Norepinephrine mediates heart block during severe hypoglycemia in male rats.

Hypoglycemia is common in people with type 1 diabetes. Sometimes, severe hypoglycemia can be fatal. The underlying mechanisms by which severe hypoglycemia can lead to death are unclear. The sympathetic nervous system is thought to be proarrhythmic. We hypothesized that norepinephrine is the main mediator of severe hypoglycemia-induced fatal cardiac arrhythmias. To test this hypothesis, adult, non-diabetic Sprague-Dawley rats were subjected to hyperinsulinemic-severe hypoglycemic clamps (3 h, 10-15 mg/dL) during two different experiments: (1) intracerebroventricular (ICV) norepinephrine (n = 26) or artificial cerebrospinal fluid (aCSF) (n = 20) infusion or (2) blockade of norepinephrine release by intraperitoneal reserpine (n = 20) or control (n = 29). In experiment 1, brain norepinephrine infusion during severe hypoglycemia led to a 2.5-fold increase in third-degree heart block and a 24% incidence of ST elevation compared to no ST elevation in aCSF controls. In experiment 2, reserpine successfully reduced plasma and cardiac norepinephrine levels. During severe hypoglycemia, reserpine completely prevented second and third-degree heart block and T wave increases, a marker of myocardial infarction, compared to controls. In conclusion, norepinephrine increases while reserpine, used to reduce norepinephrine nerve terminal release, reduces heart block and markers of myocardial infarction during severe hypoglycemia.

Ischemic Heart Disease with In-Stent Re-Stenosis with Complete Heart Block and Isolated Persistent Left Superior Vena Cava - Rare Case Report with Challenges and Clinical Implications.

ABSTRACT: Isolated persistent left superior vena cava (PLSVC) is a very rare congenital thoracic venous system anomaly and is commonly an incidental finding, usually detected during central venous access, cardiac catheterization, or cardiothoracic surgeries. This is a rare case report wherein the patient is a known case of ischemic heart disease with s/p percutaneous transluminal coronary angioplasty (PTCA) with a stent to left anterior descending (LAD) artery with in-stent re-stenosis presented with complete heart block and had an unanticipated discovery of isolated PLSVC on facing difficulty during the transvenous approach of permanent pacemaker implantation (PPI). In this case report, we inspect the challenges associated with and various clinical implications of isolated PLSVC.

Stokes-Adams Syndrome as a Presenting Feature of Hypoadrenalism: A Rare Presentation.

Addison's disease is known to cause hyperkalemia. However, heart block as a result of such hyperkalemia is very rare. We report one such case where Addison's disease presented with hyperkalemia and resultant heart block and Stokes-Adam's syndrome along with other features of hypoadrenalism.

RésuméLa maladie d'Addison est connue pour provoquer une hyperkaliémie. Cependant, un bloc cardiaque résultant d'une telle hyperkaliémie est très rare. Nous rapportons un cas dans lequel la maladie d'Addison s'est accompagnée d'une hyperkaliémie et d'un bloc cardiaque et du syndrome de Stokes-Adam ainsi que d'autres caractéristiques d'hyposurrénalisme.

Systemic Diseases and Heart Block.

Systemic diseases can cause heart block owing to the involvement of the myocardium and thereby the conduction system. Younger patients (<60) with heart block should be evaluated for an underlying systemic disease. These disorders are classified into infiltrative, rheumatologic, endocrine, and hereditary neuromuscular degenerative diseases. Cardiac amyloidosis owing to amyloid fibrils and cardiac sarcoidosis owing to noncaseating granulomas can infiltrate the conduction system leading to heart block. Accelerated atherosclerosis, vasculitis, myocarditis, and interstitial inflammation contribute to heart block in rheumatologic disorders. Myotonic, Becker, and Duchenne muscular dystrophies are neuromuscular diseases involving the myocardium skeletal muscles and can cause heart block.

High-Degree Heart Block During Noncardiac Surgery Soon After Transcatheter Aortic Valve Replacement: A Case Report.

