Principles and pitfalls in coronary vasomotor function testing.

BACKGROUND: Coronary vasomotor dysfunction can be diagnosed in a large proportion of patients with angina in the presence of non-obstructive coronary artery disease (ANOCA) using comprehensive protocols for coronary vasomotor function testing (CFT). Although consensus on diagnostic criteria for endotypes of coronary vasomotor dysfunction has been published, consensus on a standardised study testing protocol is lacking. AIMS: In this review we provide an overview of the variations in CFT used and discuss the practical principles and pitfalls of CFT. METHODS: For the purposes of this review, we assessed study protocols that evaluate coronary vasomotor response as reported in the literature. We compared these protocols regarding a number of procedural aspects and chose six examples to highlight the differences and uniqueness. RESULTS: Currently, numerous protocols co-exist and vary in vascular domains tested, the manner in which to test these domains (e.g., preprocedural discontinuation of medication, provocative agent, solution, infusion time, and target artery) and techniques used for measurements (e.g., Doppler vs thermodilution technique). CONCLUSIONS: This lack of consensus on a uniform functional testing protocol hampers both a broader clinical acceptance of the concepts of coronary vasomotor dysfunction, and the widespread adoption of such testing protocols in current clinical practice. Furthermore, the endotype of coronary vasomotor dysfunction might differ among the few specialised centres that perform CFT as a result of the use of different protocols.

Cerebral hemodynamic alterations in patients with Covid-19

Background/aim: Coronavirus 2019 disease (Covid-19) was first seen in December 2019 and afterwards it became pandemic. Several systemic involvements have been reported in Covid-19 patients. In this study, it was aimed to investigate the cerebrovascular hemodynamics in patients with Covid-19. Materials and methods: The sample of this study included 20 patients hospitalized in our clinic diagnosed with Covid-19 via PCR modality and 20 healthy volunteers of similar age and sex. Bilateral middle cerebral arteries were investigated with transcranial Doppler ultrasonography. Basal cerebral blood flow velocities and vasomotor reactivity rates were determined and statistically compared. Results: When patient and control groups were compared, the mean blood flow velocity was found to be higher in Covid-19 patients than in the healthy volunteers and it was statistically significant (P = 0.00). The mean vasomotor reactivity rates values were found to be lower in the Covid-19 group than the healthy group and was also statistically significant (P = 0.00). Conclusion: An increase in basal cerebral blood velocity and a decrease in vasomotor reactivity rates in patients with Covid-19 can be considered as an indicator of dysfunction of cerebral hemodynamics in the central nervous system and this can be evaluated as a result of endothelial dysfunction.

Asymmetric dimethylarginine predicts impaired epicardial coronary vasomotion in patients with angina in the absence of obstructive coronary artery disease.

BACKGROUND: Impaired epicardial coronary vasomotion is a potential mechanism of angina and a predictor of adverse cardiovascular outcomes in patients without angiographic evidence of obstructive coronary artery disease (CAD). We sought to evaluate the association of asymmetric dimethylarginine (ADMA)-a marker of nitric oxide-mediated vascular dysfunction-with epicardial coronary vasomotor dysfunction in this select population. METHODS: Invasive testing for epicardial vasomotor dysfunction was performed using intracoronary acetylcholine in the left anterior descending coronary artery. Impaired vasomotor response was defined as a luminal constriction of >20% on quantitative coronary angiography. Plasma ADMA levels were measured using high performance liquid chromatography. A robust multivariate linear mixed-effect model approach and Akaike information criterion were used to determine predictors of vasomotor dysfunction. RESULTS: In 191 patients with angina in the absence of obstructive CAD, abnormal epicardial vasomotion was observed in 137 (71.7%) patients. Median ADMA rose as the extent of impairment progressed: none (0.48 [0.44-0.59] µM), any (0.51 [0.46-0.60] µM, p = 0.12), focal (0.54 [0.49,0.61] µM, p = 0.17), and diffuse (0.55 [0.49,0.63] µM, p = 0.02). In unadjusted analysis, ADMA was highly predictive of vasomotor dysfunction (χ2=15.1, p = 0.002). Notably, ADMA remained a significant predictor even after adjusting for other factors in the best fit model (χ2=10.0, p = 0.02). CONCLUSIONS: ADMA is an independent predictor of epicardial coronary vasomotor dysfunction in patients with angina in the absence of obstructive CAD. These data support a very early mechanistic role of ADMA in the continuum of atherosclerotic heart disease.

