Dr. Jill Buyon, MD- Preventive Approach to Congenital Heart Block With Hydroxychloroquine (PATCH) @JillBuyonMD @NYUL...

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Dr. Jill Buyon, MD is a Rheumatology Specialist with over 44 years of expertise in the medical industry in New York, NY. In 1978, she received her medical degree from Yeshiva University's College of Medicine. NYU Langone Health Tisch Hospital and NYU Langone Health Tisch Hospital are also linked with her. In this video Dr. Buyon discusses Preventive Approach to Congenital Heart Block With Hydroxychloroquine (PATCH).


Brief Synopsis:
Whether they have very active lupus, are in remission, or have just vague symptoms, women with antibodies to proteins called SSA/Ro and SSB/La have a 2% chance of conceiving a kid with a life-threatening cardiac disease. This heart condition is known as congenital heart block (the most dangerous of which is third degree total block), and it is hypothesized to be caused by autoantibodies. The heart beats abnormally slowly, and almost all children under the age of 20 require permanent pacemakers. Women who have had one child with heart block are ten times more likely to have another child with the same heart issue. Unfortunately, even careful monitoring with sophisticated procedures during pregnancy cannot reverse total heart block once it has been detected. As a result, prevention-oriented interventions are essential. For the first time, researchers will see if hydroxychloroquine, a medicine used by many SLE patients, may prevent the development of this heart problem. Experiments in the lab suggest that this medication, which crosses the placenta, may reduce the inflammation caused by anti-Ro antibodies being passed to the fetus. If Stage 1 is successful, the trial will enroll 19 patients in Stage 1 and 35 patients in Stage 2 using a Simon's 2-Stage design. Patients may be taking hydroxychloroquine already or will begin as soon as pregnancy is established. It is hoped that in Stage 1, fewer than 3 cases of heart block would occur, and in Stage 2, fewer than 6 cases will occur out of 54 individuals. The findings of this study are expected to become an important element of the counseling of women who are considering pregnancy and have anti-Ro/La antibodies.
Description in detail:

The development of congenital heart block (CHB) in an offspring is one of the strongest clinical connections with autoantibodies directed against components of the Ro/La ribonucleoprotein complex, a scary prospect facing 2% of primigravid mothers with these reactivities. Women who have had a previous afflicted kid are at a 10-fold increased risk. Irreversible block and significant cardiac injury have been recorded within 7 days after a normal rhythm and PR interval, despite massive multicenter trials attempting to prevent disease through recurrent in utero monitoring. CHB is linked to a high rate of mortality and morbidity. Two recent prospective studies (20 women from the United States and 15 from Europe) using an identical IVIG replacement dose methodology showed that 1) this intervention did not prevent CHB recurrence. 2) The recurrence rate of 17-18% is quite high. 3) Patient recruiting is doable. Basic science investigating the pathophysiology of illness at the time of the IVIG trials supported the idea that Toll Like Receptor (TLR) signaling in response to ligation of ssRNA (hY3) complexed to the Ro protein contributes to fibrosis. This finding prompted researchers to conduct in vitro investigations on chloroquine's ability to block endosomal acidification, as well as a retrospective record review to assess the use of hydroxychloroquine (HCQ). The evidence suggests that HCQ is effective. As a result, the purpose of this research is to see if taking hydroxychloroquine during pregnancy prevents CHB in a high-risk population. The trial is open-label and uses Simon's 2-stage optimum design to allow for early termination if treatment efficacy is not achieved. The first stage necessitates the participation of 19 individuals. Despite the rarity of the disease and the requirement of a previous CHB kid, this idea is viable, according to the US Research Registry for Neonatal Lupus. The study is ended after the first stage if three or more moms have a kid with 2nd or 3rd degree CHB. If this does not happen, money will be sought to enlist another 35 moms in the second round, bringing the total number of subjects to 54. If fewer than 6 out of 54 moms have a kid with advanced CHB, treatment will be judged effective. If the true recurrence rate with therapy is 5%, the study has 90% power to infer that hydroxychloroquine is preventative using this design. Furthermore, if the genuine recurrence rate is 18 percent, the probability of rejecting the treatment for further research is 95 percent. The protocol will include serial echocardiograms (to monitor the PR interval) and blood draws (for IFNnsignatures and antibody titers). The findings of this study are expected to become an important element of the counseling of women who are considering pregnancy and have anti-SSA/Ro-SSB/La antibodies.