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Congenital heart disease linked to maternal autoimmunity against cardiac myosin.

ABSTRACT: Structural congenital heart disease (CHD) has not previously been linked to autoimmunity. In our study, we developed an autoimmune model of structural CHD that resembles hypoplastic left heart syndrome (HLHS), a life-threatening CHD primarily affecting the left ventricle. Because cardiac myosin (CM) is a dominant autoantigen in autoimmune heart disease, we hypothesized that immunization with CM might lead to transplacental passage of maternal autoantibodies and a prenatal HLHS phenotype in exposed fetuses. Elevated anti-CM autoantibodies in maternal and fetal sera, as well as IgG reactivity in fetal myocardium, were correlated with structural CHD that included diminished left ventricular cavity dimensions in the affected progeny. Further, fetuses that developed a marked HLHS phenotype had elevated serum titers of anti-?-adrenergic receptor Abs, as well as increased protein kinase A activity, suggesting a potential mechanism for the observed pathological changes. Our maternal-fetal model presents a new concept linking autoimmunity against CM and cardiomyocyte proliferation with cardinal features of HLHS. To our knowledge, this report shows the first evidence in support of a novel immune-mediated mechanism for pathogenesis of structural CHD that may have implications in its future diagnosis and treatment.

SUBMITTER: Cole CR

PROVIDER: S-EPMC4130707 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Congenital heart disease linked to maternal autoimmunity against cardiac myosin.

Cole Charles R CR Yutzey Katherine E KE Brar Anoop K AK Goessling Lisa S LS Van Vickle-Chavez Sarah J SJ Cunningham Madeleine W MW Eghtesady Pirooz P

Journal of immunology (Baltimore, Md. : 1950) 20140326 9

Structural congenital heart disease (CHD) has not previously been linked to autoimmunity. In our study, we developed an autoimmune model of structural CHD that resembles hypoplastic left heart syndrome (HLHS), a life-threatening CHD primarily affecting the left ventricle. Because cardiac myosin (CM) is a dominant autoantigen in autoimmune heart disease, we hypothesized that immunization with CM might lead to transplacental passage of maternal autoantibodies and a prenatal HLHS phenotype in expos ...[more]

PMID: 24670798

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Project description:PurposeTo characterize temporal trends and outcomes of delivery hospitalization with maternal congenital heart disease (CHD).Materials and methodsFor this repeated cross-sectional analysis, deliveries to women aged 15-54 years with maternal CHD were identified in the 2000-2018 National Inpatient Sample. Temporal trends in maternal CHD were analyzed using joinpoint regression to estimate the average annual percentage change (AAPC) with 95% CIs. The relationship between maternal CHD and several adverse maternal outcomes was analyzed with log-linear regression models. Risk for adverse outcomes in the setting of maternal CHD was further characterized based on additional diagnoses of cardiac comorbidity including congestive heart failure, arrhythmia, valvular disease, pulmonary disorders, and history of thromboembolism.ResultsOf 73,109,790 delivery hospitalizations, 51,841 had a diagnosis of maternal CHD (7.1 per 10,000). Maternal CHD rose from 4.2 to 10.9 per 10,000 deliveries (AAPC 4.8%, 95% CI 4.2%, 5.4%). Maternal CHD deliveries with a cardiac comorbidity diagnosis also increased from 0.6 to 2.6 per 10,000 from 2000 to 2018 (AAPC 8.4%, 95% CI 6.3%, 10.6%). Maternal CHD was associated with severe maternal morbidity (adjusted risk ratios [aRR] 4.97, 95% CI 4.75, 5.20), cardiac severe maternal morbidity (aRR 7.65, 95% CI 7.14, 8.19), placental abruption (aRR 1.30, 95% 1.21, 1.38), preterm delivery (aRR 1.47, 95% CI 1.43, 1.51), and transfusion (aRR 2.28, 95% CI 2.14, 2.42). Risk for severe morbidity (AAPC 4.7%, 95% CI 2.5%, 6.9%) and cardiac severe morbidity (AAPC 4.7%, 95% CI 2.5%, 6.9%) increased significantly among women with maternal CHD over the study period. The presence of cardiac comorbidity diagnoses was associated with further increased risk.ConclusionMaternal CHD is becoming more common among US deliveries. Among deliveries with maternal CHD, risk for severe morbidity is increasing. These findings support that an increasing burden of risk from maternal CHD in the obstetric population.

