Neurovascular coupling in severe aortic valve stenosis.

OBJECTIVES: Aortic stenosis (AS) is characterized by obstruction of blood outflow from the left ventricle, which can impair target organ perfusion such as the brain. We hypothesized that hemodynamic changes in AS may lead to dysfunction of cerebral blood flow regulatory mechanisms. The aim of our study was to evaluate neurovascular coupling in patients with AS by Transcranial Doppler ultrasonography. METHODS: Neurovascular coupling was assessed using visually evoked cerebral blood flow velocity responses (VEFR) calculated as relative blood flow velocity changes in the posterior cerebral artery upon visual stimulation. We analyzed peak systolic, mean and end diastolic VEFR in 54 patients with severe AS and 43 controls in 10 consecutive cycles of visual stimulation. Repeated-measures ANOVA test was used to compare cerebral hemodynamic data by group. RESULTS: Patients with AS had significantly higher peak systolic (12.9% ± 5.6% and 10.5% ± 4.5%; p = .009) and mean VEFR (14.4% ± 5.8% and 12.2% ± 4.9%; p = .021) compared to controls, whereas only a tendency for higher end diastolic VEFR was observed (16.7% ± 6.9% and 14.4% ± 6.2%; p = .061). CONCLUSION: We have shown for the first time that patients with severe AS exhibit higher VEFR than controls indicating dysregulation of neurovascular coupling, which can be one of the factors contributing to development of cognitive decline.

An Intermodal Correlation Study among Imaging, Histology, Procedural and Clinical Parameters in Cerebral Thrombi Retrieved from Anterior Circulation Ischemic Stroke Patients.

The precise characterization of cerebral thrombi prior to an interventional procedure can ease the procedure and increase its success. This study investigates how well cerebral thrombi can be characterized by computed tomography (CT), magnetic resonance (MR) and histology, and how parameters obtained by these methods correlate with each other as well as with the interventional procedure and clinical parameters. Cerebral thrombi of 25 patients diagnosed by CT with acute ischemic stroke were acquired by mechanical thrombectomy and, subsequently, scanned by a high spatial-resolution 3D MRI including T1-weighted imaging, apparent diffusion coefficient (ADC), T2 mapping and then finally analyzed by histology. Parameter pairs with Pearson correlation coefficient more than 0.5 were further considered by explaining a possible cause for the correlation and its impact on the difficulty of the interventional procedure and the treatment outcome. Significant correlations were found between the variability of ADC and the duration of the mechanical recanalization, the deviation in average Hounsfield units (HU) and the number of passes with the thrombectomy device, length of the thrombus, its RBC content and many others. This study also demonstrates the clinical potentials of high spatial resolution multiparametric MRI in characterization of thrombi and its use for interventional procedure planning.

Study of correlations between CT properties of retrieved cerebral thrombi with treatment outcome of stroke patients.

BACKGROUND: All the patients with suspected stroke are directed to whole-brain CT scan. The purpose of this scan is to look for early features of ischemia and to rule out alternative diagnoses than stroke. In case of ischemic stroke, CT diagnostics (including CT angiography) is used mainly to locate the occlusion and its size, while the Hounsfield Units (HU) values of the thrombus causing the stroke are usually overlooked on CT scan or considered not important. The aim of this study was to demonstrate that the HU value is relevant and can help in better treatment planning. PATIENTS AND METHODS: There were 25 patients included in the study, diagnosed with ischemic stroke in the middle cerebral artery (MCA) territory. In all patients, systemic thrombolysis was not successful and the mechanical recanalization was needed. The retrieved thrombi were also analyzed histologically for the determination of red blood cells (RBC) proportion. CT of the proximal MCA (M1) segment was analyzed for average HU value and its variability both in the occluded section and the symmetrical normal site. These CT parameters were then statistically studied for the possible correlations with different clinical, histological and procedure parameters using the Linear Regression and the Pearson correlation coefficient. RESULTS: Relevant positive correlations were found between average HU value of thrombus and outcome modified Rankin Scale (mRS), initial mRS, number of passes with thrombectomy device as well as RBC proportion. CONCLUSIONS: Results of the present study suggest that measured HU values in CT images of the cerebral thrombi may help in the assessment of thrombus compaction and therefore better treatment planning.

Clinical and Radiological Characteristics Associated with Respiratory Failure in Unilateral Lateral Medullary Infarction.

