Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Reduced Fetal Cerebral Oxygen Consumption Is Associated With Smaller Brain Size in Fetuses With Congenital Heart Disease
- Sex Differences in Reperfusion in Young Patients With ST-Segment–Elevation Myocardial Infarction: Results From the VIRGO Study
- Low Cardiac Index Is Associated With Incident Dementia and Alzheimer Disease: The Framingham Heart Study
- Cognitive Function in Survivors of Out-of-Hospital Cardiac Arrest After Target Temperature Management at 33°C Versus 36°C
- Expression of Human Tissue Factor Pathway Inhibitor on Vascular Smooth Muscle Cells Inhibits Secretion of Macrophage Migration Inhibitory Factor and Attenuates Atherosclerosis in ApoE−/− Mice
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Reduced Fetal Cerebral Oxygen Consumption Is Associated With Smaller Brain Size in Fetuses With Congenital Heart Disease
The abnormal connections and obstruction of blood flow that characterize congenital heart disease have long been suspected to influence oxygenation of the developing fetal brain. New magnetic resonance imaging technology has provided the means to explore the relationship between fetal cerebral hemodynamics and brain development, and the results of these preliminary investigations provide supportive evidence for a circulatory basis for the delayed maturation of the fetal brain that is increasingly recognized to be an important factor in the pathogenesis of the adverse neurodevelopmental outcomes that complicate neonatal cardiac surgery. We found an average a 10% reduction in the oxygen saturations of ascending aortic blood in fetuses with congenital heart disease. This resulted from disruption of the normal streaming of oxygenated blood from the umbilical vein to the left heart via the ductus venosus and foramen ovale. In addition, fetal oxygen delivery was reduced as a result of lower umbilical venous saturations, presumably caused by abnormal placental function. In fetuses with a single ventricle, oxygen delivery was also affected by reduced umbilical blood flow, which we attributed to the lower cardiac output we found in this setting. Despite the reduction in the oxygen content of ascending aortic blood, there was no increase in cerebral blood flow or oxygen extraction, so cerebral oxygen delivery and consumption were reduced. The reduction in fetal brain oxygenation was associated with smaller brain size, raising the intriguing question of whether maternal oxygen therapy might be used to improve fetal brain development and to protect the brain against white matter injury in congenital heart disease. See p 1313.
Sex Differences in Reperfusion in Young Patients With ST-Segment–Elevation Myocardial Infarction: Results From the VIRGO Study
Previous studies over the years have reported sex disparities in ST-segment–elevation myocardial infarction care. With subsequent aggressive awareness campaigns for the general population over the past decade, and the standardization of process metrics for providers by Centers for Medicare and Medicaid Services, as well, we would anticipate that these gaps would close. However, our recent prospective, geographically diverse study comparing young women with men <55 years of age presenting with ST-segment–elevation myocardial infarction reveal that significant gaps in care persist. Women, similar to men, had cardiac risk factors; women were more likely to be obese, to smoke, to have diabetes mellitus, and to present >6 hours later than men. Most women (86%) presented with typical chest pain, yet fewer eligible women received reperfusion in comparison with men; and, when receiving reperfusion, women had significant delays in door-to-balloon and door-to-needle times in comparison with similarly aged men even after adjusting for sociodemographics, comorbidities, and clinical factors. The delays were exaggerated when women presented to non–percutaneous coronary intervention institutions requiring transfer. Surprisingly, we did not find the primary reason for delay to be recognition, because an equal proportion of men and women received ECGs within 10 minutes. Our study supports a root cause analysis in understanding the technical, process, or logistical reasons for these delays. It highlights the importance of the regionalization of care to direct transport to primary percutaneous coronary intervention facilities, and the development of standards for transfer algorithms to address sex disparities for patients with ST-elevation myocardial infarctions. See p 1324.
