Low Carotid Flow Pulsatility Index Correlates With the Presence of Unruptured Intracranial Aneurysms

Background We assessed cases of incidental unruptured intracranial aneurysm (UIA) discovered on screening magnetic resonance angiography to identify hemodynamic and atherosclerotic risk factors. Methods and Results The data of 1376 healthy older subjects (age range, 31–91 years) without cerebro‐ or cardiovascular diseases who underwent brain magnetic resonance angiography as part of a medical checkup program at a health screening center were examined retrospectively. We looked for an increase in classical risk factors for UIAs (age, sex, hypertension, and smoking) and laboratory data related to lifestyle diseases among subjects with UIAs. Brachial‐ankle pulse wave velocity, central systolic blood pressure, radial augmentation index, and carotid flow pulsatility index were also compared between those with and without UIAs. We found UIAs in 79 (5.7%) of the subjects. Mean age was 67.1±9.0 years, and 55 (70%) were women. Of the 79 aneurysms, 75 (95%) were in the anterior circulation, with a mean diameter of 3.1 mm (range, 2.0–8.0 mm). Subjects with UIAs were significantly older and had more severe hypertension. The carotid flow pulsatility index was significantly lower in subjects with UIAs and negatively and independently correlated with UIAs. Tertile analysis stratified by carotid flow pulsatility index revealed that subjects with lower indices had higher levels of low‐density lipoprotein cholesterol. Conclusions The presence of UIAs correlated with lower carotid flow pulsatility index and elevated low‐density lipoprotein cholesterol in the data from a population of healthy older volunteers. A reduced carotid flow pulsatility index may affect low‐density lipoprotein cholesterol elevation by some molecular pathways and influence the development of cerebral aneurysms. This may guide aneurysm screening indications for institutions where magnetic resonance angiography is not routine.

Wave Reflection at the Origin of a First-Generation Branch Artery and Target Organ Protection

Excessive pressure and flow pulsatility in first-generation branch arteries are associated with microvascular damage in high-flow organs like brain and kidneys. However, the contribution of local wave reflection and rereflection to microvascular damage remains controversial. Aortic flow, carotid pressure, flow and hydraulic power, brain magnetic resonance images, and cognitive scores were assessed in AGES-Reykjavik study participants without history of stroke, transient ischemic attack, or dementia (N=668, 378 women, 69–93 years of age). The aorta-carotid interface was generalized as a markedly asymmetrical bifurcation, with a large parent vessel (proximal aorta) branching into small (carotid) and large (distal aorta) daughter vessels. Local reflection coefficients were computed from aortic and carotid characteristic impedances. The bifurcation reflection coefficient, which determines pressure amplification in both daughter vessels, was low (0.06±0.03). The carotid flow transmission coefficient was low (0.11±0.04) and associated with markedly lower carotid versus aortic flow pulsatility (waveform SD, 7.2±2.0 versus 98.7±21.8 mL/s, P <0.001), pulsatility index (1.8±0.5 versus 4.5±0.6, P <0.001), and pulsatile power percentage (10±4% versus 25±5%, P <0.001). Transmitted as compared to incident pulsatile power (19.0±9.8 versus 35.9±17.8 mW, P <0.001) was further reduced by reflection (−4.3±2.7 mW) and rereflection (−12.5±8.1 mW) within the carotid. Higher carotid flow pulsatility correlated with lower white matter volume (R=−0.130, P <0.001) and lower memory scores (R=−0.161, P <0.001). Marked asymmetry of characteristic impedances at aorta-branch artery bifurcations limits amplification of pressure, markedly reduces absolute and relative pulsatility of transmitted flow and hydraulic power into first-generation branch arteries, and thereby protects the downstream local microcirculation from pulsatile damage.

Analysis of postprocedural microembolic infarctions and global oxygen extraction fraction during balloon-protected carotid artery stenting: Preliminary study

