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Peter M Izmirly - One of the best experts on this subject based on the ideXlab platform.
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hydroxychloroquine to prevent recurrent congenital heart block in fetuses of anti ssa ro positive mothers
Journal of the American College of Cardiology, 2020Co-Authors: Peter M Izmirly, Bettina F Cuneo, Deborah M Friedman, Robert R Clancy, Rebecca E Cohen, Joshua A Copel, N Costedoatchalumeau, Mimi Y Kim, Colin K L Phoon, Kimberly RobinsAbstract:Abstract Background Experimental and clinical evidence support the role of macrophage Toll-like receptor signaling in maternal anti-SSA/Ro–mediated congenital heart block (CHB). Objectives Hydroxychloroquine (HCQ), an orally administered Toll-like receptor antagonist widely used in lupus including during pregnancy, was evaluated for efficacy in reducing the historical 18% recurrence rate of CHB. Methods This multicenter, open-label, single-arm, 2-stage clinical trial was designed using Simon’s optimal approach. Anti-SSA/Ro–positive mothers with a previous pregnancy complicated by CHB were recruited (n = 19 Stage 1; n = 35 Stage 2). Patients received 400 mg daily of HCQ prior to completion of gestational week 10, which was maintained through pregnancy. The primary outcome was 2° or 3° CHB any time during pregnancy, and secondary outcomes included isolated Endocardial Fibroelastosis, 1° CHB at birth and skin rash. Results By intention-to-treat (ITT) analysis, 4 of 54 evaluable pregnancies resulted in a primary outcome (7.4%; 90% confidence interval: 3.4% to 15.9%). Because 9 mothers took potentially confounding medications (fluorinated glucocorticoids and/or intravenous immunoglobulin) after enrollment but prior to a primary outcome, to evaluate HCQ alone, 9 additional mothers were recruited and followed the identical protocol. In the per-protocol analysis restricted to pregnancies exposed to HCQ alone, 4 of 54 (7.4%) fetuses developed a primary outcome as in the ITT. Secondary outcomes included mild Endocardial Fibroelastosis (n = 1) and cutaneous neonatal lupus (n = 4). Conclusions These prospective data support that HCQ significantly reduces the recurrence of CHB below the historical rate by >50%, suggesting that this drug should be prescribed for secondary prevention of fetal cardiac disease in anti-SSA/Ro-exposed pregnancies. (Preventive Approach to Congenital Heart Block With Hydroxychloroquine [PATCH]; NCT01379573 )
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autoimmune mediated congenital heart block
Best Practice & Research in Clinical Obstetrics & Gynaecology, 2020Co-Authors: Benjamin J Wainwright, Amit Saxena, Rohit Bhan, Catherine Trad, Rebecca E Cohen, Peter M IzmirlyAbstract:Abstract Autoimmune-mediated congenital heart block (CHB) is a severe manifestation of neonatal lupus in which conduction tissues of the fetal heart are damaged. This occurs due to passive transference of maternal anti-SSA/Ro and anti-SSB/La autoantibodies and subsequent inflammation and fibrosis of the atrioventricular (AV) node. Notably, the disease manifests after the fetal heart has structurally developed, ruling out other anatomical abnormalities that could otherwise contribute to the block of conduction. Complete AV block is irreversible and the most common manifestation of CHB, although other cardiac complications such as Endocardial Fibroelastosis (EFE), dilated cardiomyopathy, and valvular insufficiency have been observed. In this review, we detail the classification, prevalence, pathogenesis, and clinical management recommendations for autoimmune CHB.
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autoimmune congenital heart block complex and unusual situations
Lupus, 2016Co-Authors: Pilar Britozeron, Peter M Izmirly, Manuel Ramoscasals, Munther A KhamashtaAbstract:Autoimmune congenital heart block (ACHB) is an immune-mediated cardiac disease included among the manifestations collectively referred to as neonatal lupus. The placental transference of maternal Ro/La autoantibodies may damage the conduction tissues during fetal development leading to blocking of signal conduction at the atrioventricular (AV) node in an otherwise structurally normal heart. Irreversible complete AV block is the main cardiac manifestation of ACHB, but some babies may develop Endocardial Fibroelastosis, valvular insufficiency, and/or frank cardiomyopathies with significantly reduced cardiac function requiring transplant. The severity of ACHB is illustrated by a global mortality rate of 20% and pacemaker rates of at least 64%, often within the first year of life. This review analyses the main complex and/or unusual clinical situations associated with ACHB, including unusual maternal immunological profiles, infrequent maternal autoimmune diseases, cardiac damage unrelated to AV block, fetal invasive management, late complications after birth, risk of congenital heart block (CHB) in ovodonation and in vitro fertilization techniques, the role of maternal features other than autoimmunity, the influence of the birth order or the risk of CHB in twins and triplets.