Persistent Dysfunction of Coronary Endothelial Vasomotor Responses is Related to Atheroma Plaque Progression in the Infarct-Related Coronary Artery of AMI Survivors.

AIM: Although coronary endothelial vasomotor dysfunction predicts future coronary events, there are few human studies showing the relationship between endothelial vasomotor dysfunction and atheroma plaque progression in the same coronary artery. This study examined whether endothelial vasomotor dysfunction is related to atheroma plaque progression in the infarct-related coronary artery of ST-segment elevation myocardial infarction (STEMI) survivors using serial assessment of coronary plaque size with intravascular ultrasound (IVUS) and coronary vasomotor responses to acetylcholine (ACh). METHODS: This study included 50 patients with a first acute STEMI due to occlusion of the left anterior descending coronary artery (LAD) and successful reperfusion therapy with percutaneous coronary intervention (PCI). IVUS and vasomotor response to ACh in the LAD were measured within two weeks of acute myocardial infarction (AMI) (1st test) and repeated six months (2nd test) after AMI under optimal anti-atherosclerotic therapies. RESULTS: Percent atheroma volume (PAV) and total atheroma volume (TAV) in the LAD progressed over six months of follow-up in 18 and 14 patients, respectively. PAV and TAV progression was significantly associated with persistent impairment of epicardial coronary artery dilation and coronary blood flow increase in response to ACh at both the 1st and 2nd tests. PAV and TAV progression had no significant association with traditional risk factors, PCI-related variables, medications, and the coronary vasomotor responses to sodium nitroprusside, an endothelium-independent vasodilator. CONCLUSIONS: Persistent impairment of endothelial vasomotor function in the conduit arterial segment and the resistance arteriole was related to atheromatous plaque progression in the infarct-related coronary arteries of STEMI survivors.

Effects of neuropeptide Y on coronary artery vasomotion in patients with microvascular angina.

BACKGROUND: Patients with microvascular angina (exertional angina, positive exercise tests and normal coronary arteriograms) usually have a reduced coronary blood flow reserve. Neuropeptide Y (NPY) is a potent endogenous vasoconstrictor involved in modulation of coronary vasomotor tone and may play a role in microvascular angina. METHODS: We compared the effects of NPY (0.2-1.0pmol/kg, intracoronary) on the vasomotor response of proximal and distal segments of the coronary arteries in 7 patients with microvascular angina, 9 with chronic stable angina, and 9 control individuals. The coronary response to the administration of ergonovine was also assessed in 9 other patients with microvascular angina. Computerized coronary artery diameter measurements were carried out before (baseline) and after the administration of the vasoactive agents. RESULTS: Mean baseline coronary lumen diameters were similar in control, microvascular angina, and coronary artery disease patients. NPY constricted proximal coronary segments by 8±2%, 5±2% and 6±3% and distal segments by 14±2%, 11±2% and 10±2% in control, microvascular angina, and coronary artery disease patients, respectively (p=NS between groups). In patients with microvascular angina, ergonovine constricted proximal coronary segments by 7±1.5% and distal segments by 12.5±3% (p=NS vs. NPY). During NPY administration four microvascular angina patients developed chest pain, ST segment depression, and a marked lengthening of the contrast medium run off, in the absence of epicardial coronary artery spasm. Control individuals and coronary artery disease patients did not experience chest pain, ST segment shifts, or lengthening of the run off during NPY administration. Ergonovine administration caused chest pain and lengthening of the contrast run-off, in the absence of epicardial coronary artery spasm, in one microvascular angina patient. CONCLUSIONS: Exogenous NPY causes mild epicardial coronary artery constriction which is similar in patients with non-cardiac chest pain, microvascular angina and coronary artery disease. Myocardial ischemia and marked lengthening of the contrast run off in response to NPY occurred in microvascular angina patients but not in control or coronary artery disease patients. An abnormal constrictor response to NPY at the microcirculation level could be the mechanism underlying the ischemic manifestations observed in patients with microvascular angina. CONDENSED ABSTRACT (TABLE OF CONTENTS): The vasomotor response of proximal and distal coronary artery segments was studied in twenty five patients: 7 microvascular angina, 9 chronic stable angina, and 9 control subjects. Computerized measurements of coronary diameters were carried out before and after the intracoronary administration of neuropeptide Y (NPY) and ergonovine. Constriction of epicardial arteries in response to NPY was mild and not significantly different in control, microvascular angina and coronary artery disease patients. Ergonovine-induced epicardial coronary artery constriction was similar to that of NPY. However, NPY caused transient myocardial ischemia in patients with microvascular angina (probably through constriction of the small intramyocardial vessels), but not in control subjects or coronary artery disease patients.

