Geoepidemiology and clinical characteristics of neonatal lupus erythematosus: a systematic literature review of individual patients' data

Background/aim: Neonatal lupus erythematosus (NLE) is an autoimmune syndrome caused by transplacental transmission of maternal autoantibodies, often with devastating consequences. The objective of this systematic literature review was to analyze the demographic data, geoepidemiology, clinical, and serological characteristics associated with NLE. Materials and methods: We performed a systematic literature search of the Pubmed database covering the period from 1976 to August 2015, using the MeSH terms "neonatal lupus" or "congenital heart block". To be included in the study, articles of any type (original articles, case series, and case reports) had to report on infants with NLE on an individualized (i.e. patient-by-patient) basis. Results: A total of198 studies were included in the review, reporting on a total of 755 NLE patients. The most frequently reported clinical manifestations of NLE were congenital heart block (CHB, 65.2%), cutaneous lupus (33.1%), and cytopenias (15.5%). We found differences in NLE characteristics based on study geographical origin, with CHB being much more frequent in patients of European or American descent (49.4% and 35%, respectively), while reports originating from Asia reported a higher prevalence of skin involvement (45.2%). Most CHB cases (72.9%) were diagnosed between the 18th and 26th week of gestation. Conclusions: Phenotypic differences of NLE depending on race and country may reflect true pathophysiologic differences or methodologic discrepancies. While maternal autoimmune disease is not a prerequisite for the development of NLE, the existence of a truly "immunonegative" CHB is questionable.

Maternal and fetal factors associated with mortality and morbidity in a multi-racial/ethnic registry of anti-SSA/Ro-associated cardiac neonatal lupus.

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 earlier diagnosis, and of postnatal death were hydrops, endocardial fibroelastosis, and lower ventricular rate. Isolated heart block was associated with a 7.8% case fatality rate, whereas the concomitant presence of dilated cardiomyopathy or endocardial fibroelastosis quadrupled the case fatality rate. There was a significantly higher case fatality rate in minorities compared with whites, who were at a lower risk of hydrops and endocardial fibroelastosis. Pacing was required in 70%; cardiac transplantation was required in 4 children. CONCLUSION: Nearly one fifth of fetuses who develop cardiac neonatal lupus die of complications predicted by echocardiographic abnormalities consistent with antibody-associated disease beyond the atrioventricular node. The disparity in outcomes observed between minorities and whites warrants further investigation.

Atypical presentation of Takayasu aortitis and myocarditis contributing to sudden death in a young Canadian first nations adult.

This is a rare presentation of Takayasu arteritis in a 30-year-old Canadian First Nations woman with cardiac and aortic root-predominant disease, which manifested in complete heart block. She had a past medical history significant for substance misuse. At presentation, cardiac magnetic resonance imaging identified diffuse thickening of the left atrium and ventricular outflow tract with left ventricular cavity dilation and preserved systolic function. A pacemaker was inserted at this time. Nine months later, the patient died following an out-of-hospital cardiac arrest in the context of cocaine intoxication. At autopsy, the cardiac thickening was also found to involve the proximal aortic root, which on microscopy demonstrated non-infectious aortitis and myocarditis with a granulomatous inflammatory pattern and dense fibrosis indicative of Takayasu arteritis. Important clinical clues to the diagnosis include age, sex, and Pacific Islands, American indigenous and Asian ethnicity. The case also underscores the need to rule out secondary causes of complete heart block, including systemic vasculitides, for all patients regardless of substance use history.

Electrocardiographic Time to Intrinsicoid Deflection and Heart Failure: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Time to intrinsicoid deflection (ID), the time from onset of the QRS complex to the peak of the R wave on the electrocardiogram, represents delayed ventricular activation and suggests that impaired myocardial function is present. It is unknown whether delayed time to ID is predictive of future heart failure (HF) events. HYPOTHESIS: Delayed time to ID is predictive of future HF events. METHODS: A total of 6394 participants (mean age, 62 ± 10 years; 54% women; 38% whites, 28% blacks, 22% Hispanics, 12% Chinese Americans) without clinically apparent cardiovascular disease or major ventricular conduction delay (QRS ≥120 ms) from the Multi-Ethnic Study of Atherosclerosis were included. Time to ID was automatically measured from baseline electrocardiograms (2000-2002) as the maximum value in leads V5 and V6 . Cox regression was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between time to ID and HF. RESULTS: Over a median follow-up of 11.2 years, a total of 217 (3.4%) participants developed HF (incidence rate per 1000 person-years: 3.33, 95% CI: 2.91-3.80). In a multivariable Cox regression analysis adjusted for demographics, cardiovascular risk factors, and potential confounders, each 10-ms increase in maximum time to ID was associated with an increased risk for HF (HR: 1.42, 95% CI: 1.15-1.74). The results remained similar when stratified by age, sex, and race/ethnicity. CONCLUSIONS: Delayed time to ID is able to identify individuals at risk for developing HF before major ventricular conduction delays (eg, bundle branch block) are evident.

