making this case very significant to report. CASE PRESENTATION: Sick sinus syndrome is an arrhythmia associated with reduced automaticity of the sinoatrial node or impaired sinoatrial node conduction. We report the case of a 67-year-old man diagnosed with the syndrome after a sinus arrest that occurred during a zygomatic fracture treatment. The patient had cheek pain and mouth opening disorder, dizziness after fainting and sustaining a facial injury. Preoperative examination determined that the syncope was due to drug-induced arrhythmia, and surgery was authorized after drug withdrawal. During the operation, sinus arrest was observed due to trigeminal vagal reflex, and heart rate was restarted by stopping the operation and chest compressions. After the surgery, the patient showed symptoms of dizziness and palpitations, and sinus arrest following atrial fibrillation and supraventricular tachycardia, which was diagnosed as sick sinus syndrome, and a pacemaker was implanted. Currently, 8 years have passed since the surgery, and there are no symptoms of mouth opening disorder, dizziness, or palpitations. CONCLUSIONS: In the case of maxillofacial injuries due to syncope, cardiogenic syncope is a possibility, and repeated syncope is a risk for death due to delayed diagnosis. There are no reports of maxillofacial trauma leading to a diagnosis of sick sinus syndrome. The purpose of this case report is to disseminate the importance of diagnosing the cause of syncope as well as injury treatment.

[Regularity of prescriptions for sick sinus syndrome based on latent structure combined with association rules].

This study aims to mine the regularity of traditional Chinese medicine(TCM) prescriptions for sick sinus syndrome(SSS) and provide a reference for clinical syndrome differentiation and treatment. The relevant papers were retrieved from CNKI, Wanfang, VIP, and SinoMed with the time interval from inception to January 31, 2023. The relevant information from qualified papers was extracted to establish a library. Lantern 5.0 and Rstudio were used to analyze the latent structure and association rules of TCMs with the frequency ≥3%, which combined with frequency descriptions, were used to explore the rules of TCM prescriptions for SSS. A total of 192 TCM prescriptions were included, involving 115 TCMs with the cumulative frequency of 1 816. High-frequency TCMs include Aconiti Lateralis Radix Praeparata, Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, Astragali Radix, and Salviae Miltiorrhizae Radix et Rhizoma. The high-frequency medicines mainly had the effects of tonifying, releasing exterior with pungent-warm, and activating blood and resolving stasis. The analysis of the latent structure model yielded 13 hidden variables, 26 hidden classes, 8 comprehensive cluster models, and 21 core prescriptions. Accordingly, the common syndromes of SSS were inferred as heart-Yang Qi deficiency, heart-spleen Yang deficiency, heart-kidney Yang deficiency, Yang deficiency and blood stasis, both Qi and Yin deficiency and blood stasis, and Yin and Yang deficiency. The analysis of association rules predicted 30 strong association rules, among which Ginseng Radix et Rhizoma-Aconiti Lateralis Radix Praeparata had the highest support. SSS is a syndrome with Yang deficiency and Qi deficiency as the root causes and cold, phlegm, and stasis as the manifestations. The clinical treatment of SSS should focus on warming Yang and replenishing Qi, which should be supplemented with the therapies of activating blood and resolving stasis, warming interior and dissipating cold, or regulating Qi movement for resolving phlegm according to the patients' syndromes.

Whole genome sequencing identifies a deletion mutation in the unknown-functional KCNG2 from familial sick sinus syndrome.

Sick sinus syndrome (SSS) is a term used for a variety of disorders defined by abnormal cardiac impulse formation and by abnormal propagation from the heart's sinoatrial node. In this study, we present a case from a Chinese family in which two closely related individuals had the symptoms and electrocardiographic evidence of SSS. We hypothesized that multiple individuals affected by the disease in the family was an indication of its genetic predisposition, and thus performed high-throughput sequencing for the participants from the family to detect potential disease-associated variants. One of the potential variants that was identified was a KCNG2 gene variant (NC_000018.9: g.77624068_77624079del). Further bioinformatic analysis showed that the observed variant may be a pathogenic mutation. The results of protein-protein docking and whole cell patch-clamp measurements implied that the deletion variant in KCNG2 could affect its binding the KV2.1 protein, and finally affect the function of Kv channel, which is an important determinant in regulation of heartbeat. Therefore, we inferred that the variable KCNG2 gene may affect the function of Kv channel by changing the binding conformation of KCNG2 and KV2.1 proteins and then adversely affect propagation from the sinoatrial node and cardiac impulse formation by changing the action potential repolarization of heart cells. In summary, our findings suggested that the dominant KCNG2 deletion variant in the examined Chinese family with SSS may be a potential disease-associated variant.

