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1.
J Cardiovasc Electrophysiol ; 35(7): 1393-1400, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38741382

RESUMEN

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.


Asunto(s)
Ablación por Catéter , Frecuencia Cardíaca , Taquicardia Sinusal , Humanos , Femenino , Taquicardia Sinusal/cirugía , Taquicardia Sinusal/fisiopatología , Estudios Retrospectivos , Masculino , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Potenciales de Acción , Valor Predictivo de las Pruebas , Antiarrítmicos/uso terapéutico , Factores de Tiempo , Ultrasonografía Intervencional , Electrocardiografía Ambulatoria , Resistencia a Medicamentos , Nodo Sinoatrial/cirugía , Nodo Sinoatrial/fisiopatología , Ecocardiografía
2.
J Exp Biol ; 227(20)2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39221623

RESUMEN

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.


Asunto(s)
Evolución Biológica , Sistema de Conducción Cardíaco , Hemodinámica , Pericardio , Vertebrados , Animales , Pericardio/fisiología , Pericardio/embriología , Vertebrados/fisiología , Sistema de Conducción Cardíaco/fisiología , Corazón/fisiología , Corazón/embriología
3.
Europace ; 26(8)2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39120658

RESUMEN

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.


Asunto(s)
Algoritmos , Fibrilación Atrial , Estimulación Cardíaca Artificial , Anciano , Femenino , Humanos , Masculino , Fibrilación Atrial/terapia , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/mortalidad , Bloqueo Atrioventricular/diagnóstico , Bloqueo Atrioventricular/mortalidad , Bloqueo Atrioventricular/fisiopatología , Bloqueo Atrioventricular/terapia , Bradicardia/terapia , Bradicardia/prevención & control , Bradicardia/mortalidad , Bradicardia/diagnóstico , Estimulación Cardíaca Artificial/efectos adversos , Estimulación Cardíaca Artificial/métodos , Frecuencia Cardíaca , Ventrículos Cardíacos/fisiopatología , Hospitalización/estadística & datos numéricos , Marcapaso Artificial/efectos adversos , Factores de Riesgo , Resultado del Tratamiento , Función Ventricular Derecha
4.
Proc Natl Acad Sci U S A ; 118(1)2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-33443158

RESUMEN

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.


Asunto(s)
Factor de Transcripción GATA6/metabolismo , Frecuencia Cardíaca/fisiología , Nodo Sinoatrial/embriología , Animales , Arritmias Cardíacas/fisiopatología , Diferenciación Celular/genética , Factor de Transcripción GATA6/genética , Regulación del Desarrollo de la Expresión Génica/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Organogénesis , Nodo Sinoatrial/fisiología , Proteínas de Dominio T Box/genética
5.
Pediatr Cardiol ; 45(2): 441-445, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38145427

RESUMEN

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.


Asunto(s)
Bradicardia , Marcapaso Artificial , Humanos , Niño , Preescolar , Bradicardia/tratamiento farmacológico , Bradicardia/etiología , Estimulación Cardíaca Artificial/métodos , Marcapaso Artificial/efectos adversos , Síndrome del Seno Enfermo/tratamiento farmacológico , Síndrome del Seno Enfermo/complicaciones , Administración Oral
6.
Pediatr Cardiol ; 45(2): 361-367, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38062259

RESUMEN

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.


Asunto(s)
Estimulación Cardíaca Artificial , Ecocardiografía , Humanos , Estudios Prospectivos , Estimulación Cardíaca Artificial/métodos , Atrios Cardíacos/diagnóstico por imagen , Arritmias Cardíacas , Síndrome del Seno Enfermo
7.
Pediatr Cardiol ; 45(1): 63-67, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37740738

RESUMEN

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.


Asunto(s)
Cardiología , Procedimiento de Fontan , Cardiopatías Congénitas , Insuficiencia Cardíaca , Adulto , Niño , Humanos , Cardiopatías Congénitas/cirugía , Cardiopatías Congénitas/complicaciones , Arritmias Cardíacas/terapia , Arritmias Cardíacas/complicaciones , Encuestas y Cuestionarios , Insuficiencia Cardíaca/complicaciones
8.
Eur Heart J ; 44(40): 4246-4255, 2023 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-37638973

RESUMEN

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.
Artículo en Inglés | MEDLINE | ID: mdl-39408732

RESUMEN

(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.