Effects of race and health insurance on the rates of pacemaker implantation for complete heart block in the United States.

Although indicated for adults with complete heart block, pacemaker implantation is not always practiced. There are gross discrepancies by race, type of health insurance coverage, and size of hospital of admission in the utilization of pacemakers.

Complete heart block in an Inuit family.

An Inuit family from Cape Dorset, Northwest Territories is described; six had documented complete heart block, one high grade atrioventricular block, one bi- or trifascicular block and all suffered syncope. One other member received a pacemaker for unknown reasons. Two of three middle-aged relatives had minor conduction abnormalities. All younger family members who were examined had no conduction problems. This suggests a heritable form of adult onset complete heart block, the largest series reported in the English literature.

Lower prevalence of intraventricular block in African-American patients compared with Caucasian patients: an electrocardiographic study II.

BACKGROUND: Electrocardiographic (ECG) differences occur between African-American and white persons. METHODS: Intraventricular conduction abnormalities of ECGs of 2,123 African-American and white hospital patients ages 20-99 years were studied in a consecutive manner. RESULTS: Intraventricular conduction abnormalities develop later in life and are less common in African-American patients, compared with white patients. The prevalence of conduction abnormalities increases with advancing age in both races. Left- and right ventricular conduction abnormalities begin to rise at age 50 for white patients but begin to rise at age 70 for African-American patients. The prevalence of left ventricular conduction abnormalities peaks in the ninth decade of life in both races but declines in both races in the tenth decade of life. The prevalence of right ventricular conduction abnormalities gradually increases and peaks in the tenth decade of life in both races. CONCLUSIONS: The prevalence of intraventricular block is significantly less in African-American patients, compared with white patients--occurring in 8.6% of African-American patients and in 15.2% of white patients. The prevalence of intraventricular block is lowest in African-American women at 6.5% and highest in white men at 16.8%.

Comparison of the prevalence of first-degree atrioventricular block in African-American and in Caucasian patients: an electrocardiographic study III.

BACKGROUND: Electrocardiographic (ECG) differences occur between African-American and Caucasian patients. METHODS: The study includes ECGs of 2,123 patients, ages 20-99 years attending an urban hospital. RESULTS: First-degree atrioventricular (AV) block was more prevalent in African-American patients compared with Caucasian patients in all age groups of the study except for those patients in the eighth decade of life. The prevalence of first-degree AV block began to increase at age 50 years in both ethnic groups and gradually increased with advancing age, peaking in African-American patients in the 10th decade of life, and in Caucasian patients in the ninth decade of life. The continuing increase in first-degree AV block in African-American patients in the 10th decade of life suggests increasing impairment but greater durability of the AV conduction system in African-American compared with Caucasian patients. The dramatic decline of the prevalence of first-degree AV block in Caucasian patients in the 10th decade of life suggests more frequent failure of the AV conduction system in this group of patients at ages 90-99 years, compared with African-American patients in the same age group. In population-based surveys, first-degree AV block was more prevalent in African-American subjects compared with Caucasian subjects.

Incidence of cardiac sarcoidosis in Japanese patients with high-degree atrioventricular block.

In Japan the majority of sarcoidosis-related deaths are due to cardiac sarcoidosis. One of the most common electrocardiographic abnormalities in patients with this disease is atrioventricular block. This study surveyed the incidence of cardiac sarcoidosis in Japanese patients (40 men and 49 women; mean age, 69.1 years) with high-degree atrioventricular block who were admitted to the hospital to receive a permanent pacemaker. We excluded cases in which sarcoidosis had been diagnosed from the involvement of other organs. Patients with the characteristic signs of sarcoidosis underwent echocardiography, radionuclide imaging, and biopsy. Ten cases (11.2%) of cardiac sarcoidosis were diagnosed, most frequently in women aged 40 to 69 years (8 of 25, 32%). Thus the possibility of cardiac sarcoidosis should be carefully considered in middle-aged or elderly Japanese women who show high-degree atrioventricular block.