Patients undergoing transcatheter aortic valve replacement (TAVR) as a bridge to noncardiac surgery have improved outcomes. Older clinical trials concluded no increased risk of performing noncardiac surgery within 30 days of the TAVR procedure. Emerging evidence suggests patients with preexisting conduction abnormalities may require additional intervention to proceed safely with noncardiac surgery. More data are needed to clarify this clinical situation, especially for the anesthesiologist whose job is to mitigate risk for these patients. We present a patient who received a TAVR and suffered associated complications during subsequent surgery. We further discuss preventative measures and perioperative considerations for this patient population.

Transient pacing in pigs with complete heart block via myocardial injection of mRNA coding for the T-box transcription factor 18.

The adenovirus-mediated somatic transfer of the embryonic T-box transcription factor 18 (TBX18) gene can convert chamber cardiomyocytes into induced pacemaker cells. However, the translation of therapeutic TBX18-induced cardiac pacing faces safety challenges. Here we show that the myocardial expression of synthetic TBX18 mRNA in animals generates de novo pacing and limits innate and inflammatory immune responses. In rats, intramyocardially injected mRNA remained localized, whereas direct myocardial injection of an adenovirus carrying a reporter gene resulted in diffuse expression and in substantial spillover to the liver, spleen and lungs. Transient expression of TBX18 mRNA in rats led to de novo automaticity and pacemaker properties and, compared with the injection of adenovirus, to substantial reductions in the expression of inflammatory genes and in activated macrophage populations. In rodent and clinically relevant porcine models of complete heart block, intramyocardially injected TBX18 mRNA provided rate-adaptive cardiac pacing for one month that strongly correlated with the animal's sinus rhythm and physical activity. TBX18 mRNA may aid the development of biological pacemakers.

Molecular Mechanisms of Fetal and Neonatal Lupus: A Narrative Review of an Autoimmune Disease Transferal across the Placenta.

This study, conducted by searching keywords such as "maternal lupus", "neonatal lupus", and "congenital heart block" in databases including PubMed and Scopus, provides a detailed narrative review on fetal and neonatal lupus. Autoantibodies like anti-Ro/SSA and anti-La/SSB may cross the placenta and cause complications in neonates, such as congenital heart block (CHB). Management options involve hydroxychloroquine, which is able to counteract some of the adverse events, although the drug needs to be used carefully because of its impact on the QTc interval. Advanced pacing strategies for neonates with CHB, especially in severe forms like hydrops, are also assessed. This review emphasizes the need for interdisciplinary care by rheumatologists, obstetricians, and pediatricians in order to achieve the best maternal and neonatal health in lupus pregnancies. This multidisciplinary approach seeks to improve the outcomes and management of the disease, decreasing the burden on mothers and their infants.

Severe Tricuspid Regurgitation in a Patient with a Transvenous Dual-chamber Pacemaker: Considerations for Diagnosis and Management.

Cardiac implantable electronic device leads can contribute to tricuspid regurgitation and also complicate surgical and transcatheter interventions to manage tricuspid regurgitation. Here we present a case of a patient with sinus node dysfunction and complete heart block who underwent extraction of a right ventricular pacing lead before tricuspid valve surgery. We review the data regarding the contribution of leads to tricuspid regurgitation and the benefits of lead extraction, risks of jailing leads during tricuspid interventions, and pacing considerations around tricuspid valve procedures.

Home monitoring of fetal heart rhythm: Lived experiences of women with anti-SSA/Ro52 autoantibodies and their co-parents.

