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1.
J Cardiovasc Electrophysiol ; 35(7): 1393-1400, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38741382

RESUMO

INTRODUCTION: Inappropriate sinus tachycardia (IST) is a common condition with frequently not tolerated beta-blockers or ivabradine and a high rate of complication in ablation strategy; we describe an alternative anatomical approach of sinus node (SN) modulation. METHODS: This retrospective study describes a case series of 6 patients from two centers diagnosed with symptomatic IST undergoing SN ablation. RESULTS: The mean age was 40.6 ± 13.9 years; five of the six patients were female, 100% of patients reported heart palpitations, and 66% reported dizziness, the average heart rate (HR) on a 24-h Holter was 93.2 ± 7.9 bpm. HR during the first stage of a stress test using a standard Bruce protocol was 150 ± 70 bpm, The average HR on 24-h Holter postablation was 75 ± 5.6 bpm, the sinus rate HR during stage 1 of a Bruce protocol exercise stress test was 120 ± 10 bpm. CONCLUSION: This is the first case series reporting the acute and long-term results of a novel anatomical approach for SN modulation to treat IST targeting the arcuate ridge (AR) under intracardiac echography (ICE) guidance. The novel anatomic ICE-guided catheter ablation approach aimed to identify the earliest activation at the AR with an extension of RF lesions toward its septal region seems effective and safe to modulate the SN in symptomatic patients with IST refractory to medical treatment.


Assuntos
Ablação por Cateter , Frequência Cardíaca , Taquicardia Sinusal , Humanos , Feminino , Taquicardia Sinusal/cirurgia , Taquicardia Sinusal/fisiopatologia , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Potenciais de Ação , Valor Preditivo dos Testes , Antiarrítmicos/uso terapêutico , Fatores de Tempo , Ultrassonografia de Intervenção , Eletrocardiografia Ambulatorial , Resistência a Medicamentos , Nó Sinoatrial/cirurgia , Nó Sinoatrial/fisiopatologia , Ecocardiografia
2.
J Exp Biol ; 227(20)2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39221623

RESUMO

Development of the heart is a very intricate and multiplex process as it involves not only the three spatial dimensions but also the fourth or time dimension. Over time, the heart of an embryo needs to adapt its function to serve the increasing complexity of differentiation and growth towards adulthood. It becomes even more perplexing by expanding time into millions of years, allocating related species in the tree of life. As the evolution of soft tissues can hardly be studied, we have to rely on comparative embryology, supported heavily by genetic and molecular approaches. These techniques provide insight into relationships, not only between species, but also between cell populations, signaling mechanisms, molecular interactions and physical factors such as hemodynamics. Heart development depends on differentiation of a mesodermal cell population that - in more derived taxa - continues in segmentation of the first and second heart field. These fields deliver not only the cardiomyocytes, forming the three-dimensionally looping cardiac tube as a basis for the chambered heart, but also the enveloping epicardium. The synchronized beating of the heart is then organized by the conduction system. In this Review, the epicardium is introduced as an important player in cardiac differentiation, including the conduction system.


Assuntos
Evolução Biológica , Sistema de Condução Cardíaco , Hemodinâmica , Pericárdio , Vertebrados , Animais , Pericárdio/fisiologia , Pericárdio/embriologia , Vertebrados/fisiologia , Sistema de Condução Cardíaco/fisiologia , Coração/fisiologia , Coração/embriologia
3.
Europace ; 26(8)2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39120658