BACKGROUND: The prognosis for unilateral lateral medullary infarction (ULMI) is generally good but may be aggravated by respiratory failure with fatal outcome. Respiratory failure has been reported in patients with severe bulbar dysfunction and large rostral medullary lesions, but its associated factors have not been systematically studied. We aimed to assess clinical and radiological characteristics associated with respiratory failure in patients with pure acute ULMI. MATERIALS AND METHODS: Seventy-one patients (median age 55 years, 59 males) with MRI-confirmed acute pure ULMI were studied retrospectively. Clinical characteristics were assessed and bulbar symptoms were scored using a scale developed for this study. MRI lesions were classified into 4 groups based on their vertical extent (localized/extensive) and the involvement of the open and/or closed medulla. Clinical characteristics, bulbar scores and MRI lesion characteristics were compared between patients with and without respiratory failure. RESULTS: Respiratory failure occurred in 8(11%) patients. All patients with respiratory failure were male (p = 0.336), had extensive lesions involving the open medulla (p = 0.061), progression of bulbar symptoms (p=0.002) and aspiration pneumonia (p < 0.001). Peak bulbar score (OR, 7.9 [95% CI, 2.3-160.0]; p < 0.001) and older age (OR, 1.2 [95%CI, 1.0-1.6]; p=0.006) were independently associated with respiratory failure. CONCLUSIONS: Extensive damage involving the open/rostral medulla, clinically presenting with severe bulbar dysfunction, in conjunction with factors such as aspiration pneumonia and older age appears to be crucial for the development of respiratory failure in pure ULMI. Further prospective studies are needed to identify other potential risk factors, pathophysiology, and effective preventive measures for respiratory failure in these patients.

Cerebral microemboli in mini-sternotomy compared to mini- thoracotomy for aortic valve replacement: a cross sectional cohort study.

BACKGROUND: Recently adopted mini-thoracotomy approach for surgical aortic valve replacement has shown benefits such as reduced pain and shorter recovery, compared to more conventional mini-sternotomy access. However, whether limited exposure of the heart and ascending aorta resulting from an incision in the second intercostal space may lead to increased intraoperative cerebral embolization and more prominent postoperative neurologic decline, remains inconclusive. The aim of our study was to assess potential neurological complications after two different minimal invasive surgical techniques for aortic valve replacement by measuring cerebral microembolic signal during surgery and by follow-up cognitive evaluation. METHODS: Trans-cranial Doppler was used for microembolic signal detection during aortic valve replacement performed via mini-sternotomy and mini-thoracotomy. Patients were evaluated using Addenbrooke's Cognitive Examination Revised Test before and 30 days after surgical procedure. RESULTS: A total of 60 patients were recruited in the study. In 52 patients, transcranial Doppler was feasible. Of those, 25 underwent mini-sternotomy and 27 had mini-thoracotomy. There were no differences between groups with respect to sex, NYHA class distribution, Euroscore II or aortic valve area. Patients in mini-sternotomy group were younger (60.8 ± 14.4 vs.72 ± 5.84, p = 0.003), heavier (85.2 ± 12.4 vs.72.5 ± 12.9, p = 0.002) and had higher body surface area (1.98 ± 0.167 vs. 1.83 ± 0.178, p = 0.006). Surgery duration was longer in mini-sternotomy group compared to mini-thoracotomy (158 ± 24 vs. 134 ± 30 min, p < 0.001, respectively). There were no differences between groups in microembolic load, length of ICU or total hospital stay. Total microembolic signals count was correlated with cardiopulmonary bypass duration (5.64, 95%CI 0.677-10.60, p = 0.027). Addenbrooke's Cognitive Examination Revised Test score decreased equivalently in both groups (p = 0.630) (MS: 85.2 ± 9.6 vs. 82.9 ± 11.4, p = 0.012; MT: 85.2 ± 9.6 vs. 81.3 ± 8.8, p = 0.001). CONCLUSION: There is no difference in microembolic load between the groups. Total intraoperative microembolic signals count was associated with cardiopulmonary bypass duration. Age, but not micorembolic signals load, was associated with postoperative neurologic decline. TRIAL REGISTRY NUMBER: clinicaltrials.gov , NCT02697786 14.

Cerebral blood flow impairment and cognitive decline in heart failure.

BACKGROUND AND PURPOSE: Cognitive decline is an important contributor to disability in patients with chronic heart failure, affecting 25%-50% of patients. The aim of this review is to stress the importance of understanding pathophysiological mechanisms of heart failure involved in cognitive decline. METHODS: An extensive PubMed search was conducted for the literature on the basic mechanisms of cerebral blood flow regulation, the effect of cardiac dysfunction on cerebral blood flow, and possible mechanisms underlying the association between cardiac dysfunction and cognitive decline. RESULTS: Published literature supports the thesis that cardiac dysfunction leads to cerebral blood flow impairment and predisposes to cognitive decline. One of the postulated mechanisms underlying cognitive decline in chronic heart failure is chronic regional hypoperfusion of critical brain areas. Cognitive function may be further compromised by microvascular damage due to cardiovascular risk factors. Furthermore, it is implied that cerebral blood flow assessment could enable early recognition of patients at risk and help guide appropriate therapeutic strategies. CONCLUSION: Interdisciplinary knowledge in the fields of neurology and cardiology is essential to clarify heart and brain interconnections in chronic heart failure. Understanding and identifying the basic neuropathophysiological changes in chronic heart failure could help with developing methods for early recognition of patients at risk, followed by institution of therapeutic actions to prevent or decrease cognitive decline.

Novel Direct Anticoagulants and Atherosclerosis.

