Neonatal lupus erythematosus - practical guidelines.

BACKGROUND: Neonatal lupus erythematosus is an autoimmune disease acquired during fetal life as a result of transplacental passage of maternal anti-Sjögren's-syndrome-related antigen A (anti-SSA/Ro), anti-Sjögren's-syndrome-related antigen B (anti-SSB/La) or anti-U1 ribonucleoprotein (anti-U1-RNP) antinuclear autoantibodies. CONTENTS: Clinical manifestations include skin lesions, congenital heart block, hepatobiliary involvement and cytopenias. Most of the disorders disappear spontaneously after clearance of maternal antibodies. Cardiac symptoms, however, are not self-resolving and often pacemaker implantation is required. Diagnosis is based on clinical presentation and the presence of typical antibodies in the mother's or infant's serum. OUTLOOK: Neonatal lupus erythematosus may develop in children born to anti-SSA/Ro or anti-SSB/La women with various systemic connective tissue diseases. However, in half of the cases, the mother is asymptomatic, which may delay the diagnosis and have negative impact on the child's prognosis. Testing for antinuclear antibodies should be considered in every pregnant woman since early treatment with hydroxychloroquine or intravenous immunoglobulin (IVIG) has proven to be effective in preventing congenital heart block.

Electrocardiographic QT Intervals in Infants Exposed to Hydroxychloroquine Throughout Gestation.

BACKGROUND: Based on inhibition of viral replication and limited reports on clinical efficacy, hydroxychloroquine is being considered as prophylaxis and treatment of coronavirus disease-19 (COVID-19). Although hydroxychloroquine is generally considered safe during pregnancy based on studies in patients with systemic lupus erythematosus and other rheumatic conditions, there may still be reluctance to institute this antimalarial during pregnancy for the sole purpose of antiviral therapy. METHODS: To provide data regarding any potential fetal/neonatal cardiotoxicity, we leveraged a unique opportunity in which neonatal ECGs and hydroxychloroquine blood levels were available in a recently completed study evaluating the efficacy of hydroxychloroquine 400 mg daily to prevent the recurrence of congenital heart block associated with anti-SSA/Ro (anti-Sjögren's Syndrome A/Ro) antibodies. RESULTS: Forty-five ECGs were available for corrected QT interval (QTc) measurement, and levels of hydroxychloroquine were assessed during each trimester of pregnancy and in the cord blood, providing unambiguous assurance of drug exposure. Overall, there was no correlation between cord blood levels of hydroxychloroquine and the neonatal QTc (R=0.02, P=0.86) or the mean of hydroxychloroquine values obtained throughout each individual pregnancy and the QTc (R=0.04, P=0.80). In total 5 (11% [95% CI, 4%-24%]) neonates had prolongation of the QTc >2 SD above historical healthy controls (2 markedly and 3 marginally) but ECGs were otherwise normal. CONCLUSIONS: In aggregate, these data provide reassurances that the maternal use of hydroxychloroquine is associated with a low incidence of infant QTc prolongation. However, if included in clinical COVID-19 studies, early postnatal ECGs should be considered. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01379573.

Attenuating loss of cardiac conduction during no-flow ischemia through changes in perfusate sodium and calcium.

Myocardial ischemia leads to conduction slowing, cell-to-cell uncoupling, and arrhythmias. We previously demonstrated that varying perfusate sodium (Na+) and calcium (Ca2+) attenuates conduction slowing and arrhythmias during simulated ischemia with continuous perfusion. Cardioprotection was selectively associated with widening of the perinexus, a gap junction adjacent nanodomain important to ephaptic coupling. It is unknown whether perfusate composition affects the perinexus or ischemic conduction during nonsimulated ischemia, when coronary flow is reduced or halted. We hypothesized that altering preischemic perfusate composition could facilitate perinexal expansion and attenuate conduction slowing during global ischemia. To test this hypothesis, ex vivo guinea pig hearts (n = 49) were Langendorff perfused with 145 or 153 mM Na+ and 1.25 or 2.0 mM Ca2+ and optically mapped during 30 min of no-flow ischemia. Altering Na+ and Ca2+ did not substantially affect baseline conduction. Increasing Na+ and decreasing Ca2+ both lowered pacing thresholds, whereas increasing Ca2+ narrowed perinexal width (Wp). A least squares mean estimate revealed that reduced perfusate Na+ and Ca2+ resulted in the most severe conduction slowing during ischemia. Increasing Na+ alone modestly attenuated conduction slowing, yet significantly delayed the median time to conduction block (10 to 16 min). Increasing both Na+ and Ca2+ selectively widened Wp during ischemia (22.7 vs. 15.7 nm) and attenuated conduction slowing to the greatest extent. Neither repolarization nor levels of total or phosphorylated connexin43 correlated with conduction slowing or block. Thus, perfusate-dependent widening of the perinexus preserved ischemic conduction and may be an adaptive response to ischemic stress.NEW & NOTEWORTHY Conduction slowing during acute ischemia creates an arrhythmogenic substrate. We have shown that extracellular ionic concentrations can alter conduction by modulating ephaptic coupling. Here, we demonstrate increased extracellular sodium and calcium significantly attenuate conduction slowing during no-flow ischemia. This effect was associated with selective widening of the perinexus, an intercalated disc nanodomain and putative cardiac ephapse. These findings suggest that acute changes in ephaptic coupling may serve as an adaptive response to ischemic stress.