Project description:Background and objectiveAs more children with congenital heart disease survive to adulthood, adult congenital heart disease (ACHD) prevalence will increase (currently ~1 million US patients). Heart failure (HF) accounts for 26-42% of ACHD deaths. The rate of ACHD heart transplantations (ACHD HTx) is also increasing. We describe the ACHD HTx recipient/candidate cohort, analyze ACHD HTx outcomes, identify ACHD HTx specific challenges, and discuss opportunities to better serve more patients with ACHD HF.MethodsPubMed literature search including articles published from 2010-2023. Reviewed 89 studies, 67 included. Our search focused on the challenges of ACHD HTx and potential solutions.Key content and findingsACHD HTx recipients are young [median age 35 years, interquartile range (IQR): 24-46 years]. 87-95% of ACHD HTx recipients had prior cardiac surgery. The most common underlying diagnoses include transposition of the great arteries (31%) and Fontan/Glenn circulation (28%). 63% of listed ACHD HTx candidates received a transplant within one year of listing. Post-transplant 1-year survival is 80%, 5-year survival 74%, and 10-year survival 59%. There are 4 unique ACHD HTx challenges: (I) difficulty in assessing pulmonary hypertension, resulting in some centers selecting oversized donor hearts. However, selecting oversized hearts does not improve post-operative mortality and could prolong waitlist time. (II) Increased immunologic sensitization, increasing rejection risk. Desensitization therapy has enabled sensitized HTx recipients to enjoy outcomes similar to non-sensitized recipients. (III) Procedural complexity with ~30% of cases requiring additional surgical reconstruction. Detailed multidisciplinary planning, extensive imaging, and transferring the patient into the operating room early can help manage the complexities and reduce organ ischemic time. (IV) Increased intraoperative bleeding due to patients' surgical histories and circulatory collaterals. Preoperative collateral coil embolization and select utilization of hypothermic circulatory arrest can help reduce bleeding. Additional Fontan specific challenges include extensive great artery repair, liver failure, plastic bronchitis, and protein loss enteropathy. Finally, given limited donor heart availability, mechanical circulatory support is a promising technology for patients with ACHD HF.ConclusionsThe prevalence of ACHD HTx is slowly but steadily increasing. The operational complexity of ACHD HTx can be managed, and the majority of recipients have excellent outcomes (59% 10-year survival).

Project description:ImportanceWith the help of medical advances, more women with adult congenital heart disease (ACHD) are becoming pregnant. Adverse maternal, obstetric, and neonatal events occur more frequently in women with ACHD than in the general obstetric population. Adult congenital heart disease is heterogeneous, yet few studies have assessed whether maternal and neonatal outcomes differ across ACHD subtypes.ObjectiveTo assess the association of ACHD and its subtypes with pregnancy, maternal, and neonatal outcomes.Design, setting, and participantsThis cross-sectional study used data from the Discharge Abstract Database, which contains information on all hospitalizations in Canada (except Quebec) from fiscal years 2001-2002 through 2014-2015. Discharge Abstract Database information was linked with maternal and infant hospital records across Canada. All women who gave birth in hospitals during the study period were included in the study. Data were analyzed from December 18, 2017, to March 22, 2019.ExposuresWomen with ACHD were identified using diagnostic and procedural codes. Subtypes of ACHD were classified using the Anatomic and Clinical Classification of Congenital Heart Defects scheme.Main outcomes and measuresPrimary outcomes were defined a priori and included severe maternal morbidity (measured using the Maternal Morbidity Outcomes Indicator), neonatal morbidity and mortality (measured using the Neonatal Adverse Outcomes Indicator), ischemic placental disease, preterm birth, congenital anomalies, and small-for-gestational-age births. Absolute and relative rates of each outcome were calculated overall and by ACHD subtype. Logistic regression using generalized estimating equations assessed crude and adjusted odds ratios (aORs) for each outcome in women with ACHD compared with women without ACHD after adjustment for comorbidities, mode of delivery, and study year.ResultsThe 2114 women with ACHD included in the analysis (mean [SD] age, 29.4 [5.7] years) had significantly higher odds of maternal morbidity (aOR, 2.7; 95% CI, 2.2-3.4) and neonatal morbidity and mortality (aOR, 1.8; 95% CI, 1.6-2.1) compared with women without ACHD (n = 2 682 451). Substantial variation was observed between women with different subtypes of ACHD. For example, the aORs of preterm birth (<37 weeks) varied from 0.4 (95% CI, 0.4-0.5) for women with anomalies of atrioventricular junctions and valves to 4.7 (95% CI, 2.9-7.5) for women with complex anomalies of atrioventricular connections.Conclusions and relevanceThese results suggest that women with different subtypes of ACHD are not uniformly at risk for adverse maternal and neonatal outcomes. Although some women with ACHD can potentially expect healthy pregnancies, it appears that clinical care should be modified to address the heightened risks of certain ACHD subtypes.

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Congenital heart disease linked to maternal autoimmunity against cardiac myosin.

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Congenital heart disease linked to maternal autoimmunity against cardiac myosin.

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