Friday, 19 Jul 2019

You are here

Congenital Heart Block: Dangers Ahead

Children of autoantibody-positive mothers who were born with congenital heart block were at high risk for developing later cardiovascular and autoimmune disorders, as were their siblings, Swedish researchers reported.

In a cohort that included 119 patients with congenital heart block, 16.8% were diagnosed with cardiomyopathy and/or heart failure compared with 0.3% of controls, for a hazard ratio of 70 (95% CI 20.8-235.4), according to Marie Wahren-Herlenius, MD, PhD, and colleagues from the Karolinska Institute in Stockholm. 

In addition, both patients and their siblings had an increased risk for developing any of 15 common autoimmune diseases such as thyroid disease, psoriasis, arthritis, and multiple sclerosis, with hazard ratios of 5.7 (95% CI 2.83-11.69) for patients and 3.6 (95% CI 1.7-8) for siblings, the researchers reported online in Annals of the Rheumatic Diseases.

Congenital heart block is estimated to occur in 1% to 2% of babies born to mothers with anti-Ro/SSA and anti-La/SSB autoantibodies, which cross the placenta and can cause neonatal lupus with third-degree atrioventricular block. The mothers may have been diagnosed with systemic lupus erythematosus or Sjogren's syndrome, although some are asymptomatic.

Most of these children require placement of a pacemaker early in life, but this in turn can increase the likelihood of future cardiomyopathy.

Previous studies have suggested that affected children face various complications, including growth restriction, neuropsychiatric deficits, and rheumatic diseases, which tend to run in families.

To more closely examine long-term outcomes in children with congenital heart block, Wahren-Herlenius and colleagues undertook a cohort study that enrolled 119 patients and 128 siblings born to antibody-positive mothers from 1948 to 2010.

Each patient was matched with 10 controls from the general population (n=1,190) along with siblings of the controls (n=1,071).

Patients' mean age was 7.5 years, and their siblings' mean age was 11.7 years. Mean follow-up was 17.1 years for patients and 18.4 years for the siblings. Total exposure times for patients and siblings were 2,036 and 2,352 years, respectively, while exposure times for the controls and their siblings were 20,078 and 19,534 years.

A total of 14 cases of cardiomyopathy were diagnosed in the congenital heart block group but none among controls (HR >100), and 10 cases of heart failure versus three among controls (HR 34.4, 95% CI 9.5-125.2). Moreover, 46.2% of patients in the heart block group were diagnosed with "other arrhythmias" compared with 0.4% of controls (HR>100). Sick sinus syndrome was detected in 4.2% of patients and 0.1% of controls, while atrial fibrillation and flutter were found in 7.6% of patients.

And "notably," according to the authors, 3.4% of patients had a cerebral infarction compared with 0.08% of controls (HR 39.9, 95% CI 4.5-357.3).

Connective tissue diseases also were increased among patients (2.5% vs 0.3%, HR 7.5, 95% CI 1.7-33.4). "This risk of systemic connective tissue disorders later in life was increased in patients with congenital heart block (6%) as well as their siblings (4%), albeit the risk was relatively low," commented Jill P. Buyon, MD, director of the Division of Rheumatology at NYU Langone Health in New York City.

"This increased risk is likely reflective of inherited genes conferring overall risk of autoimmunity," said Buyon, who was not involved in the study, but whose group has reported on more than 300 patients at NYU's Research Registry for Neonatal Lupus.

Risks also were elevated for multiple infectious diseases:

  • Infections of the skin and subcutaneous tissue: HR 20.1 (95% CI 6.1-66.9, P<0.01)
  • Bacterial infection of unspecified site: HR 14.9 (95% CI 2.5-89.1, P=0.05)
  • Acute bronchitis: HR 9.2 (95% CI 3.7-22.6, P<0.01)
  • Pneumonia: HR 6.4 (95% CI 2.5-16.5, P<0.01)
  • Acute tonsillitis: HR 3.7 (95% CI 1.8-7.7, P<0.01)
  • Acute upper respiratory infections: HR 2.3 (95% CI 1.3-4, P=0.04)

The researchers also considered the impact of pacemaker treatment, and found that it was protective against cerebral infarction (HR 0.1, 95% CI 0.01-0.8) and arrhythmias (HR 0.4, 95% CI 0.1-0.9), but worsened risk for cardiomyopathy/heart failure (HR 3.8, 95% CI 1.1-12.6) and infections (HR 5.5, 95% CI 2.7-11.3).

Several possible reasons may help explain the increased risk of infection in these patients, including the recognized complication of post-pacemaker-implantation infection and risks associated with prematurity, Wahren-Herlenius and colleagues noted.

"This paper is of interest although it is limited by data being derived from a national register," Buyon told MedPage Today.

Nonetheless, "these data will be informative for both physicians and patients dealing with cardiac complications secondary to in utero exposure to maternal anti-Ro antibodies," she said.

The study was supported by the Swedish Research Council, the Swedish Rheumatism Association, the King Gustaf the Vth 80-year Foundation, the Heart-Lung Foundation, the Freemason's in Stockholm Foundation for Children's Welfare, the Stockholm County Council, the Karolinska Institute, and the Torsten and Ragnar Soderberg Foundation.

Wahren-Herlenius and co-authors disclosed no relevant relationships with industry.

Disclosures: 
The author has no conflicts of interest to disclose related to this subject

Add new comment

More Like This

Cardiovascular Disease Increased in Hospitalized Lupus Patients

Systemic lupus erythematosus (SLE) patients who are hospitalized have an increased prevalence of atherosclerotic cardiovascular disease (ASCVD) and its individual phenotypes of coronary artery disease (CAD), peripheral artery disease (PAD), and cerebrovascular disease. 

Pregnancy Outcomes Improve in Lupus

Pregnancy for patients with lupus has long been considered high risk and associated with both medical and obstetric complications, but outcomes have improved over the last 2 decades and continue to improve. The large decline in in-hospital maternal mortality was greater for lupus pregnancies than for non-lupus pregnancies. Findings from a retrospective cohort study are published in Annals of Internal Medicine.

Blinded by the Use of Antimalarials in Lupus?

Editor's note: July 1 - 5, RheumNow is running the best of EULAR 2019 meeting. Hydroxychloroquine (HCQ) will decrease SLE flares improve lipids, decrease clots, improve survival, augment the response to mycophenolate and are the cornerstone of treatment as per the SLE EULAR guidelines presented at EULAR 2019 in Madrid and also published in ARD. But, if you prescribe them long term, will your patients go blind?

Disparities in Lupus Survival

MMWR has published the outcomes from the Georgia Lupus Registry between 2002 and 2016, finding that black women were not only more likely to die from lupus than white lupus patients; but they died on average 13 years earlier (mean age 51.8 and 52.3 years, respectively) than whites (mean age 64.4 and 65.0 years, respectively). Black women with lupus were 3.34 times more likely to die than black women in the general population, while white women with lupus were 2.43 times more likely to die than white women in the general population. None of the white women with lupus died within 5 years of diagnosis, while mortality was elevated for black women from the date of diagnosis on.

DMARD Success in Myositis-Related Interstitial Lung Disease

It is estimated that up to 50% of patients with idiopathic inflammatory myopathy will be complicated by interstitial lung disease, and having ILD may impart a poor prognosis. A recent review of the Johns Hopkins myositis-related ILD cohort has shown that azathioprine and mycophenolate mofetil use is associated improved lung function and less prednisone use.