Oral Albuterol Treatment in Three Pediatric Patients with Bradycardia: A Novel Therapy.

Clinically significant bradycardia is an uncommon problem in children, but one that can cause significant morbidity and sometimes necessitates implantation of a pacemaker. The most common causes of bradycardia are complete heart block (CHB), which can be congenital or acquired, and sinus node dysfunction, which is rare in children with structurally normal hearts. Pacemaker is indicated as therapy for the majority of children with CHB, and while early mortality is lower in postnatally diagnosed CHB than in fetal CHB, it is still up to 16%. In young children, less invasive transvenous pacemaker systems can be technically challenging to place and carry a high risk of complications, often necessitating surgical epicardial pacemaker placement, which usually entails a median sternotomy. We report three cases of pediatric patients referred for pacemaker implantation for different types of bradycardia, treated at our institution with oral albuterol with therapeutic results that avoided the need for surgical pacemaker implantation at that time.

[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.

[Reflex syncope-or more? : Ictal asystole!] / Reflexsynkope ­ oder mehr? : Iktale Asystolie!

A 59-year-old male patient was admitted for possible reflex syncope following loss of consciousness during urination. During the visit, a malaise with unconsciousness occurred. Holter ECG at that time showed increasing sinus bradycardia with transition to a junctional escape rhythm (30/min); in addition, there were several sinus pauses > 2.0 s (the longest almost 10 s). This malaise occurred again during routine EEG, when a focal epileptic seizure on the right fronto-temporal with sinus bradycardia after 15 s was documented. Thus, the diagnosis of ictal asystole was made, anticonvulsant therapy was started, and a cardiac pacemaker was implanted.

Effect of Shenfu Injection on Differentiation of Bone Marrow Mesenchymal Stem Cells into Pacemaker-Like Cells and Improvement of Pacing Function of Sinoatrial Node.

Sick sinus syndrome (SSS), a complex type of cardiac arrhythmia, is a major health threat to humans. Shenfu injection (SFI), a formula of traditional Chinese medicine (TCM), is effective in improving bradyarrhythmia. However, the underlying mechanism of SFI's therapeutic effect is subject to few systematic investigations. The purpose of the present research is to examine whether SFI can boost the differentiation effectiveness of bone marrow mesenchymal stem cells (BMSCs) into pacemaker-like cells and whether the transplantation of these cells can improve the pacing function of the sinoatrial node (SAN) in a rabbit model of SSS. BMSCs from New Zealand rabbits were extracted, followed by incubation in vitro. The flow cytometry was utilized to identify the expression of CD29, CD44, CD90, and CD105 surface markers. The isolated BMSCs were treated with SFI, and the whole-cell patch-clamp method was performed to detect hyperpolarization-the activated cyclic nucleotide-gated potassium channel 4 (HCN4) channel current activation curve. The SSS rabbit model was established using the formaldehyde wet dressing method, and BMSCs treated with SFI were transplanted into the SAN of the SSS rabbit model. We detected changes in the body-surface electrocardiogram and recorded dynamic heart rate measurements. Furthermore, transplanted SFI-treated BMSCs were subjected to HE staining, TUNEL staining, qPCR, western blotting, immunofluorescence, immunohistochemistry, and enzyme-linked immunosorbent assay to study their characteristics. Our results indicate that the transplantation of SFI-treated BMSCs into the SAN of SSS rabbits improved the pacing function of the SAN. In vitro data showed that SFI induced the proliferation of BMSCs, promoted their differentiation capacity into pacemaker-like cells, and increased the HCN4 expression in BMSCs. In vivo, the transplantation of SFI treated-BMSCs preserved the function of SAN in SSS rabbits, improved the expression of the HCN4 gene and gap junction proteins (Cx43 and Cx45), and significantly upregulated the expression of cAMP in the SAN, compared to the SSS model group. In summary, the present research demonstrated that SFI might enhance the differentiation capacity of BMSCs into pacemaker-like cells, hence offering a novel approach for the development of biological pacemakers. Additionally, we confirmed the effectiveness and safety of pacemaker-like cells differentiated from BMSCs in improving the pacing function of the SAN.