RESUMO

AIMS: Physiological activation of the heart using algorithms to minimize right ventricular pacing (RVPm) may be an effective strategy to reduce adverse events in patients requiring anti-bradycardia therapies. This systematic review and meta-analysis aimed to evaluate current evidence on clinical outcomes for patients treated with RVPm algorithms compared to dual-chamber pacing (DDD). METHODS AND RESULTS: We conducted a systematic search of the PubMed database. The predefined endpoints were the occurrence of persistent/permanent atrial fibrillation (PerAF), cardiovascular (CV) hospitalization, all-cause death, and adverse symptoms. We also aimed to explore the differential effects of algorithms in studies enrolling a high percentage of atrioventricular block (AVB) patients. Eight studies (7229 patients) were included in the analysis. Compared to DDD pacing, patients using RVPm algorithms showed a lower risk of PerAF [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.57-0.97] and CV hospitalization (OR 0.77, 95% CI 0.61-0.97). No significant difference was found for all-cause death (OR 1.01, 95% CI 0.78-1.30) or adverse symptoms (OR 1.03, 95% CI 0.81-1.29). No significant interaction was found between the use of the RVPm strategy and studies enrolling a high percentage of AVB patients. The pooled mean RVP percentage for RVPm algorithms was 7.96% (95% CI 3.13-20.25), as compared with 45.11% (95% CI 26.64-76.38) of DDD pacing. CONCLUSION: Algorithms for RVPm may be effective in reducing the risk of PerAF and CV hospitalization in patients requiring anti-bradycardia therapies, without an increased risk of adverse symptoms. These results are also consistent for studies enrolling a high percentage of AVB patients.


Assuntos
Algoritmos , Fibrilação Atrial , Estimulação Cardíaca Artificial , Idoso , Feminino , Humanos , Masculino , Fibrilação Atrial/terapia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/mortalidade , Bloqueio Atrioventricular/diagnóstico , Bloqueio Atrioventricular/mortalidade , Bloqueio Atrioventricular/fisiopatologia , Bloqueio Atrioventricular/terapia , Bradicardia/terapia , Bradicardia/prevenção & controle , Bradicardia/mortalidade , Bradicardia/diagnóstico , Estimulação Cardíaca Artificial/efeitos adversos , Estimulação Cardíaca Artificial/métodos , Frequência Cardíaca , Ventrículos do Coração/fisiopatologia , Hospitalização/estatística & dados numéricos , Marca-Passo Artificial/efeitos adversos , Fatores de Risco , Resultado do Tratamento , Função Ventricular Direita
4.
Proc Natl Acad Sci U S A ; 118(1)2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33443158

RESUMO

The sinus node (SAN) is the primary pacemaker of the human heart, and abnormalities in its structure or function cause sick sinus syndrome, the most common reason for electronic pacemaker implantation. Here we report that transcription factor GATA6, whose mutations in humans are linked to arrhythmia, is highly expressed in the SAN and its haploinsufficiency in mice results in hypoplastic SANs and rhythm abnormalities. Cell-specific deletion reveals a requirement for GATA6 in various SAN lineages. Mechanistically, GATA6 directly activates key regulators of the SAN genetic program in conduction and nonconduction cells, such as TBX3 and EDN1, respectively. The data identify GATA6 as an important regulator of the SAN and provide a molecular basis for understanding the conduction abnormalities associated with GATA6 mutations in humans. They also suggest that GATA6 may be a potential modifier of the cardiac pacemaker.


Assuntos
Fator de Transcrição GATA6/metabolismo , Frequência Cardíaca/fisiologia , Nó Sinoatrial/embriologia , Animais , Arritmias Cardíacas/fisiopatologia , Diferenciação Celular/genética , Fator de Transcrição GATA6/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Organogênese , Nó Sinoatrial/fisiologia , Proteínas com Domínio T/genética
5.
Pediatr Cardiol ; 45(2): 441-445, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38145427

RESUMO

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.


Assuntos
Bradicardia , Marca-Passo Artificial , Humanos , Criança , Pré-Escolar , Bradicardia/tratamento farmacológico , Bradicardia/etiologia , Estimulação Cardíaca Artificial/métodos , Marca-Passo Artificial/efeitos adversos , Síndrome do Nó Sinusal/tratamento farmacológico , Síndrome do Nó Sinusal/complicações , Administração Oral
6.
Pediatr Cardiol ; 45(1): 63-67, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37740738