OBJECTIVE: The aim of this study was to explore the parents' experiences of home monitoring of the fetal heart rhythm. Women with anti-SSA/Ro52 autoantibodies carry a 2%-3% risk of giving birth to a child with congenital heart block (CHB), following transplacental transfer and antibody-mediated inflammation in the fetal conduction system during 18th to 24th gestational week. Early detection and subsequent treatment have been reported to decrease morbidity and mortality. Therefore, home monitoring of the fetal heart rhythm by Doppler has been offered at our fetal cardiology center. This study was undertaken to explore the lived experience of the routine. METHODS: Participants were recruited from a single fetal cardiology center. Consecutive sampling was used. The inclusion criteria were women with SSA/Ro52 antibodies who had undergone Doppler examinations within the last two and a half years at the hospital and had monitored the fetal heartbeat at home. A semi-structured questionnaire was created, and the participants were interviewed individually. The interviews were transcribed verbatim and analyzed according to qualitative content analysis. RESULTS: The overall theme was defined as "walking on thin ice," with six underlying categories: reality, different strategies, gain and loss, healthcare providers, underlying tension, and conducting the examinations again, all with a focus on how to handle the home monitoring during the risk period. CONCLUSION: Both the mother and the co-parent expressed confidence in their own abilities and that the monitoring provided them with the advantage of growing a bond with the expected child. However, all the participants described a feeling of underlying tension during the risk period. The results show that home monitoring is not experienced as complicated or a burden for the parents-to-be and should be considered a vital part of the chain of care for mothers at risk for giving birth to a child with CHB. However, explaining the teamwork between the different caregivers, for the patients involved, their areas of expertise, and how they collaborate with the patient continues to be a pedagogic challenge and should be developed further.

Vericiguat suppresses ventricular tachyarrhythmias inducibility in a rabbit myocardial infarction model.

BACKGROUND: The VICTORIA trial demonstrated a significant decrease in cardiovascular events through vericiguat therapy. This study aimed to assess the potential mechanisms responsible for the reduction of cardiovascular events with vericiguat therapy in a rabbit model of myocardial infarction (MI). METHODS: A chronic MI rabbit model was created through coronary artery ligation. Following 4 weeks, the hearts were harvested and Langendorff perfused. Subsequently, electrophysiological examinations and dual voltage-calcium optical mapping studies were conducted at baseline and after administration of vericiguat at a dose of 5 µmol/L. RESULTS: Acute vericiguat therapy demonstrated a significant reduction in premature ventricular beat burden and effectively suppressed ventricular arrhythmic inducibility. The electrophysiological influences of vericiguat therapy included an increased ventricular effective refractory period, prolonged action potential duration, and accelerated intracellular calcium (Cai) homeostasis, leading to the suppression of action potential and Cai alternans. The pacing-induced ventricular arrhythmias exhibited a reentrant pattern, attributed to fixed or functional conduction block in the peri-infarct zone. Vericiguat therapy effectively mitigated the formation of cardiac alternans as well as the development of reentrant impulses, providing additional anti-arrhythmic benefits. CONCLUSIONS: In the MI rabbit model, vericiguat therapy demonstrates anti-ventricular arrhythmia effects. The vericiguat therapy reduces ventricular ectopic beats, inhibiting the initiation of ventricular arrhythmias. Furthermore, the therapy successfully suppresses cardiac alternans, preventing conduction block and, consequently, the formation of reentry circuits.

Prevalence of neonatal lupus in a small group of antibody-carrying mothers and frequency of complete atrioventricular block.

BACKGROUND: Neonatal lupus (NL) is extremely rare and is caused by the transplacental passage of maternal IgG autoantibodies against Ro, La, and/or RNP proteins into the fetal circulation, which can cause congenital complete atrioventricular block (CCAB), permanent skin lesions, and liver involvement. OBJECTIVE: To know the prevalence of NL in patients with CCAB and the clinical course in long-term follow-up. METHODS: From January 1992 to December 2017, patients with CCAB were included. The presence of anti-SSA/Ro and anti-SSB/La antinuclear antibodies in maternal serum confirmed NL. RESULTS: Eight patients were included with a follow-up of 10 ± 6 years; NL was concluded in 62.5%; two were male. One of them was diagnosed in utero, two at birth, and a pacemaker was implanted in them, one at 12 years of age and another at 15. The other two cases were diagnosed at 18 and 26 years of age, and permanent pacemakers were implanted 8 and 5 years later, respectively. In one case, a definitive pacemaker was not implanted in a newborn with only 1 year of follow-up. At delivery, 60% of the mothers were free of rheumatic disease, and altogether, they all had 19 children; none of them presented NL manifestations. CONCLUSIONS: CCAB is rare and frequently associated with a maternal autoimmune disease, practically all of them will require a definitive pacemaker at some point in their lives.