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maternal and fetal factors associated with mortality and morbidity in a multi racial ethnic registry of anti ssa ro associated cardiac neonatal lupus
Circulation, 2011Co-Authors: Peter M Izmirly, Amit Saxena, Deborah M Friedman, Dan Wang, Sara Sahl, Carolina Llanos, Jill P BuyonAbstract:Background—Cardiac manifestations of neonatal lupus include conduction disease and, rarely, an isolated cardiomyopathy. This study was initiated to determine the mortality and morbidity of cardiac neonatal lupus and associated risk factors in a multi–racial/ethnic US-based registry to provide insights into the pathogenesis of antibody-mediated injury and data for counseling. Methods and Results—Three hundred twenty-five offspring exposed to maternal anti-SSA/Ro antibodies with cardiac neonatal lupus met entry criteria. Maternal, fetal echocardiographic, and neonatal risk factors were assessed for association with mortality. Fifty-seven (17.5%) died, 30% in utero. The probability of in utero death was 6%. The cumulative probability of survival at 10 years for a child born alive was 86%. Fetal echocardiographic risk factors associated with increased mortality in a multivariable analysis of all cases included hydrops and Endocardial Fibroelastosis. Significant predictors of in utero death were hydrops and ea...
N Costedoatchalumeau - One of the best experts on this subject based on the ideXlab platform.
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hydroxychloroquine to prevent recurrent congenital heart block in fetuses of anti ssa ro positive mothers
Journal of the American College of Cardiology, 2020Co-Authors: Peter M Izmirly, Bettina F Cuneo, Deborah M Friedman, Robert R Clancy, Rebecca E Cohen, Joshua A Copel, N Costedoatchalumeau, Mimi Y Kim, Colin K L Phoon, Kimberly RobinsAbstract:Abstract Background Experimental and clinical evidence support the role of macrophage Toll-like receptor signaling in maternal anti-SSA/Ro–mediated congenital heart block (CHB). Objectives Hydroxychloroquine (HCQ), an orally administered Toll-like receptor antagonist widely used in lupus including during pregnancy, was evaluated for efficacy in reducing the historical 18% recurrence rate of CHB. Methods This multicenter, open-label, single-arm, 2-stage clinical trial was designed using Simon’s optimal approach. Anti-SSA/Ro–positive mothers with a previous pregnancy complicated by CHB were recruited (n = 19 Stage 1; n = 35 Stage 2). Patients received 400 mg daily of HCQ prior to completion of gestational week 10, which was maintained through pregnancy. The primary outcome was 2° or 3° CHB any time during pregnancy, and secondary outcomes included isolated Endocardial Fibroelastosis, 1° CHB at birth and skin rash. Results By intention-to-treat (ITT) analysis, 4 of 54 evaluable pregnancies resulted in a primary outcome (7.4%; 90% confidence interval: 3.4% to 15.9%). Because 9 mothers took potentially confounding medications (fluorinated glucocorticoids and/or intravenous immunoglobulin) after enrollment but prior to a primary outcome, to evaluate HCQ alone, 9 additional mothers were recruited and followed the identical protocol. In the per-protocol analysis restricted to pregnancies exposed to HCQ alone, 4 of 54 (7.4%) fetuses developed a primary outcome as in the ITT. Secondary outcomes included mild Endocardial Fibroelastosis (n = 1) and cutaneous neonatal lupus (n = 4). Conclusions These prospective data support that HCQ significantly reduces the recurrence of CHB below the historical rate by >50%, suggesting that this drug should be prescribed for secondary prevention of fetal cardiac disease in anti-SSA/Ro-exposed pregnancies. (Preventive Approach to Congenital Heart Block With Hydroxychloroquine [PATCH]; NCT01379573 )
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anti ssa ro and anti ssb la antibody mediated congenital heart block
Lupus, 2005Co-Authors: N Costedoatchalumeau, Sophie Georginlavialle, Z Amoura, J C PietteAbstract:When anti-SSA/Ro antibodies are present in sera of mothers with connective tissue diseases, the incidence of congenital heart block (CHB) has been reported to be 1-2% in live births. The risk of recurrence of CHB in a subsequent child remains limited to 10-16%. CHBs are usually complete but CHB of the first or second degree can also be observed. In some cases, CHB is associated with Endocardial Fibroelastosis. Late-onset cardiomyopathy may occur later in life in these children. The mortality of CHB, which is predominant in utero and in the first months of life, is an estimated 16-19%. A pacemaker is required in about 66% of cases. Curative treatment of CHB is based on fluorinated steroids (dexamethasone or betamethasone) that do cross the placenta in an active form. Guidelines are available but further studies are needed to optimize treatment.