Asunto(s)
Atrios Cardíacos , MicroARNs , ARN Mensajero , Nodo Sinoatrial , Factores de Transcripción , Humanos , MicroARNs/genética , Nodo Sinoatrial/metabolismo , Atrios Cardíacos/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica , Biología Computacional/métodos , Redes Reguladoras de Genes , Mitocondrias/genética , Mitocondrias/metabolismo , ARN Mitocondrial/genética , ARN Mitocondrial/metabolismo
10.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(1): 153-158, 2024 Jan 28.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-38615177

RESUMEN

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.


Asunto(s)
Hemodinámica , Litio , Humanos , Anticonvulsivantes , Arritmias Cardíacas/inducido químicamente , Sistema Nervioso Central
11.
Circulation ; 146(22): 1694-1711, 2022 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-36317529

RESUMEN

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.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Proteínas de Ciclo Celular , Humanos , Ratones , Animales , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas de Ciclo Celular/metabolismo , Factor de Crecimiento Transformador beta3/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Nodo Sinoatrial/metabolismo , Calcio/metabolismo , Canal Liberador de Calcio Receptor de Rianodina , Proteínas Serina-Treonina Quinasas/genética , Homeostasis , Fibrosis , Proliferación Celular , Proteínas Supresoras de Tumor
12.
Am J Physiol Heart Circ Physiol ; 324(3): H259-H278, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36563014

RESUMEN

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.


Asunto(s)
Síndrome del Seno Enfermo , Nodo Sinoatrial , Humanos , Anciano , Síndrome del Seno Enfermo/genética , Nodo Sinoatrial/metabolismo , Sistema de Conducción Cardíaco , Arritmias Cardíacas/metabolismo , Frecuencia Cardíaca/fisiología
13.
Catheter Cardiovasc Interv ; 102(4): 683-687, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37506123

RESUMEN

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.

14.
Cell Biol Toxicol ; 39(6): 2725-2741, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-36856942

RESUMEN

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.


Asunto(s)
Células Madre Pluripotentes Inducidas , Vía de Señalización Wnt , Humanos , Nodo Sinoatrial/metabolismo , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/metabolismo , Proteínas Morfogenéticas Óseas/metabolismo , Proteínas Morfogenéticas Óseas/farmacología , Diferenciación Celular
15.
Europace ; 26(1)2023 12 28.
Artículo en Inglés | MEDLINE | ID: mdl-38155611

RESUMEN

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.


Asunto(s)
Ablación por Catéter , Taquicardia Sinusal , Humanos , Taquicardia Sinusal/diagnóstico , Taquicardia Sinusal/cirugía , Taquicardia Sinusal/tratamiento farmacológico , Nodo Sinoatrial , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Frecuencia Cardíaca
16.
Europace ; 25(5)2023 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-36942949

RESUMEN

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.


Asunto(s)
Fibrilación Atrial , Insuficiencia Cardíaca , Marcapaso Artificial , Humanos , Femenino , Masculino , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Fibrilación Atrial/prevención & control , Estimulación Cardíaca Artificial/métodos , Incidencia , Resultado del Tratamiento , Marcapaso Artificial/efectos adversos , Síndrome del Seno Enfermo/terapia , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/prevención & control , Hospitalización
17.
Pacing Clin Electrophysiol ; 46(12): 1465-1471, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37910470

RESUMEN

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.