Visualization and quantification of the atrioventricular conduction axis in hearts with ventricular septal defect using phase contrast computed tomography.

OBJECTIVE: To visualize and quantify the atrioventricular conduction axis in the setting of ventricular septal defect using phase contrast computed tomography. METHODS: We used the SPring-8 synchrotron radiation facility in Hyogo prefecture in Japan, processing and reconstructing the data with 3-dimensional software. RESULTS: We studied 8 hearts obtained from patients known to have had ventricular septal defects, aged from 6 to 150 days, with a median of 24.5 days. None of the individuals, however, had undergone corrective surgery. The penetrating bundle was found at a median of 1.43 mm from the septal crest, with a range of 0.99 to 1.54 mm. The distance to the nonbranching bundle to the right ventricular endocardium was 1.10 mm, with a range from 0.49 to 2.49 mm, to the origin of the left bundle branch was 2.46 mm, with a range from 1.7 to 3.18 mm, and to the origin of the right bundle branch was 2.34 mm, with a range from 0.50 to 2.59 mm. The median distance from the edge of the caudal limb of the septomarginal trabeculation to the right bundle branch was 1.04 mm, with a range from 0.81 to 1.16 mm. CONCLUSIONS: We were able to show the precise location of the axis, with our findings suggesting that longitudinal sutures placed along the posteroinferior rim should be effective in avoiding iatrogenic injury, but sutures should not be placed in the valley between the limbs of the septomarginal trabeculation.

Transcatheter Closure of Perimembranous Ventricular Septal Defects Using Different Generations of Amplatzer Devices: Multicenter Experience.

OBJECTIVES: To demonstrate safety and efficacy of using different generations of softer Amplatzer™ devices for ventricular septal defect (VSD) closure to avoid serious complications at follow-up. BACKGROUND: Transcatheter closure of perimembranous ventricular septal defects (PmVSD) is a well-established procedure; however, it is associated with unacceptable incidence of complete heart block. Great advantages have been achieved by using softer devices for VSD transcatheter closure. The first and second generation of Amplatzer™ occluders (AVP II, ADO, and ADO II) seem to offer a safe and attractive alternative for this procedure. These devices can be delivered using either an arterial (retrograde) or venous (prograde) approach. METHODS AND RESULTS: Patients with congenital PmVSD who underwent transcatheter closure using ADO, ADO II, and AVP II devices were included. Primary end point was to determine efficacy and safety of these generations of devices and to determine the incidence of complications at follow-up (complete AV block and aortic/tricuspid/mitral regurgitation). One hundred and nineteen patients underwent VSD closure at a median age of 5 years (8 months-54 years). During the catheterization, there were only minor complications and at follow-up of 36 ± 25.7 months (up to 99 months), the closure rate was high of 98.3% and freedom from AV block was 100%. CONCLUSIONS: The use of softer Amplatzer™ devices is a good alternative to achieve PmVSD closure safely with no risk of AVB during the procedure or at midterm follow-up.

Systemic sarcoidosis presenting as complete heart block in a patient with normal chest radiography.

A previously healthy 44-year-old Caucasian man presented with recurrent syncope and was found to have a complete heart block with a ventricular rate of 24 bpm. No biochemical abnormalities were identified. Tick borne illnesses were ruled out. Paced echocardiogram revealed left ventricular systolic dysfunction with septal hypokinesis. Chest radiography and subsequent CT scan did not reveal adenopathy. However, a positron emission tomography scan demonstrated increased fluorodeoxyglucose uptake in the spleen, a right retro-clavicular lymph node, right ventricle and the interventricular septum of the heart. Excision biopsy of the retro-clavicular lymph node revealed non-caseating granulomas consistent with sarcoidosis. Complete heart block persisted despite steroid treatment. A pacemaker/biventricular implantable cardioverter defibrillator was placed for complete heart block and primary prevention of ventricular tachycardia and sudden cardiac death.