A 15-year follow-up study of radiofrequency catheter ablation for atrial fibrillation in patients with tachycardia-bradycardia syndrome.

INTRODUCTION: Catheter ablation for atrial fibrillation (AF) in patients with tachycardia-bradycardia syndrome (TBS) can be a major therapeutic option to replace permanent pacemaker implantation (PMI). However, the very long-term outcome of more than 15 years in these patients has not been elucidated. METHODS: From 2002 to 2008, 25 consecutive TBS patients (62 ± 7.9 years old, 68% male) with both AF and symptomatic sinus pauses (>3.0 s) were performed radiofrequency AF ablation. These patients were followed for 15 ± 2.7 years. RESULTS: The median longest sinus pause before the ablation procedure was 6.0 s (4.4-8.0). Following 1.6± 0.8 ablation procedures, 18 (72%) patients remained free from AF. Three (12%) patients died due to noncardiovascular causes, and seven (28%) patients underwent PMI due to symptomatic sinus pause after recurrent AF in five patients and progression of sinus node dysfunction in two patients. The median duration from the first AF ablation to PMI was 6.3 years (range: 9 days to 11.0 years). Five and two patients required PMI more than 5 and 10 years after the first ablation procedure, respectively. CONCLUSION: AF ablation prevented PMI in 72% of TBS patients for a 15-year follow-up. However, in consideration of the long duration of PMI, a continuous careful long-term follow-up was warranted.

Impact on right ventricular performance in patients undergoing permanent pacemaker implantation: Left bundle branch pacing versus right ventricular septum pacing.

BACKGROUND: The novel method of left bundle branch pacing (LBBP) has been reported to achieve better electrical and mechanical synchrony in the left ventricle than conventional right ventricular pacing (RVP). However, its effects on right ventricle (RV) performance are still unknown. METHODS: Consecutive patients undergoing dual-chamber pacemaker (PM) implantation for sick sinus syndrome (SSS) with normal cardiac function and a narrow QRS complex were recruited for the study. The pacing characteristics and echocardiogram parameters were measured to evaluate RV function, interventricular and RV synchrony, and were compared between ventricular pacing-on and native-conduction modes. RESULTS: A total of 84 patients diagnosed with SSS and an indication for pacing therapy were enrolled. Forty-two patients (50%; mean age 65.50 ± 9.30 years; 35% male) underwent successful LBBP and 42 patients (50%; mean age 69.26 ± 10.08 years; 33% male) RVSP, respectively. Baseline characteristics were similar between the two groups. We found no significant differences in RV function [RV-FAC (Fractional Area Change)%, 47.13 ± 5.69 versus 48.60 ± 5.83, p = .069; Endo-GLS (Global Longitudinal Strain)%, -28.88 ± 4.94 versus -29.82 ± 5.35, p = .114; Myo-GLS%, -25.72 ± 4.75 versus -25.72 ± 5.21, p = .559; Free Wall St%, 27.40 ± 8.03 versus -28.71 ± 7.34, p = .304] between the native-conduction and LBBP capture modes, while the RVSP capture mode was associated with a significant reduction in the above parameters compared with the native-conduction mode (p < .0001). The interventricular synchrony in the LBBP group was also superior to the RVSP group significantly. CONCLUSION: LBBP is a pacing technique that seems to associate with a positive and protective impact on RV performance.

Sick sinus syndrome as the initial manifestation of neuromyelitis optica spectrum disorder: a case report.