Rat retinal vasomotion assessed by laser speckle imaging.

Vasomotion is spontaneous or induced rhythmic changes in vascular tone or vessel diameter that lead to rhythmic changes in flow. While the vascular research community debates the physiological and pathophysiological consequence of vasomotion, there is a great need for experimental techniques that can address the role and dynamical properties of vasomotion in vivo. We apply laser speckle imaging to study spontaneous and drug induced vasomotion in retinal network of anesthetized rats. The results reveal a wide variety of dynamical patterns. Wavelet-based analysis shows that (i) spontaneous vasomotion occurs in anesthetized animals and (ii) vasomotion can be initiated by systemic administration of the thromboxane analogue U-46619 and the nitric-oxide donor S-nitroso-acetylDL-penicillamine (SNAP). Although these drugs activate different cellular pathways responsible for vasomotion, our approach can track the dynamical changes they cause.

Is cerebral vasomotor reactivity impaired in Parkinson disease?

PURPOSE: The ability of a blood vessel to change diameter in response to a change in carbon dioxide concentration is often referred to as vasomotor reactivity. This study aimed to determine whether vasomotor reactivity is impaired in patients with idiopathic Parkinson's Disease in comparison to healthy controls. METHODS: Transcranial Doppler was used to measure cerebral blood flow velocity in the middle cerebral arteries at baseline and under hypocapnic conditions in 40 patients with idiopathic Parkinson's disease and 50 healthy controls. RESULTS/CONCLUSIONS: Vasomotor reactivity, assessed under hypocapnic conditions, is not impaired in patients with idiopathic Parkinson's Disease in comparison to healthy controls.

Cerebral vasomotor reactivity assessment using Transcranial Doppler and MRI with apnea test.

Differently from previous studies that used Transcranial Doppler (TCD) and functional MRI (fMRI) for cerebral vasomotor reactivity (CVR) assessment in patients with carotid stenosis (CS), we assessed CVR using an identical stimulus, the Breath-Holding Test (BHT). We included 15 patients with CS and 7 age-matched controls to verify whether fMRI responded differently to BHT between groups and to calculate the agreement rate between tests. For TCD, impaired CVR was defined when the mean percentage increase on middle cerebral artery velocities was ≤31% on 3 consecutive 30-s apnea intercalated by 4-min normal breathing intervals. For fMRI, the percent variation on blood oxygen level-dependent (BOLD) signal intensity in the lentiform nucleus (LN) ipsilateral to the CS (or both LNs for controls) from baseline breathing to apnea was measured. The Euclidian differences between the series of each subject and the series of controls and patients classified it into normal or impaired CVR. We found different percent variations on BOLD-signal intensities between groups (P=0.032). The agreement was good in Controls (85.7%; κ=0.69) and overall (77.3%; κ=0.54). We conclude that BHT was feasible for CVR assessment on fMRI and elicited different BOLD responses in patients and controls, with a good overall agreement between the tests.