Hydroxychloroquine in obstetrics: New outlooks for therapy / La hidroxicloroquina en obstetricia. Nuevas perspectivas terapeuticas

Hydroxychloroquine is an antimalarial drug that is used to treat autoimmune diseases. It is safe in pregnancy and compatible with breastfeeding. Hydroxychloroquine is the drug of choice in pregnant women in need of treatment. Recently, it has proven useful for the treatment of refractory antiphospholipid syndrome and prevention of recurrence of congenital heart block in anti Ro/La-positive pregnant women. Two large prospective studies that will confirm the usefulness of this drug currently under way

La hidroxicloroquina es una droga antimalárica utilizada en enfermedades autoinmunes, segura en la gestación y en la lactancia, siendo la terapia de elección de mujeres gestantes que precisen tratamiento. Recientemente se ha visto su utilidad en el tratamiento del síndrome antifosfolipido refractario y en la prevención de la recurrencia del bloqueo cardiaco congénito en gestantes con anticuerpos antiRo/antiLa positivos. Están en marcha dos estudios prospectivos que confirmarán esta alternativa terapéutica

The prevention, screening and treatment of congenital heart block from neonatal lupus: a survey of provider practices.

Objective: To survey an international sample of providers to determine their current practices for the prevention, screening, and treatment of congenital heart block (CHB) due to maternal Ro/SSA antibodies. Methods: A survey was designed by the organizing committee of the 9th International Conference of Reproduction, Pregnancy and Rheumatic Diseases. It was sent to attendants of the conference and authors of recent publications or abstracts at ACR 2012, 2013 or 2014 on rheumatic diseases and pregnancy. Results: In anti-Ro/SSA positive women, 80% of 49 respondents recommended screening by serial fetal echocardiogram (ECHO), with most starting at week 16 (59%) and stopping at week 28 (25%), although the time to stop varied widely. For women without a prior infant with neonatal lupus, respondents recommend every other week (44%) or weekly (28%) fetal ECHOs. For women with a prior infant with neonatal lupus, 80% recommend weekly fetal ECHOs. To prevent CHB, HCQ was recommended by 67% of respondents and most would start pre-pregnancy (62%). Respondents were asked about medications to treat varying degrees of CHB in a 20-week pregnant, anti-Ro and La positive SLE patient. For first degree, respondents recommended starting dexamethasone (53%) or HCQ (43%). For second degree, respondents recommended starting dexamethasone (88%). For third degree, respondents recommended starting dexamethasone (55%) or IVIg (33%), although 27% would not start treatment. Conclusion: Despite the absence of official guidelines, many physicians with a focus on pregnancy and rheumatic disease have developed similar patterns in the screening, prevention and treatment of CHB.

Prenatal exposure to antimalarials decreases the risk of cardiac but not non-cardiac neonatal lupus: a single-centre cohort study.

Objective: Recent studies have suggested that prenatal exposure to HCQ reduces the risk of cardiac neonatal lupus. The aim of this study is to assess if maternal intake of antimalarials (AMs) throughout pregnancy lowered the risk of cardiac and non-cardiac neonatal lupus. Methods: Consecutive children seen between 1 January 1984 to 1 October 2013 born to women with a CTD and positive anti-Ro and/or anti-La antibodies were eligible for this single-centre retrospective cohort study. A total of 315 individuals were screened and 268 participants were included. Exposure to AMs was defined as HCQ or chloroquine throughout pregnancy. Outcomes were cardiac and non-cardiac neonatal lupus. Frequentist and Bayesian analyses were performed. We hypothesized that prenatal AM exposure would decrease the risk of cardiac but not non-cardiac neonatal lupus. Results: A total of 268 pregnancies were included; 73 were exposed to AMs throughout pregnancy. Ninety-nine children developed neonatal lupus, 117 remained unaffected and 52 children did not develop cardiac neonatal lupus but could not be categorized as unaffected since their full non-cardiac neonatal lupus status was unknown. Logistic regression suggested a protective effect of AM on cardiac neonatal lupus, but results were not statistically significant [odds ratio (OR) 0.21; P = 0.07]. Bayesian analysis showed that the probability of obtaining a protective effect (OR < 1.0) for cardiac neonatal lupus was significant (98.7%). The effect of AMs on non-cardiac neonatal lupus was not significant (OR 0.78; P = 0.21). Conclusion: In this large single-centre cohort study, exposure to AMs throughout pregnancy was associated with a decreased probability of developing cardiac but not non-cardiac neonatal lupus.