RESUMO

Sinus node dysfunction with concomitant junctional rhythm (JR) is frequently observed among Fontan patients and has been recognized as a contributor to heart failure. The impact and management of JR is unclear. A survey was mailed to all members of the Pediatric and Congenital Electrophysiology society (PACES) and members were asked to forward the questionnaire to their non-electrophysiology colleagues. Responses were received from 154 physicians (88 electrophysiologists (EP's) and 66 non-EP's (46 pediatric cardiologists and 20 adult congenital cardiologists). There were few differences in the response between EP's and non-EP's. Overall, 57% recommended an annual ambulatory ECG (AECG). A significant majority (80%) opted to continue to follow patients with significant periods of JR on AECG as long as the patients were asymptomatic, and showed no echocardiographic signs of cardiac decompensation. However, 84% would place a pacemaker in a patient with JR who was having open chest surgery for other reasons. Finally, pacemaker placement would be performed by 91% if a patient with JR showed signs of heart failure. Most congenital cardiologists would not recommend pacemaker placement in asymptomatic Fontan patients with JR. Further studies are needed on the Fontan population to determine the impact of SND and JR on longer term outcomes and to determine the role and optimal timing of pacemaker placement in these patients.


Assuntos
Cardiologia , Técnica de Fontan , Cardiopatias Congênitas , Insuficiência Cardíaca , Adulto , Criança , Humanos , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/complicações , Arritmias Cardíacas/terapia , Arritmias Cardíacas/complicações , Inquéritos e Questionários , Insuficiência Cardíaca/complicações
7.
Pediatr Cardiol ; 45(2): 361-367, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38062259

RESUMO

Sinus node dysfunction (SND) with junctional rhythm (JR) is common after the Fontan operation. Atrial pacing (AP) restores atrioventricular (AV) synchrony, but the placement of a pacemaker carries significant morbidity. To study the impact of AP on echocardiographic parameters of function in Fontan patients with SND and JR. Nine Fontan patients with AP for SND and JR were prospectively studied with echocardiography in the following conditions-baseline paced rhythm, underlying JR and, if possible, slow-paced rhythm below their baseline paced rate (~ 10 bpm faster than their JR rate). Cardiac index was significantly lower in JR (3 ± 1.1 L/min/m2) vs AP (4.2 ± 1.4 L/min/m2; p = 0.002). Diastolic function also significantly worsened with increased ratio of early diastolic systemic AV valve inflow velocity to early diastolic systemic AV valve annulus velocity (E/e' ratio) by tissue Doppler imaging (TDI) in JR (11.6 ± 4.6) vs AP (8.8 ± 2.2, p = 0.016). Pulmonary venous flow reversal was present in 7/9 patients in JR vs 0/9 in AP (p = 0.016). There were no significant differences in these echocardiographic measurements between the paced and slow-paced conditions. When compared to AP, JR was associated with a significant reduction in cardiac output and diastolic function, and an increased prevalence of pulmonary vein flow reversal. There were no differences between paced and slow-paced conditions, suggesting that AV synchrony rather than heart rate was primarily contributing to cardiac output. Further studies are needed to understand the chronic impact of JR on Fontan outcomes.


Assuntos
Estimulação Cardíaca Artificial , Ecocardiografia , Humanos , Estudos Prospectivos , Estimulação Cardíaca Artificial/métodos , Átrios do Coração/diagnóstico por imagem , Arritmias Cardíacas , Síndrome do Nó Sinusal
8.
Eur Heart J ; 44(40): 4246-4255, 2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37638973

RESUMO

BACKGROUND AND AIMS: High percentages of atrial pacing have been associated with an increased risk of atrial fibrillation. This study is aimed at evaluating whether atrial pacing minimization in patients with sinus node dysfunction reduces the incidence of atrial fibrillation. METHODS: In a nationwide, randomized controlled trial, 540 patients with sinus node dysfunction and an indication for first pacemaker implantation were assigned to pacing programmed to a base rate of 60 bpm and rate-adaptive pacing (DDDR-60) or pacing programmed to a base rate of 40 bpm without rate-adaptive pacing (DDD-40). Patients were followed on remote monitoring for 2 years. The primary endpoint was time to first episode of atrial fibrillation longer than 6 min. Secondary endpoints included longer episodes of atrial fibrillation, and the safety endpoint comprised a composite of syncope or presyncope. RESULTS: The median percentage of atrial pacing was 1% in patients assigned to DDD-40 and 49% in patients assigned to DDDR-60. The primary endpoint occurred in 124 patients (46%) in each treatment group (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.76-1.25, P = .83). There were no between-group differences in atrial fibrillation exceeding 6 or 24 h, persistent atrial fibrillation, or cardioversions for atrial fibrillation. The incidence of syncope or presyncope was higher in patients assigned to DDD-40 (HR 1.71, 95% CI 1.13-2.59, P = .01). CONCLUSIONS: Atrial pacing minimization in patients with sinus node dysfunction does not reduce the incidence of atrial fibrillation. Programming a base rate of 40 bpm without rate-adaptive pacing is associated with an increased risk of syncope or presyncope.