Background: Atherosclerotic carotid stenosis with impaired cerebral perfusion is a risk factor for cerebral ischemia. In major carotid stenoocclusive diseases, increased oxygen extraction fraction (OEF) is associated with ischemic stroke. Balloon-protected carotid artery stenting (CAS) is valuable for high-grade carotid stenosis. However, while balloon-protected CAS can effectively reduce the occurrence of ischemic complications by blocking carotid flow, cerebral hypoperfusion may result in simultaneous cerebral ischemia. We sought to evaluate whether increased OEF during balloon-protected CAS can predict postprocedural microembolic infarction (MI). Methods: Eighty-four patients who underwent balloon-protected CAS were enrolled. Initial, intraprocedural, and postprocedural OEFs were calculated from the cerebral arteriovenous oxygen differences obtained from blood sampled just before the temporary occlusion and reperfusion of the internal carotid artery during and after the procedure. MIs were evaluated by diffusion-weighted imaging (DWI). Patients were classified into two groups based on the presence or absence of new MIs, and the relationship between the OEF and postprocedural MIs was analyzed. Results: New DWI-positive lesions were found in 37 cases (44.0%). Age, signal intensity ratio (SIR) of carotid plaque on T1-weighted black blood magnetic resonance imaging, and intraprocedural OEF were significantly higher in the DWI-positive group. The high SIR and intraprocedural OEF were significantly associated with the development of postprocedural MIs in multivariate analysis. MIs were correlated with the increase in OEF. Conclusion: Increased intraprocedural OEF, obtained by blood sampling during balloon-protected CAS, could predict the incidence of postprocedural MIs. Patients with carotid stenosis could be hemodynamically compromised by carotid flow blockage during balloon-protected CAS.

Higher pulsatile index in carotid arteries is associated with adverse outcomes in patients treated by left ventricular assist device

Introduction Better understanding of vascular changes in patients after implantation of left ventricular assist devices (LVAD) is important to understand and prevent complications of this therapy. Currently, there is substantial lack of data regarding the impact of changes in carotid territory on clinical events in this population. Our aim was to analyze the association between carotid flow patterns and atherosclerotic changes with serious clinical events after LVAD implantation in a prospective single-center study. Methods Eighty five patients were included (Heart mate II, n=34; Heart mate 3, n=51; mean age 55±15 years; 13 women). Pulsatile and resistance indexes were calculated and atherosclerotic changes (Belcaro score) were assessed using triplex ultrasound at the 3rd and 6th month after LVAD implantation. Basic clinical and laboratory data were also included into the analyses. The median follow-up time was 982 days [IQR 472–1431]. Results Pulsatile and resistance index significantly increased between 3rd and 6th month (p=0.036 and p=0.012, respectively). Belcaro score did not change significantly. During the follow-up, 17 patients died, 4 due to stroke. Another 4 patients suffered from non-fatal stroke. Pulsatile index measured at 3rd month was associated with an increased risk of composite outcome of stroke, GIT hemorrhage and all-cause mortality (HR 10.6, 95% CI 2.0–55.2, p=0.005) only in the group of HeartMate 3 patients, while not in patients with HeartMate II (HR 0.96, 95% CI 0.07–12.4, p=0.97), p for interaction between groups 0.04. Association between pulsatile index and the risk of adverse events in patients with HeartMate 3 remained significant after adjustments for age, cause of heart failure and INTERMACS score. Conclusion Among patients after LVAD implantation, assessment of carotid flow patterns, pulsatile index in particular, may identify individuals at increased risk of serious clinical complications. Future studies are needed to understand mechanisms leading to increase flow pulsatility in this population. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministry of Health of the Czech Republic

Evidence for placental-derived iron-nitrosyls in the circulation of the fetal lamb and against a role for nitrite in mediating the cardiovascular transition at birth

Circulating metabolites of nitric oxide, such as nitrite, iron nitrosyls (FeNO), and nitrosothiols, have vasodilatory bioactivity. In both human and sheep neonates, plasma concentrations of these NO metabolite (NOx) concentrations fall >50% within minutes after birth, raising the possibility that circulating NOx plays a role in maintaining low fetal vascular resistance and in the cardiovascular transition at birth. To test whether the fall in plasma NOx concentrations at birth is due to either ligation of the umbilical cord or oxygenation of the fetus to newborn levels, plasma NOx concentrations were measured during stepwise delivery of near-term fetal lambs. When fetal lambs were intubated and mechanically ventilated with 100% O2 to oxygenate the arterial blood while still in utero with the umbilical circulation still intact, there was no change in plasma NOx levels. In contrast, when the umbilical cord was ligated while fetal lambs were mechanically ventilated with O2 levels that maintained fetal arterial blood gases, plasma NOx levels decreased by nearly 50%. Characterization of the individual NOx species in plasma revealed that the overall fall in NOx at birth was attributable mainly to FeNO compounds. Finally, when the typical fall in NOx after birth was prevented by intravenous nitrite infusion, birth-related changes in blood pressure, heart rate, and carotid flow changes were little affected, suggesting the cardiovascular transition at birth is not dependent on a fall in plasma NOx. In conclusion, this study shows FeNO is released from the placenta and that its decline accounts for most of the measured fall in plasma NOx at birth.