Melissa L. Bates

Aortic stiffness can be assessed using aortic pulse wave velocity (PWV), which can be estimated from peripheral arterial waveforms in adults. However, this method has not been validated in children. We sought to determine whether PWV could be feasibly measured by tonometry and accurately derived from arterial waveforms available in critically ill infants and children. Applanation tonometry was used to measure brachio-femoral or carotid-femoral PWV (b/cfPWV) in hospitalized, hemodynamically stable, prepubertal children with an indwelling arterial catheter. Peripheral arterial line waveforms were converted to ascending aortic waveforms using a model-based transfer function. PWV was estimated from the time delays (Δt _f-b ) between forward and backward wave forms of the ascending aortic waveforms and effective reflecting distance (EfRD). We found that the effective reflecting distance (EfRD) calculation used in adults overestimated b/cfPWV in children. We derived a new EfRD equation that yielded better agreement between measured and estimated PWV (R ² = 0.30, p < 0.05). Estimating PWV from arterial waveform data eliminates the need for tonometry, allowing larger samples of infants and children to be included in future studies of cardiovascular disease and development.

Adults with Down syndrome (DS) are two times more likely to be diagnosed with chronic heart failure post-anthracycline chemotherapy compared to age and sex-matched adults without DS. They have an elevated lifetime risk of cardiovascular diseases, increasing their likelihood of anthracycline-induced chronic cardiovascular toxicity. We investigated the chronic effects of daunorubicin on the cardiovascular system of the adult Ts65Dn mouse model of DS compared to wild type euploid mice (WT). WT and Ts65Dn mice received two doses of 2mg/kg or 4mg/kg of daunorubicin or saline and were monitored for up to 117 days. Cardiac and vascular function were evaluated using left ventricular catheterization, histology, pulse wave velocity, and cardiac troponin tests. Survival significantly decreased in the Ts65Dn 4mg/kg group compared to saline controls (p<0.001). Further experiments were carried out with the saline and 2mg/kg groups, which exhibited lower mortality, more consistent with chronic toxicity. Body weight (p=0.001), end-diastolic pressure (p=0.016), and left ventricular mass (p=0.021) decreased in treated mice. The effect of treatment differed significantly between strains for ejection fraction (p=0.029). Pulse wave velocity increased over time (p<0.001). A significant interaction between treatment and strain was observed for collagen in both the left ventricles and thoracic aorta (p=0.002 and p<0.001, respectively). There was a strain difference for cardiac troponin I, indicating an increase in Ts65Dn mice (p=0.020). Daunorubicin treatment results in a distinct cardiovascular remodeling phenotype in Ts65Dn mice. More mechanistic studies are warranted to outline the pathophysiology of anthracycline cardiovascular toxicity in DS.

Aortic stiffness can be measured using aortic pulse wave velocity (PWV), calculated from peripheral arterial waveforms. However, this method has not been validated in children. We sought to determine whether PWV could be feasibly measured by tonometry and accurately derived from the arterial waveforms available in critically ill infants and children. Applanation tonometry was used to measure brachio-femoral or carotid-femoral PWV (b/cfPWV) in hospitalized hemodynamically stable, pre-pubertal children with an indwelling arterial catheter. Peripheral arterial line waveforms were converted into ascending aortic waveforms by a model transfer function. We found that the effective reflecting distance (EfRD) calculation used in adults overestimated b/cfPWV in children. We derived a new EfRD equation that yielded a better agreement between measured and estimated PWV (R² = 0.30, p < 0.05). Estimating PWV from arterial waveforms data eliminates the need for tonometry, allowing larger sample sizes of infants and children to be included in future cardiovascular disease and development studies. NEW AND NOTEWORTHY: Our study provides a method for non-invasively measuring PWV in children using arterial waveforms. We used gold-standard tonometry to measure brachio/carotid-femoral PWV and derived an equation to estimate effective reflecting distance (EfRD) and PWV from the arterial waveforms in a pediatric critical care setting. We determined that PWV can be accurately estimated from arterial waveforms, providing a new tool for studying aortic stiffness in pediatric patients at risk for cardiovascular disease.

The median life expectancy of people with Down syndrome has increased substantially over the past several decades, from 4 years in 1970 to 53 years in 2010. Despite the recent improvement in survival, there is little data about the prevalence of age‐related diseases, including age‐related malignancies, and the impact of standard cancer treatments on cardiovascular health. We retrospectively reviewed medical records for age‐ and sex‐matched patients ≥ 15 years old with and without Down syndrome using the TriNetX platform to identify the prevalence of malignancies and explore cardiovascular outcomes after treatment with anthracyclines. We further stratified the populations into adolescent and young adult (AYA, ages 15–39 years old) and adult (≥ 40 years old) cohorts, given that treatment recommendations can be different. Down syndrome patients in the AYA cohort were more likely to be diagnosed with acute myeloid leukemia (OR 8.9, CI 4.99–15.89, p < 0.001) and lymphoid leukemia (OR 7.33, CI 4.82–11.15, p < 0.001) The adult cohort with Down syndrome was more likely to be diagnosed with myelodysplastic syndromes (OR 12.25, CI 6.41–23.42, p < 0.001), multiple myeloma (OR 1.66, CI 1.06–2.6, p = 0.026), and testicular cancer (OR 2.73, CI 1.32–5.65, p = 0.005). Overall, Down syndrome patients (≥ 15 years old) treated with anthracyclines were more likely to be diagnosed with heart failure (OR 2.14, CI 1.07–4.27, p = 0.042). Our study demonstrates adolescents and adults with down syndrome have a higher predisposition to several malignancies and an increased risk of cardiovascular disease after anthracycline treatment and may require specific screening guidelines to address their unique health risks.