9.
Int J Mol Sci ; 25(19)2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39408732

RESUMO

(1) Background: The sinus node (SN) is the main pacemaker of the heart. It is characterized by pacemaker cells that lack mitochondria and contractile elements. We investigated the possibility that transcription factors (TFs) and microRNAs (miRs) present in the SN can regulate gene expression that affects SN morphology and function. (2) Methods: From human next-generation sequencing data, a list of mRNAs that are expressed at lower levels in the SN compared with the right atrium (RA) was compiled. The mRNAs were then classified into contractile, mitochondrial or glycogen mRNAs using bioinformatic software, RStudio and Ingenuity Pathway Analysis. The mRNAs were combined with TFs and miRs to predict their interactions. (3) Results: From a compilation of the 1357 mRNAs, 280 contractile mRNAs and 198 mitochondrial mRNAs were identified to be expressed at lower levels in the SN compared with RA. TFs and miRs were shown to interact with contractile and mitochondrial function-related mRNAs. (4) Conclusions: In human SN, TFs (MYCN, SOX2, NUPR1 and PRDM16) mainly regulate mitochondrial mRNAs (COX5A, SLC25A11 and NDUFA8), while miRs (miR-153-3p, miR-654-5p, miR-10a-5p and miR-215-5p) mainly regulate contractile mRNAs (RYR2, CAMK2A and PRKAR1A). TF and miR-mRNA interactions provide a further understanding of the complex molecular makeup of the SN and potential therapeutic targets for cardiovascular treatments.


Assuntos
Átrios do Coração , MicroRNAs , RNA Mensageiro , Nó Sinoatrial , Fatores de Transcrição , Humanos , MicroRNAs/genética , Nó Sinoatrial/metabolismo , Átrios do Coração/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica , Biologia Computacional/métodos , Redes Reguladoras de Genes , Mitocôndrias/genética , Mitocôndrias/metabolismo , RNA Mitocondrial/genética , RNA Mitocondrial/metabolismo
10.
Artigo em Inglês | MEDLINE | ID: mdl-39426459

RESUMO

INTRODUCTION: Pediatric patients with congenital heart disease repair may develop sinus node dysfunction. Leadless pacemakers have provided an alternative option to transvenous and epicardial device implants for pediatric patients in need of ventricular pacing. We describe the first adolescent patient to receive a leadless pacemaker in the atrium due to symptomatic sinus pauses. METHODS: The study was approved by the internal review board of the University of California at Davis. Femoral vein implant was performed of an Aveir VR due to the higher impedance and larger battery capacity. RESULTS: The 16-year-old male with dextro-transposition of the great arteries and ventricular septal defect repair had an uncomplicated atrial appendage implant of an Atrial Aveir VR, under transesophageal echocardiographic guidance. Three-month follow-up demonstrated stable threshold of 0.5 V @ 0.2 milliseconds, impedance of 720 Ω and sensing of 9.1 mV, with 10 % pacing and predicted battery longevity of 22.8 years. CONCLUSION: Atrial implant of a leadless pacemaker is possible in the older pediatric population without complications, including of the Aveir VR.