Yixin-Fumai granules improve sick sinus syndrome in aging mice through Nrf-2/HO-1 pathway: A new target for sick sinus syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Yixin-Fumai granules (YXFMs)-composed of Ginseng quinquefolium (L.) Alph. Wood, Ophiopogon japonicus (Thunb.) Ker Gawl, Schisandra arisanensis Hayata, Astragalus aaronsohnianus Eig, Salvia cryptantha Montbret & Aucher ex Benth, and Ligusticum striatum DC-are compound granules used in traditional Chinese medicine to increase heart rate and thus treat bradyarrhythmia. It may be effective in treating sick sinus syndrome (SSS). AIM: To observe the effect of YXFMs on aging-induced SSS in mice and explore whether this effect is related to the Nrf-2/HO-1 signaling pathway. MATERIALS AND METHODS: Mice with a significant decrease in the heart rate due to natural aging were selected to construct an SSS model. After the mice were administered YXFMs, the damage to their sinoartrial node (SAN) was assessed through electrocardiography, Masson's trichrome staining, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Dihydroethidium staining and immunofluorescence staining were used to assay reactive oxygen species (ROS) content and HCN4, respectively. Moreover, to observe the effects of YXFMs in vitro, the HL-1 cell line, derived from mouse atrial myocytes, was used to simulate SAN pacemaker cells, with H2O2 used as the cellular oxidative stress (OS) inducer. 2,7-Dichlorodihydrofluorescein diacetate staining was used to assay ROS content, whereas immunofluorescence staining and Western blotting were used to elucidate the related protein expression. Finally, mice were injected the Nrf-2 inhibitor ML385 to reversely verify the effects of YXFMs. RESULTS: In our in vivo experiments, YXFMs significantly inhibited aging-induced SSS, shortened the R-R interval, increased heart rate, alleviated fibrosis, reduced apoptosis rate and ROS content, and promote HCN4 expression in the SAN. In our in vitro experiments, YXFMs significantly inhibited H2O2-induced cell peroxidation damage, promoted Nrf-2 activation and nuclear metastasis, increased HO-1 expression- thereby inhibiting ROS accumulation-and finally, upregulated HCN4 expression through the inhibition of histone deacetylase 4 (HDAC4) expression and its nuclear metastasis. Finally, injection of the Nrf-2 inhibitor ML385 after YXFMs administration inhibited their protective effect in the mice. CONCLUSION: Here, we elaborated on the relationship between aging-induced SSS and the Nrf-2/HO-1 pathway for the first time and proposed that YXFMs improve SSS via the Nrf-2/HO-1 axis. Specifically, YXFMs promoted Nrf-2 activation and plasma-nuclear transfer to enhance HO-1 expression via the Nrf-2/HO-1 axis. This inhibited OS and reduced ROS accumulation in the SAN, and then, through the ROS/HDAC4 axis, reduced HDAC4 expression and plasma-nuclear transfer. Thereby, the OS-induced HCN4 loss in the SAN was inhibited-improving the function of If channel and thus producing SAN protection effect against SSS and improving the heart rate and R-R interval. In the future, we plan to use bioinformatics analysis technology to execute the next step of our research, namely to determine the effect of isolated, purified components of YXFMs in SSS, to increase its efficiency and reduce the toxicity of YXFMs.

Sinus Node Dysfunction due to Occlusion of the Sinus Node Artery during Percutaneous Coronary Intervention.

BACKGROUND: Sinus node artery occlusion (SNO) is a rare complication of percutaneous coronary intervention (PCI). We analyze both the short- and long-term consequences of SNO. METHODS: We retrospectively reviewed 1379 consecutive PCI's involving RCA and Cx arteries performed in our heart institute from 2016 to 2019. Median follow-up was 44 ± 5 months. RESULTS: Among the 4844 PCIs performed during the study period, 284 involved the RCA and the circumflex's proximal segment. Periprocedural SNO was estimated by angiography observed in 15 patients (5.3%), all originated from RCA. The majority of SNO occurred during urgent and primary PCIs following acute coronary syndrome (ACS). Sinus node dysfunction (SND) appeared in 12 (80%) of patients. Four (26.6%) patients had sinus bradycardia, which resolved spontaneously, and 8 (53.3%) patients had sinus arrest with an escaped nodal rhythm, which mostly responded to medical treatment during the first 24 hours. There was no association between PCI technique and outcome. Three patients (20%) required urgent temporary ventricular pacing. One patient had permanent pacemaker implantation. Pacemaker interrogation during follow-up revealed a recovery of the sinus node function after one month. CONCLUSION: SNO is rare and seen mostly during angioplasty to the proximal segment of the RCA during ACS. The risk of developing sinus node dysfunction following SNO is high. SND usually appears during the first 24 h of PCI. The majority of SND patients responded to medical treatment, and only in rare cases were permanent pacemakers required.