Coagulation factors can affect cellular processes that include inflammatory signaling by acting on endothelial protease activated receptors, vascular smooth muscle and inflammatory cells beyond the coagulation cascade. This is important in the pathogenesis of atherosclerosis. Accordingly, experimental data points to beneficial effects of coagulation protease inhibitors on the attenuation of atherosclerosis progression in animal models. However, available clinical data do not support the use of anticoagulants as an add-on treatment of atherosclerosis. New clinical studies are needed with a better selection of patients to clarify the role of novel direct anticoagulants in the management of atherosclerosis.

Is there a persistent dysfunction of neurovascular coupling in migraine?

Changes in cerebral blood flow are one of the main features of migraine attack and have inspired the vascular theory of migraine. This traditional view has been reshaped with recent experimental data, which gave rise to the neural theory of migraine. In this review, we speculate that there might be an important link between the two theories, that is, the dysfunction of neurovascular coupling.

Study of neurovascular coupling during cold pressor test in patients with migraine.

BACKGROUND: Altered neurovascular coupling in migraineurs could be a consequence of impaired function of modulatory brainstem nuclei. The cold pressor test (CPT) should activate brainstem structures. We measured visually evoked cerebral blood flow velocity response (VEFR) to CPT in migraine. METHODS: Twenty-three healthy volunteers and 29 migraineurs participated in the study. We measured arterial blood pressure, end-tidal CO2, heart rate and cerebral blood flow velocity in posterior and middle cerebral artery using transcranial Doppler. VEFR was calculated as cerebrovascular reactivity to photic stimulation before, during and after CPT. RESULTS: In healthy individuals, there was a significant decrease in peak systolic VEFR from CPT phase to recovery phase (p < 0.05). There was an increase in mean VEFR from basal to CPT phase and a decrease from CPT to recovery phase, both significant (p < 0.05). End-diastolic VEFR increased from basal to CPT phase and decreased in recovery phase below the basal phase values, all changes significant (p < 0.05). In migraine, no statistically significant changes in peak systolic, mean or end-diastolic VEFRs were observed between phases (p > 0.05). The differences in phases in mean and end-diastolic VEFRs between the basal phase and the CPT phase and between the CPT phase and the recovery phase were significantly higher in healthy individuals (p < 0.05). CONCLUSIONS: The absence of the effect of CPT on VEFR in migraine is likely to be a consequence of impaired subcortical modulation of neurovascular coupling.

Impact of altered venous hemodynamic conditions on the formation of platelet layers in thromboemboli.

Although it is generally believed that the structure of venous thromboemboli is a homogeneous red blood cell-fibrin clot, their structure may be heterogeneous, with non-uniformly distributed platelet layers, known as the lines of Zahn. We tested (a) whether venous thromboemboli ex vivo contained platelet layers, i.e. the lines of Zahn, and (b) whether, according to mathematical modeling, eddies can arise in the venous system, possibly contributing to platelet aggregation. The structure of venous thromboemboli ex vivo was determined by high-resolution magnetic resonance imaging (MRI) and by immunohistochemistry (IHC). High-resolution ultrasound (US) imaging was employed to determine the popliteal vein geometry and hemodynamics in healthy subjects and in subjects with previous venous thrombosis. The US data were then used as input for numerical simulations of venous hemodynamics. MRI and IHC confirmed that 42 of 49 ex vivo venous thromboemboli were structurally heterogeneous with platelet layers. The peak venous flow velocity was higher in patients with partly recanalized deep vein thrombosis than in healthy subjects in the prone position (46±4cm/s vs. 16±3cm/s). Our numerical simulation showed that partial venous obstruction with stenosis or malfunctioning venous valves creates the conditions for eddy blood flow. Our experimental results and computer simulation confirmed that the heterogeneous structure of venous thromboemboli with twisted platelet layers may be associated with eddy flow at the sites of their formation.

The effect of the cold pressor test on a visually evoked cerebral blood flow velocity response.

We investigated the hypothesis that during tonic pain stimulus, neurovascular coupling (NVC) decreases, measuring visually evoked cerebral blood flow velocity response (VEFR) during cold pressor test (CPT) in healthy human subjects as a test. VEFR was calculated as a relative increase in blood flow velocity in the posterior cerebral artery from average values during the last 5 s of the stimulus-OFF period to average values during the last 10 s of the stimulus-ON period. Three consecutive experimental phases were compared: basal, CPT and recovery. During CPT, end-diastolic and mean VEFR increased from 20.2 to 23.6% (p < 0.05) and from 17.5 to 20.0% (p < 0.05), respectively. In recovery phase, end-diastolic and mean VEFR decreased to 17.7% and 15.5%, respectively. Both values were statistically significantly different from CPT phase (p < 0.05). Compared with the basal phase, only end-diastolic VEFR was statistically significantly different in the recovery phase (p < 0.05). Our results are consistent with the assumption that there is a change in the activity of NVC during CPT because of the modulatory influence of subcortical structures activated during tonic pain. Contrary to our expectations, the combined effect of such influences increases rather than decreases NVC.