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anti ssa ro antibodies and the heart more than complete congenital heart block a review of electrocardiographic and myocardial abnormalities and of treatment options
Arthritis Research & Therapy, 2005Co-Authors: N Costedoatchalumeau, Z Amoura, Elisabeth Villain, Laurence Cohen, Jeancharles PietteAbstract:Apart from complete and incomplete congenital heart block (CHB), new cardiac manifestations related to anti-SSA/Ro antibodies have been reported in children born to mothers bearing these antibodies. These manifestations include transient fetal first-degree heart block, prolongation of corrected QT (QTc) interval, sinus bradycardia, late-onset cardiomyopathy, Endocardial Fibroelastosis and cardiac malformations. Anti-SSA/Ro antibodies are not considered pathogenic to the adult heart, but a prolongation of the QTc interval has recently been reported in adult patients and is still a matter of debate. Treatment of CHB is not well established and needs to be assessed carefully. The risks and benefits of prenatal fluorinated steroids are discussed.
Sitaram M Emani - One of the best experts on this subject based on the ideXlab platform.
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postnatal left ventricular diastolic function after fetal aortic valvuloplasty
American Journal of Cardiology, 2011Co-Authors: Sitaram M Emani, Kevin G Friedman, Renee Margossian, Dionne A Graham, David M HarrildAbstract:Fetal aortic balloon valvuloplasty (FAV) has shown promise in altering in utero progression of aortic stenosis to hypoplastic left heart syndrome. In patients who achieve a biventricular circulation after FAV, left ventricular (LV) compliance may be impaired. Echocardiographic indexes of diastolic function were compared between patients with biventricular circulation after FAV, congenital aortic stenosis (AS), and age-matched controls. In the neonatal period, patients with FAV had similar LV, aortic, and mitral valve dimensions but more evidence of Endocardial Fibroelastosis than patients with AS. Patients with FAV underwent more postnatal cardiac interventions than patients with AS (p = 0.007). Mitral annular early diastolic tissue velocity (E′) was lower in patients with FAV and those with AS and controls in the neonatal period and over follow-up (p
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primary left ventricular rehabilitation is effective in maintaining two ventricle physiology in the borderline left heart
The Journal of Thoracic and Cardiovascular Surgery, 2009Co-Authors: Sitaram M Emani, Wayne Tworetzky, Doff B Mcelhinney, Emile A Bacha, Gerald R Marx, Frank A Pigula, Pedro J Del NidoAbstract:Objective Borderline left heart disease is characterized by left heart obstructive lesions (coarctation, aortic and mitral stenoses, left ventricular hypoplasia) and Endocardial Fibroelastosis. The multilevel obstruction and impaired left ventricular systolic and diastolic function contribute to failure of biventricular circulation. We studied the effects of left ventricular rehabilitation—Endocardial Fibroelastosis resection with mitral or aortic valvuloplasty—on left ventricular function and clinical outcomes. Methods All patients with borderline left heart structures and Endocardial Fibroelastosis who underwent a primary left ventricular rehabilitation procedure were retrospectively analyzed to determine operative mortality, reintervention rates, and hemodynamic status. Left heart dimensions and hemodynamics were recorded from preoperative and postoperative echocardiogram and cardiac catheterization. Postoperative left atrial pressure was obtained from the intracardiac line early after left ventricular rehabilitation. Preoperative and postoperative values were compared by paired t test. Results Between 1999 and 2008, 9 patients with Endocardial Fibroelastosis and borderline left heart disease underwent left ventricular rehabilitation at a median age of 5.6 months (range, 1–38 months). There was no operative mortality, and at a median follow-up of 25 months (6 months to 10 years) there was 1 death from noncardiac causes and 2 patients required reoperations. Significant increases in ejection fraction and left ventricular end-diastolic volume were observed, whereas left atrial pressure and right ventricular/left ventricular pressure ratios decreased postoperatively. Conclusion In patients with borderline left hearts, primary left ventricular rehabilitation with Endocardial Fibroelastosis resection and mitral and aortic valvuloplasty results in improved left ventricular systolic and diastolic performance and decreased right ventricular pressures. This approach may provide an alternative to single-ventricle management in this difficult patient group.