[Cilostazol and sick sinus syndrome]. / Efecto del cilostazol en la enfermedad del nodo sinusal.

Here we present the case of a 60-year-old patient with sinus node disease (NSS), symptomatic with dizziness and angor. The electrocardiogram showed episodes of sinus pauses with nodal escapes. During hospitalization, pending the placement of a definitive pacemaker, cilostazol (100 mg every 12 hours orally) was indicated, observing an increase in heart rate 48 hours after starting the medication, and the disappearance of sinus pauses in the 24 hours Holter. Our objective has been to show that cilostazol can be useful in patients with SNN, although long-term chronotropic effects of this treatment has yet to be evaluated.

Se presenta el caso de una paciente de 60 años con enfermedad del nodo sinusal (ENS), sintomática con mareos y ángor, con electrocardiograma que evidenciaba episodios de pausas sinusales con escapes nodales. Durante la internación, a la espera de colocación de marcapaso definitivo, se indicó cilostazol (100 mg cada 12 h vía oral), observando a las 48 horas del inicio un incremento en la frecuencia cardíaca y la desaparición de las pausas sinusales en Holter de 24 horas. Nue stro objetivo ha sido demostrar que el cilostazol puede ser útil en pacientes con ENS, aunque es necesario evaluar los efectos cronotrópicos a largo plazo de este tratamiento.

Positive chronotropic effects of theophylline and cilostazol in patients with symptomatic sick sinus syndrome who have declined permanent pacing.

Pacemakers are more commonly recommended than theophylline for sick sinus syndrome (SSS) treatment. The positive effects of cilostazol on bradyarrhythmias also have been reported. However, no comparison of cilostazol and theophylline has been previously reported found. We retrospectively enrolled SSS patients, who refused a pacemaker implantation. Theophylline or cilostazol was administered, and the heart rate (HR) was evaluated in 4-8 weeks using a digital sphygmomanometer and the electrocardiogram (ECG). A 200-400 mg of theophylline or 100-200 mg of cilostazol were administered per day in 50 and 30 patients, respectively. The baseline HR was 54.8 ± 13.5 beats per minute (bpm) on using sphygmomanometry and 51.9 ± 11.8 bpm using the ECG. In the theophylline group, the HR increased by 12.0 ± 16.3 bpm by sphygmomanometry (P < 0.001) and 8.4 ± 12.0 bpm by the ECG (P < 0.001). In the cilostazol group, the HR increased by 16.8 ± 13.9 bpm by sphygmomanometry (P < 0.001) and 12.4 ± 13.4 bpm using the ECG (P < 0.001). In 15 of the 50 theophylline patients, the medication was switched to cilostazol. The HR increased from 61.4 ± 13.8 bpm to 64.0 ± 12.6 bpm (P = 0.338). Symptoms such as dyspnea, chest discomfort, dizziness, and syncope significantly improved after the administration of the medications. There were no significant differences in the improvement in the symptoms except for dizziness between the two agents. Cilostazol was as effective as theophylline for increasing the HR in SSS patients.

Efecto del cilostazol en la enfermedad del nodo sinusal / Cilostazol and sick sinus syndrome

Resumen Se presenta el caso de una paciente de 60 años con enfermedad del nodo sinusal (ENS), sintomática con mareos y ángor, con electrocardiograma que evidenciaba episodios de pausas sinusales con escapes nodales. Durante la internación, a la espera de colocación de marcapaso definitivo, se indicó cilostazol (100 mg cada 12 h vía oral), observando a las 48 horas del inicio un incremento en la frecuencia cardíaca y la desaparición de las pausas sinusales en Holter de 24 horas. Nuestro objetivo ha sido demostrar que el cilostazol puede ser útil en pacientes con ENS, aunque es necesario evaluar los efectos cronotrópicos a largo plazo de este tratamiento.

Abstract Here we present the case of a 60-year-old patient with sinus node disease (NSS), symptomatic with dizziness and angor. The electrocardiogram showed episodes of sinus pauses with nodal escapes. During hospitalization, pending the placement of a definitive pacemaker, cilostazol (100 mg every 12 hours orally) was indicated, observing an increase in heart rate 48 hours after starting the medication, and the disappearance of sinus pauses in the 24 hours Holter. Our objective has been to show that cilostazol can be useful in patients with SNN, although long-term chronotropic effects of this treatment has yet to be evaluated.

"Preventive" pacing in patients with tachy-brady syndrome (TBS): Confirming a common practice.