Progress in the pathogenesis and treatment of cardiac manifestations of neonatal lupus.

PURPOSE OF REVIEW: To provide new insights into pathogenesis, prevention and management of cardiac manifestations of neonatal lupus (cardiac neonatal lupus) and issues pertinent to all anti-SSA/Ro positive individuals of childbearing age. RECENT FINDINGS: Antibody specificity with high risk for cardiac neonatal lupus remains elusive, but high titers of Ro60, Ro52 or Ro52p200 antibodies appear to be required. Varying antibody specificities to the p200 region of Ro52 can induce first-degree block in a rodent model. In consideration of the contribution of macrophages to inflammation and fibrosis in cardiac neonatal lupus, hydroxychloroquine (HCQ) is being considered as preventive therapy. Cord blood biomarkers support the association of fetal reactive inflammatory and fibrotic components with the development and morbidity of cardiac neonatal lupus. Data from U.S. and French registries do not provide evidence that the prompt use of fluorinated steroids in cases of isolated block significantly alters fetal/neonatal morbidity or mortality. SUMMARY: The search for a high-risk cardiac neonatal lupus antibody profile remains, but high-titer antibodies to Ro60 and R052 are a consistent finding, and this may guide the need for fetal echocardiographic surveillance. The uniform use of fluorinated steroids to prevent progression of cardiac neonatal lupus or reduce mortality does not appear justified. HCQ, based on diminishing an inflammatory component of cardiac neonatal lupus, is under consideration as a potential preventive approach.

Ivabradine vs metoprolol in patients with acute inferior wall myocardial infarction-"Expanding arena for ivabradine".

BACKGROUND: Atrioventricular (AV) blocks are of concern with the use of beta blockers in inferior wall myocardial infarction (MI). Ivabradine lowers heart rate with a lesser risk of AV blocks. OBJECTIVES: To compare ivabradine with metoprolol in acute inferior wall MI in terms of feasibility, tolerability, and efficacy. METHODS: It was a prospective double-blind single-center randomized controlled study. Of 1032 patients with acute inferior wall MI, 468 eligible patients were randomized in 1:1 manner to ivabradine (group A) and metoprolol (group B). Intention to treat analysis of 426 patients (group A-232 and group B-232) was performed. The primary endpoint was 30-day incidence of major adverse cardiovascular events including death, reinfarction, complete heart block (CHB), and heart failure. Secondary endpoints included 30 days incidence of recurrent angina, readmission, first- or second-degree AV block, and tachyarrhythmias. RESULTS: Both the drugs decreased the mean heart rate to 62.22±2.95 (group A) vs 62.53±3.59 (group B) beats per minute (P=0.33). Ejection fraction improved in both the groups (5.15±1.93% in group A vs 5.52±2.18% in group B, P=0.065). The two groups did not differ significantly in their primary endpoints in terms of death (group A=1.72% vs group B=1.72%, OR=1.00, 95% CI=0.25-4.05, P=1.00), reinfarction (group A=0.86% vs group B=0.86%, OR=1.00, 95% CI=0.14-7.16, P=1.00), heart failure (group A=4.31% vs group B=2.59%, OR=1.70, 95% CI=0.61-4.75, P=0.31), or CHB (0% vs 2.59%, OR=0.07, 95% CI=0.00-1.34, P=0.08). There were no significant differences in the secondary endpoints of recurrent angina, readmission, and tachyarrhythmias except for more first- and second-degree AV blocks with metoprolol (12.93% vs 2.59%, OR=5.59, 95% CI=2.28-13.72, P=0.0002). CONCLUSIONS: Ivabradine is well tolerated and equally effective as metoprolol in acute inferior wall ST elevation myocardial infarction patients for lowering the heart rate with lesser risk of AV blocks.

Rapid pacing using the 0.035-in. Retrograde left ventricular support wire in 208 cases of transcatheter aortic valve implantation and balloon aortic valvuloplasty.

