Slow Heart Registry of Fetal Immune-mediated High Degree Heart Block

Study Overview
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Brief Summary
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Few studies are specifically designed to address health concerns that are already relevant during pregnancy. The consequence is a lack of evidence on best clinical practice. This includes mothers and their babies when pregnancy is complicated by an abnormally slow heart rate due to maternal antibody-mediated heart disease in the unborn baby (fetus). Since the late seventies, it has been possible to detect and monitor fetal disease by ultrasound images and to treat selected conditions with pharmaceuticals administered via the mother. To this day, physicians need to make decisions about the management of such pregnancies without evidence from prospective clinical trials on drug efficacy and safety. The SLOW HEART REGISTRY is a multi-centered prospective observational study that will address the knowledge gap to guide future management of high-degree immune-mediated heart block to the best of care. The study seeks to establish an international database of the management and outcome of affected fetuses, to be used to publish information on the results of currently available prenatal care and to evaluate the need for additional research.

Detailed Description
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The SLOW HEART REGISTRY is a multi-centered prospective observational study of fetuses diagnosed with high-degree immune-mediated atrio-ventricular heart block (AVB). The study seeks to establish an international database of the management and outcome of affected fetuses, to be used to publish information on the results of currently available prenatal care and to evaluate the need for additional research. The study aims are to document the outcome of patients diagnosed prenatally with immune-mediated 2nd or 3rd degree AVB irrespective of the primary choice of prenatal care. The primary objective will be to determine the rate of transplant-free survival to 1 year of life of fetuses with AVB based on the prenatal management decision: Cohort 1: Fetuses not treated with fluorinated glucocorticoids Cohort 2: Fetuses treated with fluorinated glucocorticoids from the time of immune-mediated AVB diagnosis. Secondary objectives will be to determine: the evolution of clinical findings from AVB diagnosis to birth (AV conduction; fetal heart rate; other NL manifestations; fetal growth; effusions/hydrops) between cohorts; the need of new/additional treatment (steroids; beta-mimetics; IVIG) to birth; gestational age and weight at birth; postnatal management (pacing; steroids; IVIG); and clinical evolution from birth to 1-3 years of life (cardiac function; developmental milestones; infant growth; health). Prevalence of relevant fetal-maternal events and complications (death; IUGR; morbidity) between the study cohorts will also be determined. All management is decided by the treating center and physicians in accordance to institutional guidelines and clinical findings. Patient enrollment in the SLOW HEART REGISTRY is possible within up to 8 days of the initial management decision. Participation in this prospective observational cohort study requires site REB approval and an executed legal contract with the primary investigator/SickKids Hospital, Toronto.

Official Title
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Slow Heart Registry: A Prospective Observational Cohort Study of Fetal Immune-mediated High Degree Heart Block

Conditions
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Heart Block Complete, Heart Block Second Degree

Intervention / Treatment
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* Drug: Dexamethasone
* Other: No Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed maternal consent to participate in the Slow Heart Registry High-degree (2nd; 2:1; 2nd-3rd or 3rd degree) AVB diagnosed ≤ 32+0 weeks with or without hydrops Enrollment within maximally 8 days of high-degree AVB diagnosis Positive or pending anti-Ro/La antibody test results at the time of enrollment Exclusion Criteria: AVB associated with major CHD (e.g. left atrial isomerism, cc-TGA) AVB with known negative anti-Ro and/or La antibody test result at enrollment 1st degree AVB Sinus bradycardia with normal 1:1 AV conduction Blocked atrial bigeminy (irregular atrial rate with failure of AV conduction of the premature atrial beat) Primary delivery for postnatal treatment Maternal-fetal conditions (other than cardiac NL) associated with high odds of premature delivery or death (e.g. renal failure, significant infectious diseases, major extracardiac anomalies, PROM, etc.) Preexisting maternal mental disorder (e.g. bipolar, mania, severe depression, substance abuse) Poorly controlled insulin-dependent diabetes (HbA1c >7%) at CAVB diagnosis Oligohydramnios (deepest/maximal vertical pocket <2 cm) Severe IUGR (estimated fetal weight <3rd percentile)

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Prospective observational cohort 1<br>Complete AVB (3rd degree) diagnosed ≤ 32+0 weeks with or without hydrops | Drug: Dexamethasone<br>* All management decisions are made by the primary physician and may include: 1) no treatment with dexamethasone or 2) treatment with dexamethasone from the time of enrollment<br>Other: No Dexamethasone<br>* All management decisions are made by the primary physician and may include: 1) no treatment with dexamethasone or 2) treatment with dexamethasone from the time of enrollment<br>|
| Prospective observational cohort 2<br>Incomplete AVB (2nd; 2:1; 2nd-3rd degree) diagnosed ≤ 32+0 weeks with or without hydrops | Drug: Dexamethasone<br>* All management decisions are made by the primary physician and may include: 1) no treatment with dexamethasone or 2) treatment with dexamethasone from the time of enrollment<br>Other: No Dexamethasone<br>* All management decisions are made by the primary physician and may include: 1) no treatment with dexamethasone or 2) treatment with dexamethasone from the time of enrollment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from cardiac death ≥1 year of life |  | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with fetal and neonatal death and their causes/factors |  | 1 month | 
| Proportion of participants with change in prenatal treatment |  | up to 6 months | 
| Proportion of secondarily treated patients (initially untreated group 1 cases) |  | up to 6 months | 
| Proportion of serious pregnancy outcomes (IUFD, IUGR <3rd percentile, delivery <35 weeks) |  | up to 6 months | 
| Proportion of patients/group with progression from incomplete to complete AVB by 1 year |  | Fetal diagnosis to 12 months | 
| Proportion of maternal serious adverse events and outcomes |  | Fetal diagnosis to 12 months | 
| Average gestational age at birth |  | Birth | 
| Average birth weight |  | Birth | 
| Freedom from permanent pacemaker implantation from birth to 1 year of life |  | Birth to 12 months | 
| Prevalence of significant heart failure (HF score, echo, HF treatment) at 1 year of life |  | 12 months | 
| Proportion of children with moderate/severe neuro-developmental delay at 12-18 months |  | 12-18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fetal, heart block, anti-Ro antibodies, steroids, outcome