AIMS: Many tachy-brady syndrome (TBS) patients, are implanted a permanent pacemaker (PPM) to allow continuation of anti-arrhythmic drug (AAD) therapy to maintain sinus rhythm. Many of these PPM's are implanted as a preventive measure, in absence of symptomatic bradycardia. Our primary aim was to evaluate pacing use among these patients and find predictors for PPM use. Our secondary aim was to appreciate the portion of these patients who progress to permanent atrial fibrillation (AF). METHODS: Retrospective study of TBS patients implanted a PPM as preventive measure, dividing cases into defined categories regarding highest percent atrial and ventricular pacing documented in PPM clinic visits during 3 year follow-up (F/U) period. Patients' baseline characteristics and AAD therapy were compared between cases with a major (>90%) pacing use and cases with <90% pacing use to find predictors for pacing use. Multivariable logistic regression was applied to identify independent variables associated with major pacing use. RESULTS: Our study included 119 TBS patients. Most (86.5%) TBS patients had a moderate (>50%) pacing use and 58% had a major pacing use. Significant association was found between pre-implant severe sinus bradycardia (<40 bpm), first degree atrioventricular block and amiodarone treatment to major pacing use on univariate analysis and severe sinus bradycardia was significantly associated with major pacing on multivariate analysis as well. Only minority (16.8%) of TBS patients progressed to permanent AF during the study F/U period. CONCLUSION: Our study reveals most TBS patients succeed to maintain sinus rhythm using an AAD with a significant pacing use, suggesting preventive PPM implantation might be advantageous in these cases. Pre-implant severe sinus bradycardia (<40 bpm) is a possible predictor for major pacing use in this population.

Renal failure, shock, and loss of pacemaker capture: A case of flecainide intoxication.

Flecainide intoxication is a severe intoxication that can lead to cardiogenic shock. We report on a 68-year-old female patient, who presented with a flecainide intoxication in the setting of renal failure. She was managed with invasive supportive therapy at the ICU and infusion of sodium bicarbonate and intravenous lipid emulsion (ILE, intralipid 20%), after which she made a complete recovery.

Clinical characteristics and outcome of lone atrial fibrillation at a tertiary referral centre: the Groote Schuur Hospital experience.

INTRODUCTION: Atrial fibrillation (AF) is a relatively common arrhythmia. When AF represents an electrophysiological phenomenon in structurally normal hearts, it is termed lone AF. This study was a retrospective, case-based analysis of patients attending the Cardiac Clinic at Groote Schuur Hospital (GSH) and describes the clinical characteristics and outcomes of patients classified as having lone atrial fibrillation. To the best of our knowledge there are no such studies reported from Africa. METHODS: This was a retrospective, descriptive study in which 289 medical records of patients with AF at the GSH Cardiac Clinic were reviewed from 1992 to 2006. The clinical data were interrogated to exclude identifiable causes of AF. Information on clinical characteristics and outcomes were entered into a data-entry form. Baseline descriptive statistics were expressed as means and range for continuous variables, and counts with percentages for categorical variables. RESULTS: Fifteen per cent (n = 42) of patients were identified as having lone AF, with a mean follow-up time of 5.8 years. Males comprised 57% (n = 24) and females 43% (n = 18). Fifty per cent (n = 21) of the patients had paroxysmal AF, 29% (n = 12) had persistent AF, and 12% (n = 5) progressed from paroxysmal to permanent AF. Subsets of lone AF included concomitant atrial flutter (17%) (n = 7) and sick sinus syndrome (21%) (n = 9). Complications were stroke (10%) (n = 4), tachycardia-related cardiomyopathy (17%) (n = 7) and bleeding complications on warfarin (11%) (n = 3). CONCLUSIONS: Lone AF is not an uncommon arrhythmia, with a preponderance in thin, middle-aged males. The symptoms of lone AF can be debilitating. It has associated morbidity, including tachycardia-related cardiomyopathy and thromboembolism. Rate control and appropriate anticoagulation are the cornerstones of patient management.

Hyperthyroidism and sick sinus syndrome, a rare but challenging association: A study of three cases.

Hyperthyroidism is usually associated with sinus tachycardia or supraventricular tachyarrhythmias, but rarely with dysfunction of the sinus node or other conduction disturbances. Evidence of bradyarrhythmia in patients with hyperthyroidism is clinically relevant, but the fact that several drugs with negative chronotropic effects (beta-blockers and calcium channel antagonists) are frequently used in the management of these patients must be taken into account. In the presence of sick sinus syndrome (SSS) or other conductance disturbances, therapy with agents that delay the activity of sinus node or atrioventricular conduction can lead to extreme bradycardia with syncope. In this paper, aspects of diagnosis and therapy in three patients with SSS and hyperthyroidism, admitted in the Clinic of Endocrinology or/and Cardiology of the County Hospital, Timisoara, have been presented.