BACKGROUND: Sick sinus syndrome (SSS) is known to occur due to lesions in the medulla oblongata. Although medullary lesions have occurred in patients with neuromyelitis optica spectrum disorder (NMOSD), there are few reports of SSS associated with NMOSD. We report a patient with NMOSD who developed refractory nausea, vomiting and SSS as the initial manifestation. CASE PRESENTATION: A 77-year-old female developed refractory nausea and frequent episodes of syncope. The patient was diagnosed with SSS because sinus pauses lasting five to six seconds were observed, and pacemaker implantation was performed. Two months later, she was referred to our hospital because of limb weakness and sensory impairment that progressed over a month. The patient was confirmed to have muscle weakness; manual muscle testing revealed grade 4 in the upper extremities and grade 3 in the lower extremities. Tendon reflexes were diminished, while no pathological reflexes were present. Thermal and pain sensations were impaired in the upper and lower extremities, and vibration sensation was impaired in both lower extremities. Bladder and rectal disturbances were also noted. Optic neuritis was not detected. T2-weighted magnetic resonance imaging (MRI) showed high-intensity lesions in the dorsal part of the medulla oblongata and C3-6 cervical cord. Her serum was positive for antibodies against aquaporin 4, and a diagnosis of NMOSD was made. She was treated with two courses of an intravenous methylprednisolone pulse and one course of plasma exchange. Then, she was transferred to another hospital for rehabilitation. CONCLUSIONS: Because SSS is a life-threatening complication, clinicians should be aware of the possibility that medullary lesions in NMOSD can cause SSS as the initial manifestation.

Characteristics of bradyarrhythmia in patients with COVID-19: Systematic scoping review.

COVID-19 has recently been associated with the development of bradyarrhythmias, although its mechanism is still unclear. We aim to summarize the existing evidence regarding bradyarrhythmia in COVID-19 and provide future directions for research. Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including"Bradycardia," "atrioventricular block," and "COVID-19″ from their inception to October 13, 2021. Forty-three articles, including 11 observational studies and 59 cases from case reports and series, were included in the systematic review. Although some observational studies reported increased mortality in those with bradyarrhythmia and COVID-19, the lack of comparative groups and small sample sizes hinder the ability to draw definitive conclusions. Among 59 COVID-19 patients with bradycardia from case reports and series, bradycardia most often occurred in those with severe or critical COVID-19, and complete heart block occurred in the majority of cases despite preserved LVEF (55.9%). Pacemaker insertion was required in 76.3% of the patients, most of which were permanent implants (45.8%). This systematic review summarizes the current evidence and characteristics of bradyarrhythmia in patients with COVID-19. Further studies are critical to assess the reversibility of bradyarrhythmia in COVID-19 patients and to clarify potential therapeutic targets including the need for permanent pacing.

Mitral valvuloplasty with left atrial appendage closure and pacemaker implantation in a dog with severe myxomatous mitral valve degeneration: a case report.

BACKGROUND: Mitral valvuloplasty (MVP) has been widely recognized as a treatment option for myxomatous mitral valve disease (MMVD). However, postoperative complications such as thromboembolism, arrhythmia, and pancreatitis in some cases have resulted in death. We treated a dog with severe MMVD complicated by impaired sinus function with MVP and pacemaker implantation. Also, due to an intrinsic procoagulant state and severe arrhythmia after the MVP, left atrial appendage (LAA) closure was performed to reduce the postoperative risk of thrombosis. CASE PRESENTATION: An 11-year-old castrated 7.5-kg male Miniature Schnauzer with a history of congestive heart failure was brought to Shiraishi Animal Hospital for MMVD surgical treatment. Echocardiography revealed an enlarged left atrium and ventricle secondary to MMVD. Sinus arrest with 2 to 3-second periods of asystole was identified by electrocardiogram. Mitral valvuloplasty was performed with cardiopulmonary bypass to treat the MMVD. After coronary reperfusion, there was no spontaneous electrical activity. Cardiac arrest continued. Based on this surgical outcome, a permanent pacemaker was implanted. In addition, LAA closure with an AtriClip was performed to prevent intra-atrial thrombus formation. Cardiac remodeling and congestion were ameliorated after surgery. Sinus rhythm was restored 5 days postoperatively; however, the patient continued pacemaker dependent. All cardiac drugs were discontinued 3 months after surgery. The owner reported no postoperative complications (i.e., thrombosis), and the patient was brought for a check-up 4 months after the operation in good health. CONCLUSIONS: For surgical MMVD cases complicated with impaired sinus function, the chances of spontaneous sinus rhythm are low, requiring pacemaker implantation. LAA closure may be considered to protect against decreased atrial function after mitral valvuloplasty and prevent intra-atrial thrombus formation.

Clinical review of sick sinus syndrome and atrial fibrillation.