INTRODUCTION AND METHOD: Transcatheter aortic valve implantation (TAVI) and balloon aortic valvuloplasty (BAV) are now well established percutaneous procedures. These procedures almost always require bursts of rapid ventricular pacing to temporarily reduce cardiac output to facilitate the procedure, usually done via a temporary pacing wire inserted into the right ventricle. We describe a case series of 132 cases of TAVI and 76 BAV done using ventricular pacing via the left ventricular lead by simply connecting one electrode to the patient's skin and one electrode through the left ventricular (LV) wire. RESULTS: All of the 132 TAVI cases (a mixture of Edwards Sapien, Medtronic CoreValve and Boston Scientific Lotus) and 76 BAV were successfully performed using pacing through the LV wire. No BAV patients required temporary pacing wire (TPW) or permanent pacemaker (PPM) insertion. Of the TAVI patients, 6 (4.5%) required TPW during the procedure due to complete heart block to facilitate removal of the LV wire. 1 patient (0.8%) required a PPM urgently due to complete heart block and haemodynamic instability. Twenty eight Patients (21.2%) required PPM following TAVI, 9 of which were within the first 24 hr. Average time to pacemaker implantation was 3.7 days. CONCLUSION: Rapid ventricular pacing via the LV wire is a simple, safe and effective strategy for percutaneous aortic valve intervention and balloon aortic valvuloplasty. It eliminates the need for a temporary pacing wire with its attendant risks in the vast majority of cases. Furthermore, most pacemakers following TAVI are required late, after the first 24 hr period, by which time the TPW has already usually been removed. © 2016 Wiley Periodicals, Inc.

Long-Term Follow-Up of Children with Heart Block Born from Mothers with Systemic Lupus Erythematosus: A Retrospective Study from the Database Pediatric and Congenital Heart Disease in University Hospitals Leuven.

BACKGROUND: Children from mothers with systemic lupus erythematosus are frequently born with congenital heart block. This study aimed at evaluating long-term outcome because long-term data are scarce. METHODS: In the database of pediatric and congenital heart disease (University Hospitals Leuven), 19 children from systemic lupus erythematosus mothers and who were born with or developed atrioventricular block were identified. All records were reviewed for disease course and outcome. RESULTS: Median follow-up time was 7 years (interquartile ranges [IQR] 4.5-13 years). One child had no heart block at birth and developed only a first-degree block during follow-up. One had a second-degree heart block and developed a complete heart block. Seventeen patients (89%) were born with a complete heart block. Seventeen patients (89%) needed a definitive pacemaker. In all, epicardial leads were used at first implantation. Eighty-two percent received their pacemaker in the first year of life. The first battery had a median lifetime of 5 years (IQR 3.5-5 years), the second 6 years (IQR 4.5-6.3 years), and the third 5 years (IQR 5-6 years). Note that 47% of patients needed a lead replacement due to lead problems. Only one pericardial tamponade after pacemaker implantation. No device or lead infections occurred. The left ventricular systolic function at latest follow-up was normal for all. No patients died. CONCLUSION: In children with heart block born from systemic lupus erythematosus mothers, an early need for pacemaker implantation was documented. The overall battery life was acceptable, but there was a high need for lead replacement. Complication rate was low. Late outcome was good.

Fibrillatory excitation in the pulmonary vein is associated with the presence of dissociated pulmonary vein activity after isolation.

PURPOSE: Circumferential pulmonary vein (PV) isolation has been widely accepted for catheter ablation in patients with atrial fibrillation (AF). Dissociated PV activity might appear after PV isolation (PVI). However, little is known of dissociated PV activity. This study aimed to reveal the electrophysiological properties and clinical implications of dissociated PV activity. METHODS: The study subjects were 52 patients (62 ± 7 years, 38 men) who underwent PVI for AF. Electrophysiological properties of the left atrium (LA) and PVs during and after PVI were investigated. RESULTS: Out of 181 targeted PVs, 177 with successful isolation were analyzed. Dissociated PV activity appeared in 14 PVs (8 %) in 12 patients (23 %) after PVI; from the left superior PV in eight, right superior PV in five, and left inferior PV in one. The mean cycle length of dissociated PV activity was 4277 ± 2565 ms. The presence of AF prior to achieving PVI was significantly higher in PV without dissociated PV activity (105 out of 163, 64 %) than in PV with dissociated PV activity (five out of 14, 36 %, P = 0.03). The observed dissociated PV activity was enhanced (new appearance or reduced cycle length) by isoproterenol and suppressed by pacing within the isolated PV. CONCLUSION: Dissociated PV activity, although influenced by uncertain factors such as overdrive suppression and autonomic situations, would be an indicator of LA-PV bidirectional block and might not be the target of additional ablation after PVI.

Síndrome de Rosenbaum / Rosenbaum's syndrome

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