Navigating the Sick Heart With a Map of the Brain

There is a windswept hill on the eastern shore of Staten Island, NY, where stands an old hospital building, its boarded-up façade facing The Narrows of New York Harbor pockmarked with broken windows and overrun with creeping vegetation. The faraway glinting glass of towering Manhattan skyscrapers including One World Trade Center is visible on a clear day if you face the water and look over the train tracks to the left. The Verrazano Narrows Bridge glowers at you from the right, carrying more than 200 000 cars across Staten Island every day between New Jersey and New York with many riders never setting foot on the island or knowing about this place. Next to a long cordon of piled traffic barriers that are not obstructing anyone, plaintive street graffiti pleads, as if from the building itself, “WISH YOU WERE HERE.”This site was the US Marine Hospital, part of the US National Public Health Service for 150 years until 1981, and it served primarily commercial and military sailors as well as the public.1 In 1887 its pioneering bacteriology laboratory became a model for infectious disease investigation; later moved to Washington, DC, it eventually become the National Institutes of Health. Eighty years later in the 1960s the head of the cardiovascular program there was Dr Anthony N. Damato, who led a colorful group of immigrants and Americans, most of whom were avoiding the Vietnam War draft in founding what began as the “dog lab,” invasively examining arrhythmias in animals and, later, people. This was the first electrophysiology laboratory in the world. Here Dr Damato, Dr Benjamin Scherlag, and others drew out the heart’s electrical pathways and gleaned insights2,3 that turned observations into intervention. They did this using custom-built fluoroscopy-guided percutaneous catheters, meticulously poring over reams of tracings on toxic-smelling photographic paper with no one dreaming of what electrophysiology would become.1 Here the investigators elucidated the nuances of cardiac electrophysiology and the basis for arrythmias, as well as the effects of medications and ablation. This fundamental understanding is the basis for the entire subspecialty of electrophysiology today and connects an understanding of why arrythmias happen to what we can do to cure them, and it started with clinicians interested in figuring out mechanisms and treatments one pathway at a time.Among children born with congenital heart disease (CHD), approximately 97% will survive to adulthood and number between 1.5 and 2 million individuals in the United States alone.4,5 How a patient with heart disease of childhood progresses in development toward adulthood is an essential consideration of every major step in managing the illness. The predicted functional outcome for a child with CHD predicates essential questions on management and palliation, every medication decision, every interventional catheterization, every surgery. Therefore, the myriad etiologies that place the developing brain at risk in CHD are important. Insufficient cardiac output and oxygenation threaten the adequacy of perfusion and oxygen delivery to the brain.6 Patients with CHD experience vascular dysfunction and thromboembolic or hemorrhage risks that potentiate potential cerebrovascular insults.7,8 Cumulative procedures, cardiopulmonary bypass exposures, episodes of hemodynamic and respiratory instability, neurological events such as seizures,9,10 and neurologically active medication can also cause irreversible change. Add to this potential genetic and cellular migration issues that can affect the ultrastructure of the developing brain and heart.11,12 In excellent cardiac care, the story of the brain the heart supports and functional development into adulthood speaks volumes about a patient’s course.In this issue of Pediatrics, Dagur et al present a systematic review and meta-analysis of published literature on magnetic resonance imaging (MRI) scans of the brain in pediatric patients with CHD.13 Although static MRI images only provide a snapshot of the brain’s status in time, MRI scans have been a modality of choice in neurological assessment of not just the overall appearance of the brain but changes in perfusion and neuronal architecture afforded by diffusion imaging as well as the cumulative burden of microhemorrhages seen by magnetic susceptibility. Brain MRI with diffusion tensor imaging provides granular information on topology and axonal organization important for insights on how congenital and acquired cardiac disease affects long-term brain function and health. The authors analyzed 126 studies on patients from fetal gestation at 24 weeks to age 21 years including both pre- and postoperative populations. Observing the brain over these epochs tells these patients’ stories; the story and relationships between events, findings, and outcomes draw new insights.In the prenatal period significant findings predominantly reveal issues of dysmorphology and neuronal migration. Postnatally these findings persist as well as signs of a difficult transition, hypoxic ischemic injury, intracranial hemorrhage, and strokes. Postoperatively the story continues, adding findings of intraventricular hemorrhage, periventricular leukomalacia, mineralization and hemosiderin deposition from bleeding, microthrombi, and calcification. These are not just observational phenomena but also benchmarks for longitudinal indicators of care progression, predictors for expectant management of the developing patient with CHD, and biomarkers for research. Research in this arena over time will inform the ongoing development of the field as increasing numbers of patients with CHD are not just surviving14 to adulthood but thriving in their jobs and relationships and as parents themselves. Among patients with CHD, 70% of those surviving to adulthood reach age 70 years themselves.Advances in mechanical circulatory support (MCS) in the way of extracorporeal life support and ventricular assist devices are relevant for patients with CHD in terms of their technological advancements and novel implantation in these patients. Given that 45.5% of children face significant functional morbidity after MCS, the data are important as an estimator of existing neurological risk in mechanical circulatory support. Considering that MRI is impossible with MCS devices being unsafe in magnetic fields, anticipatory planning for imaging before and after support may become increasingly important.As the authors mention, associations across different institutions, patient populations and ages, and scanners are limited because of heterogeneity. However, the imaging findings appear replicable across these populations and likely reflect real pathology. Differences in detection rates were observed as an overall prevalence of structural cerebral abnormalities was reported in this series substantively at 50.3% in line with other published data.The work by Dagur et al stresses the relevance of brain imaging in CHD not just in identifying lesions but mapping the histories and functional hurdles of patients with heart disease, much as Dr Damato and his contemporaries started electrophysiology as a specialty by mapping the behavior of electrical pathways. As an aside, the authors have never been to the former Marine Hospital in Staten Island, its description above is another example using of a map15 together with robust site data and multimodal information in understanding something important in medicine. As survival and outcome improvements continue across cardiac care, a foundational understanding of structural brain health appears increasingly important. As cardiac care and imaging both advance, ongoing excellent research in this arena is essential with consistent methodology and common objectives toward optimizing outcomes in this rapidly advancing field.