Sick sinus syndrome (SSS) is a set of diseases with abnormal cardiac pacing, which manifests as diverse cardiac arrhythmias, especially bradycardia. The clinical presentation is inconspicuous in the early stage, but with the progression of this disease, patients may present with symptoms and signs of end-organ hypoperfusion. As a common result in the natural history of the disease, SSS coexisting with atrial fibrillation (AF) forms the basis of bradycardia-tachycardia syndrome. Age-related interstitial fibrosis is considered to be the common pathophysiological mechanism between SSS and AF. The combination of these diseases will adversely affect the condition of patients and the efficiency of subsequent treatment. Although the exact mechanism is not clear to date, the extensive structural and electrical remodeling of the atrium are considered to be the important mechanism for the occurrence of AF in patients with SSS. Pacemaker implantation is the first-line treatment for symptomatic patients with SSS and documented bradycardia history. In view of the adverse effects of AF on the treatment of SSS, researchers have focused on evaluating different pacing modes and algorithms to reduce the risk of AF during pacing. Catheter ablation may also be used as an alternative second-line therapy for some patients with SSS and AF.

Genetic insight into sick sinus syndrome.

AIMS: The aim of this study was to use human genetics to investigate the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development. METHODS AND RESULTS: We performed a genome-wide association study of 6469 SSS cases and 1 000 187 controls from deCODE genetics, the Copenhagen Hospital Biobank, UK Biobank, and the HUNT study. Variants at six loci associated with SSS, a reported missense variant in MYH6, known atrial fibrillation (AF)/electrocardiogram variants at PITX2, ZFHX3, TTN/CCDC141, and SCN10A and a low-frequency (MAF = 1.1-1.8%) missense variant, p.Gly62Cys in KRT8 encoding the intermediate filament protein keratin 8. A full genotypic model best described the p.Gly62Cys association (P = 1.6 × 10-20), with an odds ratio (OR) of 1.44 for heterozygotes and a disproportionally large OR of 13.99 for homozygotes. All the SSS variants increased the risk of pacemaker implantation. Their association with AF varied and p.Gly62Cys was the only variant not associating with any other arrhythmia or cardiovascular disease. We tested 17 exposure phenotypes in polygenic score (PGS) and Mendelian randomization analyses. Only two associated with the risk of SSS in Mendelian randomization, AF, and lower heart rate, suggesting causality. Powerful PGS analyses provided convincing evidence against causal associations for body mass index, cholesterol, triglycerides, and type 2 diabetes (P > 0.05). CONCLUSION: We report the associations of variants at six loci with SSS, including a missense variant in KRT8 that confers high risk in homozygotes and points to a mechanism specific to SSS development. Mendelian randomization supports a causal role for AF in the development of SSS.

Genetic insight into sick sinus syndrome.

AIMS: The aim of this study was to use human genetics to investigate the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development. METHODS AND RESULTS: We performed a genome-wide association study of 6469 SSS cases and 1 000 187 controls from deCODE genetics, the Copenhagen Hospital Biobank, UK Biobank, and the HUNT study. Variants at six loci associated with SSS, a reported missense variant in MYH6, known atrial fibrillation (AF)/electrocardiogram variants at PITX2, ZFHX3, TTN/CCDC141, and SCN10A and a low-frequency (MAF = 1.1-1.8%) missense variant, p.Gly62Cys in KRT8 encoding the intermediate filament protein keratin 8. A full genotypic model best described the p.Gly62Cys association (P = 1.6 × 10-20), with an odds ratio (OR) of 1.44 for heterozygotes and a disproportionally large OR of 13.99 for homozygotes. All the SSS variants increased the risk of pacemaker implantation. Their association with AF varied and p.Gly62Cys was the only variant not associating with any other arrhythmia or cardiovascular disease. We tested 17 exposure phenotypes in polygenic score (PGS) and Mendelian randomization analyses. Only two associated with the risk of SSS in Mendelian randomization, AF, and lower heart rate, suggesting causality. Powerful PGS analyses provided convincing evidence against causal associations for body mass index, cholesterol, triglycerides, and type 2 diabetes (P > 0.05). CONCLUSION: We report the associations of variants at six loci with SSS, including a missense variant in KRT8 that confers high risk in homozygotes and points to a mechanism specific to SSS development. Mendelian randomization supports a causal role for AF in the development of SSS.