Systemic arterial stiffness in infants with bronchopulmonary dysplasia: potential cause of systemic hypertension.

OBJECTIVE: Systemic hypertension is common among preterm infants with severe bronchopulmonary dysplasia (BPD); the exact cause is unknown. The objective of this preliminary hypothesis generating study was to examine systemic arterial structure and vasomotor function in a cohort of preterm infants with severe BPD, using a cohort of preterm infants without BPD and a cohort of term infants for comparison. STUDY DESIGN: After obtaining informed consent, we measured aortic wall thickness and vasomotor function by ultrasonography in 20 infants with severe BPD, 7 infants with no BPD, and compared them with 20 healthy term infants. RESULTS: Maximum aortic thickness was significantly higher in infants with BPD (827±163 µm) compared to those with no BPD (674±22 µm) and term infants (657±67 µm) (unadjusted P<0.0001). The input impedance was similarly elevated in the infants with BPD (574±127 dynes s( )cm(-5)) compared to those with no BPD (325±24 dynes s cm(-)(5)) or term infants (328±113 dynes s cm(-)(5)) (unadjusted P<0.0001). Stiffness index was significantly higher in the infants with BPD (3.4±0.6) compared to those with no BPD (2.6±0.3) or term infants (2.3±0.4) (unadjusted P<0.0001). Systemic vascular resistance was also significantly elevated in the infants with BPD. The results remained significant even after adjusting for gestational age and birth weight. Measures of vasomotor function significantly correlated with blood pressure. CONCLUSION: The aortic wall thickness and vasomotor function are significantly altered in preterm infants with severe BPD. These findings may explain the higher incidence of systemic hypertension in this population.

Detecting gas-induced vasomotor changes via blood oxygenation level-dependent contrast in healthy breast parenchyma and breast carcinoma.

PURPOSE: To evaluate blood oxygenation level-dependent (BOLD) contrast changes in healthy breast parenchyma and breast carcinoma during administration of vasoactive gas stimuli. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) was performed at 3T in 19 healthy premenopausal female volunteers using a single-shot fast spin echo sequence to acquire dynamic T2 -weighted images. 2% (n = 9) and 5% (n = 10) carbogen gas mixtures were interleaved with either medical air or oxygen in 2-minute blocks, for four complete cycles. A 12-minute medical air breathing period was used to determine background physiological modulation. Pixel-wise correlation analysis was applied to evaluate response to the stimuli in breast parenchyma and these results were compared to the all-air control. The relative BOLD effect size was compared between two groups of volunteers scanned in different phases of the menstrual cycle. The optimal stimulus design was evaluated in five breast cancer patients. RESULTS: Of the four stimulus combinations tested, oxygen vs. 5% carbogen produced a response that was significantly stronger (P < 0.05) than air-only breathing in volunteers. Subjects imaged during the follicular phase of their cycle when estrogen levels typically peak exhibited a significantly smaller BOLD response (P = 0.01). Results in malignant tissue were variable, with three out of five lesions exhibiting a diminished response to the gas stimulus. CONCLUSION: Oxygen vs. 5% carbogen is the most robust stimulus for inducing BOLD contrast, consistent with the opposing vasomotor effects of these two gases. Measurements may be confounded by background physiological fluctuations and menstrual cycle changes. J. Magn. Reson. Imaging 2016;44:335-345.

Late gadolinium enhancement on cardiac magnetic resonance predicts coronary vasomotor abnormality and myocardial lactate production in patients with chronic heart failure.

