Congenital Heart Disease (CHD) is the most common inborn defect. Thanks to medical and surgical advances, over 90% of children with CHD reach adulthood. While syndromes like Di George or CHARGE syndrome are known to be associated with immune deficiencies (1), there is a lack of data regarding the prevalence, clinical characteristics, and prognostic implications of immune deficiencies in patients with CHD.
Using administrative data from one of the largest German insurance companies, Diller et al identified the congenital heart population (2). Patients with HIV infection and autoimmune diseases were excluded. Each patient was then categorized into one of the following groups: confirmed immune defect (ID), presence of increased susceptibility to infections (ISI), or no immune defect.
The diagnosis of ID was based on codes related to combined immunodeficiencies (affecting cellular and humoral immunity), syndromic immunodeficiencies (i.e., Di George and CHARGE syndromes), and antibody deficiencies. The diagnosis of ISI was determined by factors such as the frequency of infections or the need for frequent antibiotic therapy. The study period was divided into two parts: the first period (2005-2010) focused on identifying diagnoses, while the second period (2010-2020) involved follow-up to determine the prognostic impact of having ISI or ID.
The primary endpoint of the analysis was all-cause mortality, while secondary endpoints included emergency hospital admission or death and a composite of endocarditis or cancer and death.
Among the 54,449 CHD patients included in the study, 5.6% had confirmed ID and 27.5% had ISI. Only 2.9% of the age-matched general insurance population had confirmed ID, indicating a 1.9-fold increased risk of ID in the CHD population (P < 0.001). CHD patients with ID or ISI were more likely to be male, younger (median age 8 years at ID diagnosis), and to have a patent arterial duct, ventricular septal defect, uncorrected defect, or univentricular heart.
The primary cause of ID was antibody deficiency (73.4%), while ID affecting cellular immunity or asplenia were rare in this population. The main causes of ISI were recurrent sinopulmonary infections, repeated or prolonged antibiotic therapy, and fungal oral infections.
Multivariable Cox proportional-hazard analysis revealed that immunodeficiency was associated with a higher risk of death, major adverse events, and endocarditis compared to CHD patients without immunodeficiency. The presence of ISI (HR 2.14; P < 0.001) or ID (HR 1.77; P = 0.035) were independent predictors of all-cause mortality. Similarly, there was a significant association between the presence of ISI (HR 1.18; P < 0.001) or ID (HR 1.11; P = 0.02) and the risk of emergency hospital admission or death.
Immune deficiencies are more common in congenital patients than in the general population and are associated with an increased risk of morbidity and mortality. These deficiencies are frequently underdiagnosed, and clinicians should be vigilant when encountering syndromes known to be associated with immunodeficiencies and when patients experience frequent infections. In this setting, it is crucial for clinicians to implement preventive strategies against infections during interventions and educate patients about proper hygiene practices and recognizing infectious symptoms. Large-scale screening questionnaires should be implemented, along with collaborations with immunology specialists. There are numerous emerging therapeutic options, and further studies are necessary to gain a better understanding of the pathophysiological mechanisms, ultimately leading to improved recommendations on antibiotic prophylaxis and patient management.
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