11.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(1): 153-158, 2024 Jan 28.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-38615177

RESUMO

Bipolar affective disorder refers to a category of mood disorders characterized clinically by the presence of both manic or hypomanic episodes and depressive episodes. Lithium stands out as the primary pharmacological intervention for managing bipolar affective disorder. However, its therapeutic dosage closely approaches toxic levels. Toxic symptoms appear when the blood lithium concentration surpasses 1.4 mmol/L, typically giving rise to gastrointestinal and central nervous system reactions. Cardiac toxicity is rare but serious in cases of lithium poisoning. The study reports a case of a patient with bipolar affective disorder who reached a blood lithium concentration of 6.08 mmol/L after the patient took lithium carbonate sustained-release tablets beyond the prescribed dosage daily and concurrently using other mood stabilizers. This resulted in symptoms such as arrhythmia, shock, impaired consciousness, and coarse tremors. Following symptomatic supportive treatment, including blood dialysis, the patient's physical symptoms gradually improved. It is necessary for clinicians to strengthen the prevention and recognition of lithium poisoning.


Assuntos
Hemodinâmica , Lítio , Humanos , Anticonvulsivantes , Arritmias Cardíacas/induzido quimicamente , Sistema Nervoso Central
12.
Circulation ; 146(22): 1694-1711, 2022 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-36317529

RESUMO

BACKGROUND: The sinoatrial node (SAN) functions as the pacemaker of the heart, initiating rhythmic heartbeats. Despite its importance, the SAN is one of the most poorly understood cardiac entities because of its small size and complex composition and function. The Hippo signaling pathway is a molecular signaling pathway fundamental to heart development and regeneration. Although abnormalities of the Hippo pathway are associated with cardiac arrhythmias in human patients, the role of this pathway in the SAN is unknown. METHODS: We investigated key regulators of the Hippo pathway in SAN pacemaker cells by conditionally inactivating the Hippo signaling kinases Lats1 and Lats2 using the tamoxifen-inducible, cardiac conduction system-specific Cre driver Hcn4CreERT2 with Lats1 and Lats2 conditional knockout alleles. In addition, the Hippo-signaling effectors Yap and Taz were conditionally inactivated in the SAN. To determine the function of Hippo signaling in the SAN and other cardiac conduction system components, we conducted a series of physiological and molecular experiments, including telemetry ECG recording, echocardiography, Masson Trichrome staining, calcium imaging, immunostaining, RNAscope, cleavage under targets and tagmentation sequencing using antibodies against Yap1 or H3K4me3, quantitative real-time polymerase chain reaction, and Western blotting. We also performed comprehensive bioinformatics analyses of various datasets. RESULTS: We found that Lats1/2 inactivation caused severe sinus node dysfunction. Compared with the controls, Lats1/2 conditional knockout mutants exhibited dysregulated calcium handling and increased fibrosis in the SAN, indicating that Lats1/2 function through both cell-autonomous and non-cell-autonomous mechanisms. It is notable that the Lats1/2 conditional knockout phenotype was rescued by genetic deletion of Yap and Taz in the cardiac conduction system. These rescued mice had normal sinus rhythm and reduced fibrosis of the SAN, indicating that Lats1/2 function through Yap and Taz. Cleavage Under Targets and Tagmentation sequencing data showed that Yap potentially regulates genes critical for calcium homeostasis such as Ryr2 and genes encoding paracrine factors important in intercellular communication and fibrosis induction such as Tgfb1 and Tgfb3. Consistent with this, Lats1/2 conditional knockout mutants had decreased Ryr2 expression and increased Tgfb1 and Tgfb3 expression compared with control mice. CONCLUSIONS: We reveal, for the first time to our knowledge, that the canonical Hippo-Yap pathway plays a pivotal role in maintaining SAN homeostasis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Ciclo Celular , Humanos , Camundongos , Animais , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ciclo Celular/metabolismo , Fator de Crescimento Transformador beta3/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Nó Sinoatrial/metabolismo , Cálcio/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina , Proteínas Serina-Treonina Quinases/genética , Homeostase , Fibrose , Proliferação de Células , Proteínas Supressoras de Tumor
13.
Am J Physiol Heart Circ Physiol ; 324(3): H259-H278, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36563014

