Heart medicine has made tremendous progress over the past 60 years. Improvements in surgical and interventional procedures have greatly increased the survival rate of children with congenital heart defects: More than 90 percent of those affected reach adulthood. Yet only a minority can be considered cured.

Impaired Body Defense

In addition to moderate and severe congenital heart defects, even mild congenital heart defects can result in a variety of secondary damage and complications that affect more than just the heart. The fact that the body's immune system can also be impaired was previously known primarily for genetic syndromes such as DiGeorge syndrome, Down syndrome or CHARGE syndrome.

A new study based on health care data from Barmer health insurance shows that many more patients with congenital heart defects suffer from impaired body defenses than previously thought. What's more, the results make it clear that this also makes them more susceptible to life-threatening complications.

Data from 54,449 CHD Patients Studied

A team of researchers led by Professor Gerhard-Paul Diller, senior physician at the ACHD Center of Münster University Hospital (UKM), examined the diagnoses and medication prescriptions of a total of 54,449 patients with congenital heart defects who were treated as outpatients or inpatients between 2005 and 2020 and compared them with the data of heart-healthy insured patients of the same age group and gender. People with autoimmune disease were excluded.

Risk Almost Twice as High in CHD

Immune deficiency (ID) had been identified in 5.6 percent of CHD patients, across the spectrum of mild, moderate, and severe congenital heart defects. In the heart-healthy comparison group, by contrast, this was the case in only 2.9 percent.

The researchers were surprised by this result: "It was suspected that immunodeficiencies are partly responsible for the increased risk of early death from a secondary disease or complication in patients with congenital heart defects. We had not anticipated that the risk of immunodeficiency in congenital heart disease would be nearly twice as high as in the general population. In addition, 27.5 percent of CHD patients were diagnosed with a strikingly high incidence of infections. More research is therefore urgently needed to determine whether an immune deficiency is present," says Gerhard-Paul Diller.

Respiratory Diseases Dominate

A deficiency of antibodies had been documented in 74.3 percent of CHD patients with an immunodeficiency. In contrast, immunodeficiencies resulting from a disruption of cells in the white blood cells were comparatively rare.

The diseases diagnosed were mainly respiratory tract infections. Bronchitis, pneumonia, sinusitis, and otitis media were the most common, accounting for 68.5 percent.

In 41.7 percent of the cases studied, the infections required repeated or prolonged antibiotic treatment. Recurrent fungal infections of the oral mucosa were the second most common diagnosis, at 9.1 percent, indicating immunodeficiency.

Life-Threatening Risk Factors

DiGeorge syndrome, Down syndrome and CHARGE syndrome played a comparatively minor role, as Gerhard-Paul Diller points out: "Only 0.19 percent of patients with a diagnosed immune deficiency were affected by DiGeorge syndrome. The heart malformations often associated with this syndrome, such as TGA, were also significantly less common in this group than in the group in which no immunodeficiency had been diagnosed. Far more common were persistent ductus arteriosus botalli (PDA), ventricular septal defect (VSD), uncorrected congenital heart defect, or univentricular heart."

The researchers are particularly concerned by the results of their more in-depth risk analysis. "Immunodeficiency and frequent recurrent infections were found to be significant risk factors for people with congenital heart defects," reports study author Alicia Fischer. "Both, independent of the known risks from sequelae, reoperations and age-related extracardiac disease, led to increased emergency admissions and also deaths," says the cardiologist at the UKM ACHD Center.

Children and Male Patients More Often Affected?

In children with congenital heart defects, immunodeficiency was found significantly more often (8.7 percent) than in ACHD (2.7 percent). Recurrent infections were found in 43.1 percent of children. In the group of adult patients, on the other hand, this was the case in only 8.7 percent.

In addition, the proportion of male CHD patients affected by immunodeficiency syndrome (ID) and greater susceptibility to infection (ISI) was statistically higher than in the unaffected group with congenital heart defects.

"To be sure, increased susceptibility to infection in children is not unusual in itself. The acquired immune system is learning. As a result, infections usually decrease with advancing age. However, the fact that young patients are also more frequently diagnosed with an immunodeficiency syndrome raises questions that need to be researched in greater depth. This could also be related to advances in ID diagnostics. It is therefore possible that an immunodeficiency in the group of ACHD patients remained undetected more often," says study author Professor Astrid Lammers, commenting on the results.

The increased proportion of male patients with this diagnosis also does not necessarily mean that girls and women are less frequently affected by immunodeficiency, according to the pediatric cardiologist at UKM.

Further Research Urgently Needed

"We know from various studies, for example, that the immune system of adolescent and adult males reacts differently due to hormones. Testosterone and estrogens modulate the reaction of the immune system. As a result, infections may proceed differently in men and women. Overall, the results show us that we need to get to the bottom of immune deficiency in patients with congenital heart defects," emphasizes the ACHD specialist. In doing so, she says, research and investigation must be conducted from both a gender-specific and genetic perspective. "More than 350 genetic defects are now associated with immunodeficiency syndrome."

Be More Vigilant

One thing the study clearly shows. Immune deficiency is a serious risk in patients with congenital heart defects. The researchers therefore recommend including ID screening in the physician's follow-up routine. This includes questions about the frequency of infections within a year, the incidence of severe sinus infections, pneumonia, deep skin or organ abscesses, and skin infections caused by thrush, fungi of the genus Candida, as well as questions about a family history of immunodeficiency syndromes or recurrent prolonged treatment with antibiotics. If an immunodeficiency is suspected, referral to immunology specialists should then be made.

"Even though an infection may be unremarkable on its own. If infections occur more frequently in a patient with a congenital heart defect, this may indicate a previously undiagnosed immune deficiency. We need to be more vigilant here and at the same time work more closely with our specialist colleagues who are experts in immune diseases to be able to intervene with suitable therapeutic measures in a well-timed manner," summarizes Gerhard-Paul Diller.