Surveillance and Treatment to Prevent Fetal Atrioventricular Block Likely to Occur Quickly (STOP BLOQ)

监测和治疗以预防胎儿房室传导阻滞可能很快发生（STOP BLOQ）

• 批准号: 10250529
• 负责人: Jill P Buyon
• 金额: $ 72.48万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10250529
• 关键词: Address; Anti-Inflammatory Agents; Antibody titer measurement; Atrioventricular Block; Autoantibodies; Biological Process; Birth; Bradycardia; Clinical; Colorado; Data; Detection; Dexamethasone; Disease; Early treatment; Echocardiography; Educational process of instructing; Electrocardiogram; Endocardial Fibroelastosis; Ensure; Equipoise; Event; Extranodal; Feedback; Fetal Heart Rate; Fetal Monitoring; Fetus; Fibrosis; Frequencies; Guidelines; Health Benefit; Healthcare; Heart; Heart Diseases; Heart Injuries; Home; Hour; IgG Receptors; Incidence; Inflammation; Inflammatory; Intravenous Immunoglobulins; Mediating; Monitor; Morbidity - disease rate; Mothers; Multicenter Trials; Myocardial dysfunction; National Institute of Child Health and Human Development; Natural History; Outcome; Participant; Pathogenesis; Perinatal mortality demographics; Phase; Placebos; Placenta; Pregnancy; Public Health; Registries; Reporting; Research; Research Personnel; Risk; Sample Size; Second Pregnancy Trimester; Site; Survivors; System; Techniques; Testing; Universities; Woman; arm; cardiac pacing; disability; effusion; evidence base; falls; fetal; heart rhythm; interdisciplinary collaboration; medical schools; millisecond; mortality; network models; novel; prenatal; prenatal testing; prevent; primary outcome; programs; prospective; recruit; rheumatologist; screening; side effect; standard of care; support network; time interval

ABSTRACT Fetal complete (i.e., 3°) atrioventricular block (AVB), identified in the 2nd trimester in an otherwise normally developing heart, is almost universally associated with maternal anti-Ro autoantibodies and carries a high morbidity and mortality. It has been speculated that full expression of conduction disease results in orderly progression from normal rhythm (NR) to 1° AVB [prolonged AV interval assessed by echocardiogram (echo)], to 2° AVB (irregular cardiac rhythm or bradycardia), culminating in 3° AVB. Identification of a transition period, marked by an irregular rhythm and/or bradycardia, may be the only window of opportunity for treatment to restore NR. Thus, current surveillance employing weekly echos would fall short. We have now shown that daily fetal heart rate and rhythm monitoring (FHRM) by the mother with confirmation of abnormal findings by echo is feasible and affords rapid and successful treatment with no cases of AVB missed. The proposal combines expertise of fetal cardiologist Bettina F. Cuneo, MD (University of Colorado–Denver), rheumatologist Jill P. Buyon, MD (NYU School of Medicine), and 33 sites, to address the hypotheses that early treatment is critical, FHRM reduces the need for weekly echos, and surveillance can be limited to mothers with high-titer antibodies. This prospective trial involves three sequential Steps: 1) Screening for high titer anti-Ro60 or Ro52 centrally in Dr. Buyon's lab; 2) Surveillance by FHRM 3X daily and weekly echo; 3) Treatment of 2° AVB identified by FHRM confirmed by echo. FHRM supported by echo will be leveraged to affirm the efficacy of rapid treatment of 2° AVB and incidence/outcome of AV interval prolongation as well as extra-nodal disease. By identifying 850 high-titer anti-Ro pregnancies in Step 1, FHRM in Step 2, and a single arm multicenter trial in Step 3, Aim 1 will determine whether expeditious treatment of 2° AVB restores NR. Mothers detecting an abnormal FHRM confirmed to be 2° AVB will be treated in ≤12 hours of detection with a potent dual anti-inflammatory approach, dexamethasone and IVIG, the primary outcome being percentage of treated fetuses whose rhythm regresses to NR. A sample size of 30 fetuses with 2° AVB ensures at least 80% power to detect an increase in the rate of reversal to NR from 25% (historical control rate) to 50% with treatment. Women with low-titer anti-Ro will not enter the Step 2-FHRM phase, but birth ECGs will be collected. Aim 2 assesses the incidence and natural history of a fetal prolonged AV interval ≤170 milliseconds (ms). Treatment of AV intervals >170ms will also be evaluated. Aim 3 assesses the incidence and outcome of fetuses with isolated extra-nodal cardiac disease. Impact: Strong preliminary data, interdisciplinary collaboration and national expertise support our application of the NICHD “Consortium Model” Network in providing a unique opportunity to reverse inflammatory/fibrotic sequelae of anti-Ro thereby preventing lifelong disability. It is anticipated that this study will decrease 3° AVB, yield evidence-based management guidelines, set precedent for universal pre-natal screening for anti-Ro, reduce costlier echo surveillance, and empower mothers in their own health care.

摘要