Low Cardiac Index Is Associated With Incident Dementia and Alzheimer Disease: The Framingham Heart Study
In this study, we assessed the association between lower cardiac index and both incident dementia and Alzheimer disease among older adults. More than 1000 participants from the Framingham Offspring Cohort were included in the analyses. Participants were ≥60 years of age with no history of clinical stroke, transient ischemic attack, or dementia at baseline. We related cardiac magnetic resonance imaging–assessed cardiac index to incident all-cause dementia and Alzheimer disease using multivariable-adjusted proportional hazard models. Models were adjusted for education, apolipoprotein E4 status, and Framingham Stroke Risk Profile score (ie, age, systolic blood pressure, antihypertensive medication, diabetes mellitus, cigarette smoking, cardiovascular disease, and atrial fibrillation by sex). We found that a lower cardiac index was associated with a higher relative risk of both incident dementia and Alzheimer disease over a median follow-up period of 7.7 years. When we excluded participants with clinically prevalent cardiovascular disease and atrial fibrillation (n=184), a lower cardiac index continued to be associated with a higher relative risk of both dementia and Alzheimer disease. In light of our observation that one third of the cohort had clinically low cardiac index (<2.5 L·min−1·m−2), our findings may have major public health relevance to Alzheimer disease and dementia risk factors and prevention strategies. Future research is necessary to understand the pathway(s) by which low cardiac index increases risk of dementia and Alzheimer disease for the purposes of informing interventions evaluating whether enhancing cardiac index can reduce unhealthy brain aging or the risk of dementia and Alzheimer disease. See p 1333.
Cognitive Function in Survivors of Out-of-Hospital Cardiac Arrest After Target Temperature Management at 33°C Versus 36°C
With improved survival after out-of-hospital cardiac arrest (OHCA), the importance of reporting a successful resuscitation beyond survival rates has increased, with the main goal to have survivors with a good quality of life. Long-term cognitive impairment resulting from cardiac arrest–related brain injury is a common consequence and constitutes an important clinical challenge. This study was part of the Targeted Temperature Management (TTM) trial, which compared controlled temperatures of 33°C and 36°C during the first 24 hours after OHCA and found no difference in mortality or crude neurological outcome. The study, performed in 5 European countries, assessed the possible effects of the targeted temperature on the cognitive functions most commonly affected by circulatory arrest: memory, attention, and executive functions. We also compared cognitive impairment among OHCA patients and control patients suffering an ST-segment–elevation myocardial infarction. We found that cognitive difficulties were common among OHCA patients but to an equal extent among patients treated at 33°C or 36°C, thereby confirming the neutral results of the TTM trial. Cognitive impairment was also common among disease-matched patients with ST-segment–elevation myocardial infarction and may cause difficulties with everyday tasks and a reduced quality of life. Our results confirm previous smaller studies, show that cognitive screening is an important part of modern cardiac arrest follow-up, and stress that these patients may be in need of further support and rehabilitation. The novel finding that the disease-matched patients with ST-segment–elevation myocardial infarction had cognitive difficulties similar to those of the OHCA patients highlights the importance of other factors for cognitive decline among OHCA survivors besides the cardiac arrest itself. See p 1340.
Expression of Human Tissue Factor Pathway Inhibitor on Vascular Smooth Muscle Cells Inhibits Secretion of Macrophage Migration Inhibitory Factor and Attenuates Atherosclerosis in ApoE−/− Mice
Atherosclerosis is a chronic inflammatory disease and the principal cause of death in the West. Mouse models have taught us a great deal about its pathophysiology. This study reveals a novel mechanism in the pathophysiology and suggests new translational preventative strategies. Early steps in atheroma formation include infiltration of arterial walls by lipids, activation of endothelial and smooth muscle cells resulting in chemokine secretion, and recruitment of leukocytes, which initiates atheroma formation. An important chemokine in this process, identified in mice and humans, is macrophage migration inhibitory factor. Similarly, it is already known that tissue factor and thrombin play a role. In this study, we show how both are linked mechanistically and how important they are for atheroma formation. In an atheroma-prone mouse strain, migration inhibitory factor production by medial smooth muscle cells is tissue factor dependent via production of activated serine proteases and signaling through protease-activated receptors. Moreover migration inhibitory factor production by smooth muscle cells is detectable in young mice before atheroma formation, is necessary for atherosclerosis to occur, and is relevant in mice fed either a normal or high-fat diet. A new mouse strain, expressing a cell-tethered fusion protein to inhibit the activity of tissue factor on smooth muscle cells, is almost completely resistant to atheroma formation, despite having elevated plasma lipids comparable to parental strains. The small lesions that develop in these mice are almost devoid of infiltrating leukocytes. Novel compounds to locally inhibit serine protease activity, protease-activated receptor signaling, or chemokine receptors may offer potential avenues to prevent or treat atherosclerosis in humans. See p 1350.
- © 2015 American Heart Association, Inc.
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