Myocardial fibrosis and microvascular dysfunction are key determinants of outcome in heart failure (HF); we examined their relationship in patients with HF. Our study included 61 consecutive patients with HF but without coronary stenosis. All underwent gadolinium-enhanced cardiac magnetic resonance to evaluate late gadolinium enhancement (LGE) and an acetylcholine (ACh) provocation test to evaluate microvascular dysfunction. During the ACh provocation test, we sampled blood simultaneously from the coronary sinus and aortic root to compare lactate concentrations. We quantified coronary blood flow volume using an intracoronary Doppler-tipped guidewire. We detected LGE in 34 patients (LGE-positive); 27 were LGE-negative. Coronary blood flow volume increased significantly after the ACh provocation test only in LGE-negative patients (before vs. after ACh, 47.5 ± 36.8 vs. 69.2 ± 48.0 ml/min, respectively; p = 0.004). The myocardial lactate extraction ratio (LER) significantly decreased after the ACh test in both groups (LGE-negative, p = 0.001; LGE-positive, p < 0.001), significantly more so in the LGE-positive group (p = 0.017). Multivariate logistic regression analysis showed that a post-ACh LER < 0 (indicating myocardial lactate production) was a significant predictor of LGE-positivity (odds ratio 4.54; 95 % confidence interval 1.38-14.93; p = 0.013). In the LGE-positive group, an LGE volume greater than the median significantly predicted a post-ACh LER of <0 (p = 0.042; odds ratio 6.02; 95 % confidence interval 1.07-33.86). ACh-provoked coronary vasomotor abnormality is closely correlated with myocardial fibrosis in patients with HF but without organic coronary stenosis. Coronary vasomotor abnormalities in fibrotic myocardium may worsen HF.

Comparison of endothelium-dependent and -independent vasomotor response after abluminal biodegradable polymer biolimus-eluting stent and persistent polymer everolimus-eluting stent implantation (COMPARE-IT).

BACKGROUND: Drug-eluting stents (DES) have been associated with local endothelial dysfunction in the segments proximal and distal to the stent (peristent segments) and increased thrombotic risk in long term follow-up. Little data exists on endothelial function post-implantation of new DES with biodegradable polymer. The aim of our study was to compare the local endothelial function assessed by exercise induced coronary vasomotion after implantation of a biolimus A9-eluting stent with biodegradable polymer (BES) with an everolimus-eluting stent with durable polymer (EES). METHODS: Coronary vasomotion was evaluated with quantitative coronary angiography at rest and during supine bicycle exercise in nine patients with EES and thirteen patients with BES, 16 months after stent implantation. Mean luminal diameter of the stent, peristent segments, and of a control vessel were determined at rest, during exercise, and after the administration of nitroglycerine. RESULTS: The control vessel showed exercise-induced vasodilatation in both groups (EES: +6.4±5.5%, p=0.07; BES: +7.8±10.1%, p=0.07). Vasomotion in the stented vessel segment was abolished. There was exercise-induced vasoconstriction in both groups in the segments proximal (EES: -9.6±4.5%; p=0.03; BES: -4.3±5.4%, p=0.02) and distal to the stent (EES: -3.2±9.3%; p=0.41, BES -8.6±8.0%, p<0.01). Sublingual nitroglycerin was associated with maximal vasodilatation of the peristent segments in both groups. CONCLUSION: Alike DES with durable polymer, stents with a biodegradable polymer are associated with exercise-induced paradoxical coronary vasoconstriction of the peristent segments. This data suggests that endothelial dysfunction after DES implantation is not primarily caused by the durability of the polymer coating.