Pedro J Del Nido - One of the best experts on this subject based on the ideXlab platform.
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distention of the immature left ventricle triggers development of Endocardial Fibroelastosis an animal model of Endocardial Fibroelastosis introducing morphopathological features of evolving fetal hypoplastic left heart syndrome
BioMed Research International, 2015Co-Authors: Shogo Shimada, Pedro J Del Nido, Christian Robles, Ben Minwoo Illigens, Alejandra Casar M Berazaluce, Ingeborg FriehsAbstract:Background. Endocardial Fibroelastosis (EFE), characterized by a diffuse Endocardial thickening through collagen and elastin fibers, develops in the human fetal heart restricting growth of the left ventricle (LV). Recent advances in fetal imaging indicate that EFE development is directly associated with a distended, poorly contractile LV in evolving hypoplastic left heart syndrome (HLHS). In this study, we developed an animal model of EFE by introducing this human fetal LV morphopathology to an immature rat heart. Methods and Results. A neonatal donor heart, in which aortic regurgitation (AR) was created, was heterotopically transplanted into a recipient adult rat. AR successfully induced the LV morphology of evolving HLHS in the transplanted donor hearts, which resulted in the development of significant EFE covering the entire LV cavity within two weeks postoperatively. In contrast, posttransplants with a competent aortic valve displayed unloaded LVs with a trace of EFE. Conclusions. We could show that distention of the immature LV in combination with stagnant flow triggers EFE development in this animal model. This model would serve as a robust tool to develop therapeutic strategies to treat EFE while providing insight into its pathogenesis.
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left ventricular diastolic heart failure in teenagers who underwent balloon aortic valvuloplasty in early infancy
American Journal of Cardiology, 2010Co-Authors: James E. Lock, Pedro J Del Nido, Joshua D Robinson, Robert L Geggel, Antonio R PerezataydeAbstract:We report 4 teenage patients who, after successful palliation of severe aortic valve stenosis by balloon aortic valvuloplasty in early infancy, presented within the previous 3 years with significant left ventricular (LV) diastolic heart failure. All patients had remained asymptomatic until their teenage years and had normal or hyperdynamic LV systolic function on presentation, with limited residual aortic valve stenosis and regurgitation. All underwent echocardiography, cardiac catheterization, and cardiac magnetic resonance evaluation. One notable common feature in the 4 patients was the presence of a confluent layer of LV subEndocardial hyperenhancement demonstrated by late gadolinium enhancement technique. Histopathology was available for 2 patients, which documented significant LV Endocardial Fibroelastosis. One patient who underwent Endocardial Fibroelastosis resection in conjunction with aortic valve replacement had late clinical improvement. In conclusion, this group of patients may represent an important emerging clinical entity and merits close clinical surveillance, with prospective assessment of diastolic function.
