Abstract P152: Low Memory Recall And High Common Carotid Artery Flow Pulsatility In Non-Dialysis Chronic Kidney Disease Patients

A significant proportion of patients with non-dialysis chronic kidney disease (CKD) present with mild-to-moderate deficits in the cognitive domains of executive function and episodic memory. Excess blood flow pulsatility is damaging to the microvasculature of high-flow, low-resistance organs like the brain and may contribute to the cognitive deficits prevalent among CKD patients. We tested the hypothesis that patients with moderate-to-severe non-dialysis CKD have excess flow pulsatility along their carotid and cerebral vasculature that is associated with deficits in executive function and episodic memory. We recruited 10 non-dialysis CKD patients (age=68±8 yrs; estimated glomerular filtration rate, eGFR=36±18 mL/min/1.73 m 2 ) and 7 healthy age-matched adults (age=65±5 yrs; eGFR=81±17 mL/min/1.73 m 2 ). Global cognitive function was assessed with the Montreal Cognitive Assessment (MoCA). Executive function and episodic memory were assessed using the NIH Toolbox Flanker Inhibitory Control and Attention Test and California Verbal Learning Test III, respectively, and reported as standardized scores (mean=100, SD=15). Pulsatility index [(systolic blood velocity - diastolic blood velocity)/ mean blood velocity] was measured in the common carotid (CCA), internal carotid (ICA), and middle cerebral arteries (MCA) via Doppler and transcranial Doppler ultrasound. Compared to healthy adults, CKD patients did not differ in total brain blood flow (p=0.42) but had lower MoCA (CKD=26±3, Healthy=29±1; p=0.01) and memory recall scores (CKD=92±21, Healthy=110±9; p=0.05). CKD patients did not differ from our healthy control group in executive function (CKD=91±10, Healthy=90±11; p=0.80) but did produce a mean score that was 0.6 SD lower than the NIH Toolbox reference sample. CKD patients had a higher pulsatility index in the CCA (CKD=2.3±0.5, Healthy=1.9±0.3; p=0.05) but not in the ICA (p=0.68) or MCA (p=0.57). CCA pulsatility index was strongly and inversely associated with episodic memory recall scores (r=-0.64, p<0.01, n=17). This data suggests that although the higher CCA flow pulsatility in non-dialysis CKD patients does not appear to be transmitted to the cerebrovasculature, it nevertheless may still be contributing to memory impairments.

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.

Does Maintenance of Pulmonary Blood Flow Pulsatility at the Time of the Fontan Operation Improve Hemodynamic Outcome in Functionally Univentricular Hearts?

It is unclear whether residual anterograde pulmonary blood flow (APBF) at the time of Fontan is beneficial. Pulsatile pulmonary flow may be important in maintaining a compliant and healthy vascular circuit. We, therefore, wished to ascertain whether there was hemodynamic evidence that residual pulsatile flow at time of Fontan promotes clinical benefit. 106 consecutive children with Fontan completion (1999–2018) were included. Pulmonary artery pulsatility index (PI, (systolic pressure–diastolic pressure)/mean pressure)) was calculated from preoperative cardiac catheterization. Spectral analysis charted PI as a continuum against clinical outcome. The population was subsequently divided into three pulsatility subgroups to facilitate further comparison. Median PI prior to Fontan was 0.236 (range 0–1). 39 had APBF, in whom PI was significantly greater (median: 0.364 vs. 0.177, Mann–Whitney p < 0.0001). There were four early hospital deaths (3.77%), and PI in these patients ranged from 0.214 to 0.423. There was no correlation between PI and standard cardiac surgical outcomes or systemic oxygen saturation at discharge. Median follow-up time was 4.33 years (range 0.0273–19.6), with no late deaths. Increased pulsatility was associated with higher oxygen saturations in the long term, but there was no difference in reported exercise tolerance (Ross), ventricular function, or atrioventricular valve regurgitation at follow-up. PI in those with Fontan-associated complications or the requiring pulmonary vasodilators aligned with the overall population median. Maintenance of pulmonary flow pulsatility did not alter short-term outcomes or long-term prognosis following Fontan although it tended to increase postoperative oxygen saturations, which may be beneficial in later life.

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.