Cerebral vasomotor reactivity assessment using Transcranial Doppler and MRI with apnea test

Differently from previous studies that used Transcranial Doppler (TCD) and functional MRI (fMRI) for cerebral vasomotor reactivity (CVR) assessment in patients with carotid stenosis (CS), we assessed CVR using an identical stimulus, the Breath-Holding Test (BHT). We included 15 patients with CS and 7 age-matched controls to verify whether fMRI responded differently to BHT between groups and to calculate the agreement rate between tests. For TCD, impaired CVR was defined when the mean percentage increase on middle cerebral artery velocities was ≤31% on 3 consecutive 30-s apnea intercalated by 4-min normal breathing intervals. For fMRI, the percent variation on blood oxygen level-dependent (BOLD) signal intensity in the lentiform nucleus (LN) ipsilateral to the CS (or both LNs for controls) from baseline breathing to apnea was measured. The Euclidian differences between the series of each subject and the series of controls and patients classified it into normal or impaired CVR. We found different percent variations on BOLD-signal intensities between groups (P=0.032). The agreement was good in Controls (85.7%; κ=0.69) and overall (77.3%; κ=0.54). We conclude that BHT was feasible for CVR assessment on fMRI and elicited different BOLD responses in patients and controls, with a good overall agreement between the tests.

Functional TCD: regulation of cerebral hemodynamics--cerebral autoregulation, vasomotor reactivity, and neurovascular coupling.

Three main mechanisms influence cerebral hemodynamics, with the aim of adapting the cerebral blood flow to the metabolic demand of the brain. Cerebral autoregulation ensures stable perfusion of the brain, independent of the systemic blood pressure. Vasomotor reactivity reflects the hemodynamic responses to modifications of the arterial pCO2/pH of the brain tissue. Neurovascular coupling adapts the perfusion to increased metabolic demand as a consequence of enhanced brain activity to permit reasonable functioning of cells. Different methods using transcranial Doppler sonography have been developed to characterize these mechanisms in healthy subjects and under pathologic conditions. The most established applications in clinical settings are described, and the results of specific research studies are briefly reported.

Transcranial Direct Current Stimulation and Cerebral Vasomotor Reserve: A Study in Healthy Subjects.

BACKGROUND AND PURPOSE: Cerebral vasomotor reserve (VMR) is the capability of cerebral arterioles to change their diameter in response to various stimuli, such hypercapnia. Changes of VMR due to transcranial direct current stimulation (tDCS) have been poorly studied. METHODS: Twenty-five healthy subjects underwent anodal/cathodal and sham tDCS on right primary motor area. Before and after tDCS, we assessed VMR by Transcranial Color-Coded Sonography (TCCS) calculating trought Breath Holding Index (BHI) and Heart Rate Variability (HRV), in particular after Valsalva manouver. RESULTS: A-tDCS decreased VMR and BHI (p < 0.05), whereas C-tDCS increased VMR, and BHI (p < 0.05); Sham doesn't provide statistically significant of both VMR, BHI and HRV (p > 0.05). CONCLUSIONS: Our study confirms that tDCS induces a modification of bilateral VMR with a polarity-specific effect; based on this bilateral MFV and BHI modifications, we can speculate an involvement of the SNS in the VMR regulation.

Cerebral vasomotor reactivity and risk of mortality: the Rotterdam Study.

BACKGROUND AND PURPOSE: Accumulating vascular pathology in cerebral arteries leads to impaired cerebral vasomotor reactivity. In turn, impaired cerebral vasomotor reactivity is a risk factor for stroke in clinical populations. It remains unclear whether impaired cerebral vasomotor reactivity also reflects more systemic vascular damage. We investigated whether cerebral vasomotor reactivity is associated with the risk of mortality, focusing particularly on cardiovascular mortality independent from stroke. METHODS: Between 1997 and 1999, 1695 participants from the Rotterdam Study underwent cerebral vasomotor reactivity measurements using transcranial Doppler. Follow-up was complete until January 1, 2011. We assessed the associations between cerebral vasomotor reactivity and mortality using Cox proportional hazards models, adjusting for age, sex, and blood pressure changes and subsequently for cardiovascular risk factors. We additionally censored for incident stroke. RESULTS: During 17 004 person-years, 557 participants died, of whom 181 due to a cardiovascular cause. In the fully adjusted model, the hazard ratio per SD decrease in vasomotor reactivity was 1.10 (95% confidence interval [CI], 1.01-1.19) for all-cause mortality, 1.09 (95% CI, 0.94-1.26) for cardiovascular mortality, and 1.10 (95% CI, 0.99-1.21) for noncardiovascular mortality. These associations remained unchanged after censoring for incident stroke. CONCLUSIONS: We found that lower cerebral vasomotor reactivity is associated with an increased risk of death. Incident stroke does not affect this association, suggesting that a lower cerebral vasomotor reactivity reflects a generally impaired vascular system.