Asunto(s)
Bloqueo Atrioventricular , Marcapaso Artificial , Humanos , Síndrome del Seno Enfermo/terapia , Marcapaso Artificial/efectos adversos , Pacientes Ambulatorios , Hospitalización
18.
Pacing Clin Electrophysiol ; 46(7): 583-591, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37221975

RESUMEN

BACKGROUND: Bradyarrhythmias including sinus node dysfunction (SND) and atrioventricular block (AVB) can necessitate pacemaker (PPM) implantation in orthotopic heart transplant (OHT) recipients. Prior studies have shown conflicting findings regarding the effect of PPM implantation on survival. We evaluated the effect of PPM indication on long-term re-transplant-free survival in OHT patients. METHODS: We conducted a retrospective cohort study of OHT patients at UCLA Medical Center from 1985 to 2018. Indication for PPM (SND, AVB) was identified. Cox proportional hazards model with pacemaker implantation as a time-varying covariate was used to evaluate its effect on the primary endpoint of retransplant or death. We included 1609 OHTs in 1511 adult patients with median follow-up of 12 years. RESULTS: At transplant, patients were aged 53 ± 13 years and 1125 (74.5%) were male. Pacemakers were implanted in 109 (7.2%) patients; 65 for SND (4.3%) and 43 for AVB (2.8%). Repeat OHT was performed in 103 (6.4%) cases and 798 (52.8%) patients died during the follow-up period. The risk of the primary endpoint was significantly higher in patients requiring PPM for AVB (HR 3.0, 95% CI 2.1-4.2, p < .01) after controlling for age at OHT, gender, hypertension, diabetes, renal disease, history of repeat OHT, acute rejection, transplant coronary vasculopathy, and atrial fibrillation, but not PPM for SND (HR 1.0, 95% CI 0.70-1.4, p = 1.0). CONCLUSIONS: Patients who required PPM for AVB, but not SND, were at significantly higher risk of death or retransplant compared to patients who did not require PPM.


Asunto(s)
Fibrilación Atrial , Bloqueo Atrioventricular , Trasplante de Corazón , Marcapaso Artificial , Adulto , Humanos , Masculino , Femenino , Estudios Retrospectivos , Factores de Riesgo , Trasplante de Corazón/efectos adversos , Bloqueo Atrioventricular/terapia , Bloqueo Atrioventricular/etiología , Fibrilación Atrial/etiología , Síndrome del Seno Enfermo/terapia
19.
Pacing Clin Electrophysiol ; 46(7): 752-760, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37221974

RESUMEN

BACKGROUND: It is inevitable for patients to have a temporary or permanent pacemaker implanted during or after radiofrequency catheter ablation (RFCA) for treatment of atrial fibrillation (AF) in some cases. The aim of our study was to evaluate the incidence of pacemaker implantation (PMI) during or within 3 months of RFCA for AF and to identify the risk factors that were associated with PMI. METHODS: We performed a retrospective analysis of consecutive AF patients who underwent RFCA between August 2018 and October 2020 at our center. The incidence of PMI within 3 months during or after RFCA were assessed. A multivariate logistic regression model was performed to identify predictors of PMI. RESULTS: One thousand and five patients (mean age, 60.2 ± 10.3 years; 37.6% women) were included in this analysis. PVI was performed in all patients. A total of 23 (2.3%) patients had a pacemaker implanted within 3 months during or after ablation. Multivariable logistic regression analysis revealed that older age (OR: 1.08 [95% CI 1.03-1.13], p = .003), female sex (OR: 3.08 [95% CI 1.28-7.45], p = .012), paroxysmal AF (OR: 4.71 [95% CI 1.09-20.45], p = .038) and repeated ablation (OR: 2.78 [95% CI 1.04-7.40], p = .041) were the independent predictors for PMI. CONCLUSIONS: Older age, female sex, paroxysmal AF and repeated ablation were identified as predictive risk factors for PMI after RFCA in patients with AF. A "watch and wait" strategy could be taken for patients with temporary PMI after ablation, especially for those with prolonged sinus pause after AF termination.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Marcapaso Artificial , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Ablación por Catéter/efectos adversos , Recurrencia
20.
Pacing Clin Electrophysiol ; 46(8): 994-1002, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37319108

RESUMEN

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.


Asunto(s)
Bloqueo Atrioventricular , Marcapaso Artificial , Humanos , Bloqueo Atrioventricular/epidemiología , Bloqueo Atrioventricular/terapia , Bloqueo Atrioventricular/etiología , Bloqueo de Rama/terapia , Estudios de Seguimiento , Síndrome del Seno Enfermo/epidemiología , Síndrome del Seno Enfermo/terapia , Estudios Retrospectivos , Incidencia , Marcapaso Artificial/efectos adversos
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