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primary left ventricular rehabilitation is effective in maintaining two ventricle physiology in the borderline left heart
The Journal of Thoracic and Cardiovascular Surgery, 2009Co-Authors: Sitaram M Emani, Wayne Tworetzky, Doff B Mcelhinney, Emile A Bacha, Gerald R Marx, Frank A Pigula, Pedro J Del NidoAbstract:Objective Borderline left heart disease is characterized by left heart obstructive lesions (coarctation, aortic and mitral stenoses, left ventricular hypoplasia) and Endocardial Fibroelastosis. The multilevel obstruction and impaired left ventricular systolic and diastolic function contribute to failure of biventricular circulation. We studied the effects of left ventricular rehabilitation—Endocardial Fibroelastosis resection with mitral or aortic valvuloplasty—on left ventricular function and clinical outcomes. Methods All patients with borderline left heart structures and Endocardial Fibroelastosis who underwent a primary left ventricular rehabilitation procedure were retrospectively analyzed to determine operative mortality, reintervention rates, and hemodynamic status. Left heart dimensions and hemodynamics were recorded from preoperative and postoperative echocardiogram and cardiac catheterization. Postoperative left atrial pressure was obtained from the intracardiac line early after left ventricular rehabilitation. Preoperative and postoperative values were compared by paired t test. Results Between 1999 and 2008, 9 patients with Endocardial Fibroelastosis and borderline left heart disease underwent left ventricular rehabilitation at a median age of 5.6 months (range, 1–38 months). There was no operative mortality, and at a median follow-up of 25 months (6 months to 10 years) there was 1 death from noncardiac causes and 2 patients required reoperations. Significant increases in ejection fraction and left ventricular end-diastolic volume were observed, whereas left atrial pressure and right ventricular/left ventricular pressure ratios decreased postoperatively. Conclusion In patients with borderline left hearts, primary left ventricular rehabilitation with Endocardial Fibroelastosis resection and mitral and aortic valvuloplasty results in improved left ventricular systolic and diastolic performance and decreased right ventricular pressures. This approach may provide an alternative to single-ventricle management in this difficult patient group.
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usefulness of magnetic resonance imaging of left ventricular Endocardial Fibroelastosis in infants after fetal intervention for aortic valve stenosis
American Journal of Cardiology, 2005Co-Authors: Wayne Tworetzky, Audrey C. Marshall, James E. Lock, Pedro J Del Nido, Andrew J Powell, Tal GevaAbstract:This report describes the use of myocardial delayed-enhancement magnetic resonance imaging to delineate the extent of Endocardial Fibroelastosis (EFE) in 4 infants after fetal balloon aortic valvuloplasty. The preoperative mapping of EFE followed by extensive resection led to biventricular physiology in 2 patients.
Jeancharles Piette - One of the best experts on this subject based on the ideXlab platform.
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anti ssa ro antibodies and the heart more than complete congenital heart block a review of electrocardiographic and myocardial abnormalities and of treatment options
Arthritis Research & Therapy, 2005Co-Authors: N Costedoatchalumeau, Z Amoura, Elisabeth Villain, Laurence Cohen, Jeancharles PietteAbstract:Apart from complete and incomplete congenital heart block (CHB), new cardiac manifestations related to anti-SSA/Ro antibodies have been reported in children born to mothers bearing these antibodies. These manifestations include transient fetal first-degree heart block, prolongation of corrected QT (QTc) interval, sinus bradycardia, late-onset cardiomyopathy, Endocardial Fibroelastosis and cardiac malformations. Anti-SSA/Ro antibodies are not considered pathogenic to the adult heart, but a prolongation of the QTc interval has recently been reported in adult patients and is still a matter of debate. Treatment of CHB is not well established and needs to be assessed carefully. The risks and benefits of prenatal fluorinated steroids are discussed.
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Anti-SSA/Ro antibodies and the heart: more than complete congenital heart block? A review of electrocardiographic and myocardial abnormalities and of treatment options.
Arthritis research & therapy, 2005Co-Authors: Nathalie Costedoat-chalumeau, Z Amoura, Elisabeth Villain, Laurence Cohen, Jeancharles PietteAbstract:Apart from complete and incomplete congenital heart block (CHB), new cardiac manifestations related to anti-SSA/Ro antibodies have been reported in children born to mothers bearing these antibodies. These manifestations include transient fetal first-degree heart block, prolongation of corrected QT (QTc) interval, sinus bradycardia, late-onset cardiomyopathy, Endocardial Fibroelastosis and cardiac malformations. Anti-SSA/Ro antibodies are not considered pathogenic to the adult heart, but a prolongation of the QTc interval has recently been reported in adult patients and is still a matter of debate. Treatment of CHB is not well established and needs to be assessed carefully. The risks and benefits of prenatal fluorinated steroids are discussed.