The median life expectancy of people with Down syndrome has increased substantially over the past several decades, from 4 years in 1970 to 53 years in 2010. Despite the recent improvement in survival, there is little data about the prevalence of age-related diseases, including age-related malignancies, and the impact of standard cancer treatments on cardiovascular health. We retrospectively reviewed medical records for age- and sex-matched patients ≥15 years old with and without Down syndrome using the TriNetX platform to identify the prevalence of malignancies and explore cardiovascular outcomes after treatment with anthracyclines. We further stratified the populations into adolescent and young adult (AYA, ages 15-39 years old) and adult (≥40 years old) cohorts, given that treatment recommendations can be different. Down syndrome patients in the AYA cohort were more likely to be diagnosed with acute myeloid (OR 8.9, CI 4.99-15.89, p<0.001) and lymphoid (OR 7.33, CI 4.82-11.15, p<0.001) leukemia. The adult cohort with Down syndrome was more likely to be diagnosed with myelodysplastic syndromes (OR 12.25, CI 6.41-23.42, p<0.001), multiple myeloma (OR 1.66, CI 1.06-2.6, p=0.026), and testicular cancer (OR 2.73, CI 1.32-5.65, p=0.005). Overall, Down syndrome patients (≥15 years old) treated with anthracyclines were more likely to be diagnosed with heart failure (OR 2.14, CI 1.07-4.27, p=0.042). Our study demonstrates adolescents and adults with Down syndrome have a higher predisposition to several malignancies and an increased risk of cardiovascular disease after anthracycline treatment and may require specific screening guidelines to address their unique health risks.

This investigation documents cardiovascular outcomes in mice receiving urethane anesthesia, emphasizing sex as a biological variable, and considering oxygen supplementation during anesthesia. This is the first report of M-curve analysis in rodents as a heart rate-independent variability analysis.

A clear, inclusive, and accurate approach to the collection of demographic information in clinical research and medical practice is critical to understanding the healthcare needs of the specific population. Inclusive demography constitutes appropriate and accurate characterization of an individual’s sexual orientation and gender identity (SOGI) data. Appropriate demography fosters sense of inclusion and belonging for those belonging to medically marginalized communities such as the lesbian, gay, bisexual, transgender, queer, intersex, asexual, and Indigenous Two-Spirit (LGBTQIA2S+) communities and improves health outcomes. Acquiring inclusive demographics in healthcare research is needed for the following critical reasons. First, LGBTQIA2S+ individuals experience undue psychological harm when their identities are not appropriately captured in survey data, promoting further alienation of the LGBTQIA2S+ community in medicine and research. Second, LGBTQIA2S+ populations are disproportionately burdened by several major cardiovascular and cardiovascular-associated diseases, including hypertension and diabetes. Failure to include these populations, and accurately characterize their participation, in research leads to failure to identify associations between identities and disease, resulting in worse health outcomes. Furthermore, this lack of precision in current data for sex, gender, and sexual orientation may lead to inaccurate data for all populations, not just the LGBTQIA2S+ community. Finally, there are currently major political and social threats and attacks on the LGBTQIA2S+ community and, in particular, on transgender and gender-diverse individuals. Proper medical inclusion and advocacy for the LGBTQIA2S+ community by the medical community may help protect the community from further undue harm through creating sense of belonging and reductions in marginalization-related health inequities.

Synopsis: Preterm birth occurs in 10% of all live births and creates challenges to neonatal life, which persist into adulthood. Significant previous work has been undertaken to characterize and understand the respiratory and cardiovascular sequelae of preterm birth, which are present in adulthood, i.e., “late” outcomes. However, many gaps in knowledge are still present and there are several challenges that will make filling these gaps difficult. In this perspective we discuss the obstacles of studying adults born preterm, including (1) the need for invasive (direct) measures of physiologic function; (2) the need for multistate, multinational, and diverse cohorts; (3) lack of socialized medicine in the United States; (4) need for detailed and better-organized birth records; and (5) transfer of neonatal and pediatric knowledge to adult care physicians. We conclude with a discussion on the “future” of studying preterm birth in regards to what may happen to these individuals as they approach middle and older age and how the improvements in perinatal and postnatal care may be changing the phenotypes observed in adults born preterm on or after the year 2000.

Intermittent hypoxia exposures are commonly used in physiology and many investigators use chamber systems to perform these studies. Because of the variety of chamber systems and protocols used, it is important to understand the sources of variability in intermittent hypoxia experiments that can impact reproducibility. We demonstrate sources of variability that come from the animal model, the intermittent hypoxia protocol, and the chamber system that can impact reproducibility.

In patients with Down syndrome (DS), CHD is the leading cause of death 20 yr old. Men with DS live longer than women. It is unknown if sex differences are present in cardiovascular disease and dysregulation in DS across the lifespan. We observed higher risk of hypertension, ischemic heart disease, and cerebrovascular disease in females and a higher risk of CHD in males with DS.