Long term effects of cilostazol in a dog with sick sinus syndrome.

Sick sinus syndrome (SSS) is a type of bradyarrhythmia that can lead to syncope. Cilostazol has been reported to be an effective treatment for human patients with SSS and other bradyarrhythmias. This report describes the successful long-term treatment with cilostazol in a dog with SSS. A nine-year old intact male Miniature Schnauzer presented with a history of syncopal episodes and unsteady gait. After cilostazol treatment, the total heart rate (HR), mean HR, and frequency of premature ventricular contractions (PVCs) increased, while the maximum HR and maximum pause time decreased. Additionally, the number of syncopal episodes decreased. The dog died suddenly, 1,418 days after the start of cilostazol treatment. Cilostazol may be a useful therapeutic agent in canines with SSS.

Bradyarrhythmias: Clinical Presentation, Diagnosis, and Management.

Bradyarrhythmias are common clinical findings consisting of physiologic and pathologic conditions (sinus node dysfunction and atrioventricular [AV] conduction disturbances). Bradyarrhythmias can be benign, requiring no treatment; however, acute unstable bradycardia can lead to cardiac arrest. In patients with confirmed or suspected bradycardia, a thorough history and physical examination should include possible causes of sinoatrial node dysfunction or AV block. Management of bradycardia is based on the severity of symptoms, the underlying causes, presence of potentially reversible causes, presence of adverse signs, and risk of progression to asystole. Pharmacologic therapy and/or pacing are used to manage unstable or symptomatic bradyarrhythmias.

G protein-gated IKACh channels as therapeutic targets for treatment of sick sinus syndrome and heart block.

Dysfunction of pacemaker activity in the sinoatrial node (SAN) underlies "sick sinus" syndrome (SSS), a common clinical condition characterized by abnormally low heart rate (bradycardia). If untreated, SSS carries potentially life-threatening symptoms, such as syncope and end-stage organ hypoperfusion. The only currently available therapy for SSS consists of electronic pacemaker implantation. Mice lacking L-type Cav1.3 Ca(2+) channels (Cav1.3(-/-)) recapitulate several symptoms of SSS in humans, including bradycardia and atrioventricular (AV) dysfunction (heart block). Here, we tested whether genetic ablation or pharmacological inhibition of the muscarinic-gated K(+) channel (IKACh) could rescue SSS and heart block in Cav1.3(-/-) mice. We found that genetic inactivation of IKACh abolished SSS symptoms in Cav1.3(-/-) mice without reducing the relative degree of heart rate regulation. Rescuing of SAN and AV dysfunction could be obtained also by pharmacological inhibition of IKACh either in Cav1.3(-/-) mice or following selective inhibition of Cav1.3-mediated L-type Ca(2+) (ICa,L) current in vivo. Ablation of IKACh prevented dysfunction of SAN pacemaker activity by allowing net inward current to flow during the diastolic depolarization phase under cholinergic activation. Our data suggest that patients affected by SSS and heart block may benefit from IKACh suppression achieved by gene therapy or selective pharmacological inhibition.

Fetal and Neonatal Arrhythmias.

Cardiac arrhythmias are an important aspect of fetal and neonatal medicine. Premature complexes of atrial or ventricular origin are the main cause of an irregular heart rhythm. The finding is typically unrelated to an identifiable cause and no treatment is required. Tachyarrhythmia most commonly relates to supraventricular reentrant tachycardia, atrial flutter, and sinus tachycardia. Several antiarrhythmic agents are available for the perinatal treatment of tachyarrhythmias. Enduring bradycardia may result from sinus node dysfunction, complete heart block and nonconducted atrial bigeminy as the main arrhythmia mechanisms. The management and outcome of bradycardia depend on the underlying mechanism.

Sinus node dysfunction complicating viper bite.

Viper venom toxicities comprise mainly bleeding disorders and nephrotoxicity. Cardiotoxicity is a rare manifestation of viper bite. We describe the case of a previously healthy 35-year-old man who developed coagulopathy and sinus node dysfunction following a viper bite. Electrocardiography showed sinus arrest and junctional escape rhythm. This is the first account of sinus node dysfunction caused by a viper bite.