ANTECEDENTES: El lupus neonatal (LN) es extremadamente raro y es ocasionado por el paso transplacentario de auto-anticuerpos maternos IgG contra las proteínas Ro, La y/o RNP a la circulación fetal que puede ocasionar bloqueo aurículo-ventricular completo congénito (BAVCC) permanente, lesiones dérmicas y afectación hepática. OBJETIVO: Conocer la prevalencia de LN en paciente con BAVCC y la evolución clínica en un seguimiento a largo plazo. MÉTODOS: De enero de 1992 a diciembre 2017 se incluyeron paciente con BAVCC. La presencia de anticuerpos antinucleares anti-SSA/Ro y anti-SSB/La en suero materno confirmó LN. RESULTADOS: Ocho pacientes fueron incluidos con seguimiento de 10 ± 6 años, el 62.5 % con LN; dos fueron del sexo masculino. Uno diagnosticado in útero, dos al nacimiento, en ellos se implantó marcapaso; uno a los 12 años de edad y otro a los 15. Los otros dos casos fueron diagnosticados a los 18 y 26 años, se implantó marcapaso definitivo en ellos 8 y 5 años después respectivamente. En un caso no se implantó marcapaso definitivo; un recién nacido con solo un año de seguimiento. Al dar a luz, el 60 % de las madres estaban libres de enfermedad reumática y en conjunto todas tuvieron 19 hijos, ninguno de ellos presentó manifestaciones de LN. CONCLUSIONES: El BAVCC es raro y frecuentemente está asociado a una enfermedad autoinmune materna, prácticamente todos requerirán de marcapaso definitivo en alguna época de su vida.

Subclinical maternal autoimmune disease leading to congenital high degree atrioventricular block: Case report and review of the literature.

Maternal autoimmune disease is the most common cause of congenital heart block (CHB), a rare illness characterized by fibrosis and calcification of the fetal atrioventricular (AV) node due to maternal autoantibodies anti-SSA/Ro and anti-SSB/La. We report the full autopsy and clinical information on a female neonate with high degree AV block and calcification in the AV node, atrial approaches to the AV node, and both right and left bundle branches, born to a 27-year-old female with subclinical autoimmune disease.

Can prolonged P-R interval predict clinical outcomes in non-ST elevation acute coronary syndrome patients?

BACKGROUND: The present study aimed to respond to clinical question, can prolonged P-R interval predict clinical outcomes in non-ST elevation acute coronary syndrome patients? METHODS: This descriptive-analytical study was conducted on cardiac patients. All of the non-ST elevation acute coronary syndrome (NSTEACS) including non-ST elevation myocardial infarction (NSTEMI) and unstable angina patients included in the study. Then they divided into two groups: prolonged P-R interval and normal P-R interval. The patients who had a history of digoxin and calcium channel blocker use, using antiarrhythmic drugs, known valvular or congenital heart disease and connective tissue, unreadable P-R interval and cardiac block were excluded. Data were collected using the questionnaire consisted demographic data and clinical outcomes and a follow-up part was completed by one of the researchers. RESULTS: Finally, 248 patients completed the study. The results showed both of the two groups had significant differences in terms of the history of myocardial infarction (MI) (p = 0.018), the level of high-density lipoprotein (HDL) (p = 0.004), heart rate (p = 0.042), inverted T wave (p = 0.017), anterior ST- segment depression (p = 0.008), normal report of coronary angiography (CAG) (p = 0.003), three vessels disease (p = 0.043), left main lesion (p = 0.045) and SYNTAX score (p = 0.032) based on the CAG report. The results of six-month follow-up showed although, the frequency of ischemic stroke, coronary artery disease (CAD) and cardiovascular death were higher in prolonged P-R interval groups. The chi-square test showed this difference was statistically non-significant (p > 0.05). The multivariate logistic regression model revealed non-significant relationships between prolonged P-R interval and SYNTAX score, significant CAD, three-vessel disease, inverted T wave, anterior ST depression, heart rate and HDL. CONCLUSIONS: Based on the results of our study the six-month follow-up showed non-significant outcomes. Further studies are recommended to assess the long-term outcomes.