RESUMO

The sinoatrial node (SAN) is the primary pacemaker of the heart. Normal SAN function is crucial in maintaining proper cardiac rhythm and contraction. Sinus node dysfunction (SND) is due to abnormalities within the SAN, which can affect the heartbeat frequency, regularity, and the propagation of electrical pulses through the cardiac conduction system. As a result, SND often increases the risk of cardiac arrhythmias. SND is most commonly seen as a disease of the elderly given the role of degenerative fibrosis as well as other age-dependent changes in its pathogenesis. Despite the prevalence of SND, current treatment is limited to pacemaker implantation, which is associated with substantial medical costs and complications. Emerging evidence has identified various genetic abnormalities that can cause SND, shedding light on the molecular underpinnings of SND. Identification of these molecular mechanisms and pathways implicated in the pathogenesis of SND is hoped to identify novel therapeutic targets for the development of more effective therapies for this disease. In this review article, we examine the anatomy of the SAN and the pathophysiology and epidemiology of SND. We then discuss in detail the most common genetic mutations correlated with SND and provide our perspectives on future research and therapeutic opportunities in this field.


Assuntos
Síndrome do Nó Sinusal , Nó Sinoatrial , Humanos , Idoso , Síndrome do Nó Sinusal/genética , Nó Sinoatrial/metabolismo , Sistema de Condução Cardíaco , Arritmias Cardíacas/metabolismo , Frequência Cardíaca/fisiologia
14.
Catheter Cardiovasc Interv ; 102(4): 683-687, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37506123

RESUMO

Covered stent correction of a superior sinus venosus atrial septal defect is increasingly performed as an alternative to surgical repair. While sinus node dysfunction requiring pacemaker implantation may be required after surgical repair, this has not been previously reported after covered stent implantation. We reviewed the experience in two interventional centers. Balloon inflation in the superior vena cava was used to confirm the anomalous pulmonary vein drainage would be unobstructed after stent implantation. During balloon testing in 62 consecutive patients, we assessed gradients across the pulmonary vein to left atrium while monitoring the rhythm. We observed the outcomes after covered stent correction in 51 patients. In a single patient, significant bradycardia and pauses developed on repeat balloon testing and the procedure was abandoned without stent implantation. In another patient, there was no sign of sinus node dysfunction during balloon testing but several hours after stent implantation, the patient became symptomatic from sinus bradycardia and pauses and had a pacemaker implanted 3 days later. Over a year later there are some signs of improvement in sinus node function. While sinus node dysfunction has not been described previously during balloon testing or after stent implantation, this report demonstrates for the first time that it may occur. Larger registries are therefore required to monitor for this uncommon complication.

15.
Cell Biol Toxicol ; 39(6): 2725-2741, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36856942

RESUMO

The embryonic development of sinus nodes (SAN) is co-regulated by multiple signaling pathways. Among these, the bone morphogenetic protein (BMP) and Wnt signaling pathways are involved in the development of SAN. In this study, the effects of BMP and Wnt signaling on the differentiation of SAN-like pacemaker cells (SANLPCs) were investigated. Human induced pluripotent stem cells (hiPSCs) were divided into four groups: control, BMP4, CHIR-3, and BMP4 + CHIR (CHIR: a Wnt signaling activator). The samples were tested at day (D) 15 of differentiation. The final protocol for the activation of BMP signaling at D0-D3 and reactivation of Wnt signaling at D5-D7 in the differentiation of hiPSCs were determined. The results showed that the mRNA levels of pacemaker markers (TBX18, SHOX2, TBX3, HCN4, and HCN1) were higher in the BMP4 + CHIR group than in the control group, and working myocardial genes were downregulated. The immunofluorescence assay revealed that the expression of SHOX2 and HCN4 increased in the BMP4 + CHIR group compared to that in the other groups. In addition, the results of patch clamps revealed that a funny current of higher density and typical SAN action potentials were recorded, except in the control group, in which the L-type calcium current was higher in the BMP4 + CHIR group than in the other groups. Finally, the proportion of SANLPCs (cTnT+ NKX2.5-) was further enhanced by the combination of BMP4 and CHIR treatment. In summary, the combination of BMP and Wnt signaling promotes the differentiation of SANLPCs from hiPSCs.


