Our ability to identify genetic conditions associated with congenital heart defects (CHDs) has increased substantially over the past decade with the advent of more comprehensive genetic testing methodologies, lower costs and increased availability of clinical genetic testing, practice guidelines advocating for the importance of testing, and improvements in genetic health literacy. 1 At the same time, advances in congenital heart care have improved survival, and an increased emphasis on neurodevelopmental assessment and intervention for high‐risk patients has enhanced developmental progress. 2 These advancements all contribute to improvements in quality of life for patients with CHDs, including patients with genetic syndromes. However, fundamental questions about long‐term prognosis in patients with a genetic condition associated with CHD remain.
In this issue of the Journal of the American Heart Association (JAHA), Engsner and colleagues 3 highlight the importance of investigating the long‐term outcomes of patients with genetic syndromes and CHD but also demonstrate how far we have to go in providing more personalized care. The investigators used Swedish health registries to identify patients with CHD over a 47‐year period, ending in 2017. This national study with unbiased ascertainment and lengthy follow‐up was used to identify patients with Down syndrome (DS) and CHD and investigate mortality rates.
There are several characteristics that make DS an excellent prototype for studying the long‐term mortality rate of a genetic condition associated with CHDs. DS is the most common aneuploidy. Characteristic phenotypic features of DS, including dysmorphic facial features, are completely penetrant, meaning that cases do not go unrecognized or get missed at birth. CHDs occur in approximately half of all patients with DS so that a robust cohort can be studied. Indeed, in this study, 3285 patients with DS and CHD were identified. While some genetic syndromes have a wide spectrum of heterogeneous CHDs, there are a small number of characteristic cardiovascular malformations in DS. 4 This should allow deep phenotyping and more precise estimation of outcome based on lesion type and comorbidities.
The study examined 2 birth periods and, not surprisingly, found improvements in survival in patients with CHD born after 1989 whether or not they had DS. When compared with age‐ and sex‐matched controls paired 8 to 1, patients with DS and CHD had a 25‐fold higher mortality risk. When compared with patients with CHD without DS, stratified by complexity of lesion, patients with CHD and DS had a 2‐fold higher mortality rate. Unfortunately, comparison was not able to be made to patients with DS without CHD to better interpret the mortality risk. Compared with either controls or patients with CHD without DS, the mortality risk was the highest in the 1‐ to 9‐year age group.
Health care supervision guidelines are well established for patients with DS. 5 Common medical problems in individuals with DS that may exacerbate cardiac issues include obstructive sleep apnea (50%–79% of patients with DS), respiratory infections (20%–36%), hypo‐ or hyperthyroidism (up to 10% in childhood, with 50% with thyroid disease in adulthood), autoimmune conditions, obesity, and pulmonary hypertension. Identifying opportunities to optimize management for co‐occurrence of CHD and these morbidities may provide methods to improve overall outcomes. There are other medical conditions such as leukemia that independently impact survival in DS; surgical needs in patients with DS with duodenal atresia, Hirschsprung disease, or atlantoaxial instability will also impact survival and may be more complex in patients with DS and CHD. This study has provided a valuable half‐century view of outcomes of patients with DS and CHD. We need a better understanding of the causes of death to develop recommendations for managing the specific comorbidities that characterize patients with DS and CHD.
Can we learn lessons from the complex care needs of patients with DS and CHD that will be useful for other genetic syndromes associated with CHDs? Our ability to provide tailored management based on a patient‐specific risk profile requires us to understand genetic diagnosis, the penetrance of comorbidities, and impact of CHD. 6 Lessons learned from complex care in DS may shine a light on paths to improve management approaches for patients with a variety of genetic syndromes and CHD.
Disclosures
SMW receives funding from the National Institutes of Health (P01 HL134599 and R01 HL164105).
The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.
This manuscript was sent to John L. Jefferies, MD, MPH, Guest Editor, for editorial decision and final disposition.
See Article by Engsner et al.
For Disclosures, see page 2.
References
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