Boerhaave's Syndrome Presenting in the Setting of Third-Degree Heart Block.

Introduction: Boerhaave's syndrome, or the spontaneous transmural perforation of the esophagus, is typically thought to be due to an increase in esophageal pressure such as that which occurs during vomiting or retching. Another common etiology of esophageal perforation is esophageal instrumentation, such as during esophagogastroduodenoscopy or transesophageal echocardiography. This life-threatening condition requires prompt diagnosis and treatment to prevent patient demise. While a history of vomiting can aid in diagnosis, this history can be difficult to elicit in an unconscious patient or may be altogether absent. Additionally, Boerhaave's syndrome can present similarly to more common upper gastrointestinal or cardiac conditions. Since mortality increases with delays in diagnosis and treatment, it is imperative that clinicians maintain a high level of suspicion for Boerhaave's syndrome and initiate treatment urgently. Case Description: This report presents a 76-year-old man who presented to the emergency department after a history of several syncopal episodes and was found to be in complete heart block. Two days later, he acutely developed abdominal distention and coffee ground emesis. As the medical team was able to gather more history from the patient and his family, it was revealed that he had associated vomiting with his episodes of syncope. CT scan of the abdomen and pelvis demonstrated pneumomediastinum concerning for esophageal perforation. His clinical status subsequently deteriorated. He was intubated and a temporary transvenous pacer was placed before being transferred to our facility for emergent surgery. Discussion: Complete heart block in the setting of Boerhaave's syndrome is exceptionally rare, with only 2 cases reported in the literature. The decision to place a pacemaker in the setting of esophageal perforation/sepsis is complicated and depends on the patient's bacteremia status related to noncardiac comorbidities. Clearly this case represents the need for excellent multidisciplinary decision-making processes with excellent communication between hospital staff and all caretakers. Expeditious diagnosis and treatment of esophageal perforation is essential to prevent leaking of gastric contents into the mediastinum and worsening of cardiac complications and sepsis. Additionally, critical timing of various surgical procedures, especially the need for a permanent pacemaker implant with bacteremia is a complicated process not well described in the surgical literature.

Case report: Cardiac arrest after radiofrequency ablation in a 76-year-old male.

RATIONALE: Previous studies have found that the main treatment of sinus arrest is pacemaker treatment. It is rare to have 12 s of sinus arrest after radiofrequency ablation, and whether a permanent pacemaker is implanted immediately in this case is not described in the guidelines. PATIENT CONCERNS: A 76-year-old male patient with persistent atrial fibrillation (AF) developed sinus arrest lasting 12 s in the early morning of the fourth day after using radiofrequency ablation for pulmonary vein isolation. DIAGNOSIS: The patient was diagnosed with AF and sinus arrest. INTERVENTIONS: The patient received cardiopulmonary resuscitation, intravenous injection of atropine 1 mg, and intravenous infusion of isoproterenol 1mg and immediately recovered consciousness thereafter. Approximately, 1.5 h later, the patient underwent surgery to install a temporary pacemaker in the right femoral vein. OUTCOMES: The patient had repeated episodes of sinus arrest after the implantation of a temporary pacemaker. After 3 weeks, the patient stabilized and was discharged. The patient was followed up for 1 year and did not experience any recurrence of sinus arrest or AF. LESSONS: We consider the potential for postoperative myocardial edema, injury to the sinoatrial node during the procedure, propafenone poisoning, and autonomic dysfunction as contributors to the occurrence of sinus arrest after radiofrequency ablation. When sinus arrest occurs after radiofrequency ablation, we can choose the appropriate treatment according to the patient's condition.

Newborns with congenital complete heart block: Advice for perinatal care providers.

Congenital complete heart block (CCHB) is a rare, but a potentially life-threatening manifestation of autoimmune diseases in neonates. Bradycardia in CCHB can be misdiagnosed as foetal distress in utero and thus precipitating a Caesarean section. We report a case series of three neonates with bradycardia without any electrolyte abnormalities and structurally normal hearts with favourable outcomes.