Assuntos
Células-Tronco Pluripotentes Induzidas , Via de Sinalização Wnt , Humanos , Nó Sinoatrial/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas Morfogenéticas Ósseas/farmacologia , Diferenciação Celular
16.
Europace ; 26(1)2023 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-38155611

RESUMO

AIMS: A novel sinus node (SN) sparing hybrid ablation for inappropriate sinus node tachycardia (IST)/postural orthostatic tachycardia syndrome (POTS) has been demonstrated to be an effective and safe therapeutic option in patients with symptomatic drug-resistant IST/POTS. The aim of this study was to evaluate the long-term rate of redo procedures after hybrid IST ablation and procedural strategy, outcomes and safety of redo procedures. METHODS AND RESULTS: All consecutive patients from 2015 to 2023 were prospectively enrolled in the UZ Brussel monocentric IST/POTS registry. They were analysed if the following inclusion criteria were fulfilled: 1) diagnosis of IST or POTS, 2) symptomatic IST/POTS refractory or intolerant to drugs, and 3) hybrid SN sparing ablation performed. The primary endpoint was redo procedure. The primary safety endpoint was pacemaker (PM) implantation. A total of 220 patients undergone to hybrid IST ablation were included, 185 patients (84.1%) were treated for IST and 61 patients (27.7%) for POTS.After a follow-up of 73.3 ± 16.2 months, 34 patients (15.4%) underwent a redo. A total of 23 patients (67.6%) had a redo for IST recurrence and 11 patients (32.4%) for other arrhythmias. Pacemaker implantation was performed in 21 patients (9.5%). Nine patients (4.1%) had no redo procedure and experienced sick sinus syndrome requiring a PM. Twelve patients (5.4%) received a PM as a shared therapeutic choice combined with SN ablation procedure. CONCLUSION: In a large cohort of patients the long-term free survival from redo procedure after hybrid IST ablation was 84.6% with a low PM implantation rate.


Assuntos
Ablação por Cateter , Taquicardia Sinusal , Humanos , Taquicardia Sinusal/diagnóstico , Taquicardia Sinusal/cirurgia , Taquicardia Sinusal/tratamento farmacológico , Nó Sinoatrial , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Frequência Cardíaca
17.
Europace ; 25(5)2023 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-36942949

RESUMO

AIMS: In bradycardia patients treated with dual-chamber pacing, we aimed to evaluate whether pacing with atrioventricular (AV) delay management [AV hysteresis (AVH)], compared with standard pacing with fixed AV delays, reduces unnecessary ventricular pacing percentage (VPP) and is associated with better clinical outcomes. Main study endpoints were the incidence of heart failure hospitalizations (HFH), persistent atrial fibrillation (AF), and cardiac death. METHODS AND RESULTS: Data from two identical prospective observational studies, BRADYCARE I in the USA and BRADYCARE II in Europe, Africa, and Asia, were pooled. Overall, 2592 patients (75 ± 10 years, 45.1% female, 50% with AVH) had complete clinical and device data at 1-year follow-up and were analysed. Primary pacing indication was sinus node disease (SND) in 1177 (45.4%), AV block (AVB) in 974 (37.6%), and other indications in 441 (17.0%) patients. Pacing with AVH, compared with standard pacing, was associated with a lower 1-year incidence of HFH [1.3% vs. 3.1%, relative risk reduction (RRR) 57.5%, P = 0.002] and of persistent AF (5.3% vs. 7.7%, RRR = 31.1%, P = 0.028). Cardiac mortality was not different between groups (1.0% vs. 1.4%, RRR = 27.8%, P = 0.366). Pacing with AVH, compared with standard pacing, was associated with a lower (P < 0.001) median VPP in all patients (7% vs. 75%), in SND (3% vs. 44%), in AVB (25% vs. 98%), and in patients with other pacing indications (3% vs. 47%). CONCLUSION: Cardiac pacing with AV delay management via AVH is associated with reduced 1-year incidence of HFH and persistent AF, most likely due to a reduction in VPP compared to standard pacing.


Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Marca-Passo Artificial , Humanos , Feminino , Masculino , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/prevenção & controle , Estimulação Cardíaca Artificial/métodos , Incidência , Resultado do Tratamento , Marca-Passo Artificial/efeitos adversos , Síndrome do Nó Sinusal/terapia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/prevenção & controle , Hospitalização
18.
Pacing Clin Electrophysiol ; 46(7): 705-709, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36450154

RESUMO

The selection of patients with chronotropic incompetence (CI) for cardiac pacing therapy remains challenging. Here, we present a case of a 40-year-old woman with severe exertional dyspnea. The exercise test revealed a blunted increase in the heart rate (HR) (maximum of 110 bpm). Her exercise capacity significantly improved under atrial stimulation at 170 bpm using a temporary pacing lead. Therefore, we implanted a rate-adaptive dual-chamber pacemaker with a blended sensor. During follow-up exercise capacity normalized, and she had no residual exertional dyspnea at 6 months. This case highlights the potential value for individual assessments of CI to identify clear indications for pacemaker implantation.


Assuntos
Marca-Passo Artificial , Humanos , Feminino , Adulto , Arritmias Cardíacas/tratamento farmacológico , Frequência Cardíaca/fisiologia , Estimulação Cardíaca Artificial , Átrios do Coração , Antiarrítmicos/uso terapêutico
19.
Pacing Clin Electrophysiol ; 46(12): 1465-1471, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37910470

RESUMO

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.


Assuntos
Bloqueio Atrioventricular , Marca-Passo Artificial , Humanos , Síndrome do Nó Sinusal/terapia , Marca-Passo Artificial/efeitos adversos , Pacientes Ambulatoriais , Hospitalização
20.
Pacing Clin Electrophysiol ; 46(8): 994-1002, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37319108

RESUMO

BACKGROUND: A pacemaker implantation is not indicated in cases of reversible high-degree symptomatic sinus node dysfunction (SND) and atrioventricular block (AVB). However, it remains uncertain whether these reversible automaticity/conduction disorders may recur in some patients at follow-up, in the absence of reversible cause. This retrospective study aimed to determine the incidence and predictive factors of permanent pacemaker (PPM) implantation at follow-up and after reversible high-degree SND/AVB. METHODS: Based on medical electronic files codes, we identified patients who were hospitalized in our cardiac intensive care unit between January 2003 and December 2020 due to reversible high-degree SND/AVB and who were discharged from the hospital alive and without PPM implantation. Acute myocardial infarction and post-cardiac surgery patients were excluded. We categorized the patients according to the need for PPM at follow-up due to non-reversible high-degree SND/AVB. RESULTS: Of the 93 patients included, 26 patients (28%) were readmitted for PPM implantation at follow-up after hospital discharge. Among baseline characteristics, compared with patients who did not have high-degree SND/AVB recurrence, those who had subsequent PPM implantation had less frequent previous hypertension (70% vs. 46%, p = .031). Regarding the initial causes of reversible SND/AVB, isolated hyperkalemia was found more often in the patients readmitted for PPM (19% vs. 3% vs. p = .017). Moreover, recurrence of high-degree SND/AVB was significantly associated with the presence of intraventricular conduction disorders (either bundle branch block or left bundle branch hemiblock) on ECG at discharge (36% in patients without PPM vs. 68% in PPM patients, p = .012). CONCLUSION: Almost one third of the patients discharged alive from the hospital after a reversible high-degree SND/AVB needed a pacemaker implantation at follow-up. Complete bundle branch block or left bundle branch hemiblock on discharge ECG after recovery of atrioventricular conduction and/or sinus automaticity was associated with a greater risk of recurrence leading to pacemaker implantation.


Assuntos
Bloqueio Atrioventricular , Marca-Passo Artificial , Humanos , Bloqueio Atrioventricular/epidemiologia , Bloqueio Atrioventricular/terapia , Bloqueio Atrioventricular/etiologia , Bloqueio de Ramo/terapia , Seguimentos , Síndrome do Nó Sinusal/epidemiologia , Síndrome do Nó Sinusal/terapia , Estudos Retrospectivos , Incidência , Marca-Passo Artificial/efeitos adversos
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