Differential recovery in cardiac and vasomotor sympathetic functional markers in a patient with acute autonomic sensory and motor neuropathy.

Acute autonomic sensory and motor neuropathy (AASMN) is characterized by prominent dysautonomia with somatic sensory and motor impartment. Prominent dysautonomia is observed during the early phase of AASMN. We herein describe a case of AASMN that involved prolonged autonomic failure and disturbance of sensation despite a rapid recovery from motor weakness. The early and delayed heart-to-mediastinum ratios on (123)I-meta-iodobenzylguanidine myocardial scintigraphy were decreased and improved within seven months. However, orthostatic hypotension was prolonged. These results suggest a differential improvement in the cardiac and vasomotor sympathetic functions.

Ultrasound assessment of brachial endothelial vasomotor function in addition to carotid plaque echolucency for predicting cardiovascular events in patients with coronary artery disease.

BACKGROUND: Single assessment of either flow-mediated vasodilatation of the brachial artery (FMD) or carotid plaque echolucency provides prognostic information for both cerebrovascular and coronary events. OBJECTIVES: This study tested the hypothesis that combined assessment using carotid plaque echolucency and FMD may have an additive effect when predicting cardiovascular events in patients with coronary artery disease (CAD). METHODS: Ultrasound assessment of carotid plaque echolucency with integrated backscatter (IBS) analysis (calibrated IBS=intima-media IBS value-adventitia IBS) and FMD was performed in 547 consecutive patients with CAD. All the study patients were followed up prospectively for a period of ≤ 60 months until the occurrence of one of the following cardiovascular events: cardiac death, non-fatal myocardial infarction, unstable angina requiring coronary revascularization, or ischemic stroke. RESULTS: During a mean follow-up period of 52 ± 10 months, 69 cardiovascular events occurred. A multivariate Cox proportional hazard model after 1000 bootstrapped resampling demonstrated that calibrated IBS and FMD were significant, independent predictors of future cardiovascular events after adjustment for known risk factors (calibrated IBS, HR 0.88, 95% CI 0.83-0.93; FMD, HR 0.76, 95% CI 0.68-0.85). The c-statistics, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) analyses showed that the combination of calibrated IBS and FMD values had a greater incremental effect on the predictive value of known risk factors for cardiovascular events. CONCLUSIONS: Combined assessment of brachial endothelial function and carotid plaque echolucency is an independent predictor of cardiovascular events and improves risk prediction when added to known risks.

Effects of intermittent theta burst stimulation on cerebral blood flow and cerebral vasomotor reactivity.

OBJECTIVES: To determine whether intermittent theta burst stimulation influences cerebral hemodynamics, we investigated changes induced by intermittent theta burst stimulation on the middle cerebral artery cerebral blood flow velocity and vasomotor reactivity to carbon dioxide (CO(2)) in healthy participants. The middle cerebral artery flow velocity and vasomotor reactivity were monitored by continuous transcranial Doppler sonography. Changes in cortical excitability were tested by transcranial magnetic stimulation. METHODS: In 11 healthy participants, before and immediately after delivering intermittent theta burst stimulation, we tested cortical excitability measured by the resting motor threshold and motor evoked potential amplitude over the stimulated hemisphere and vasomotor reactivity to CO(2) bilaterally. The blood flow velocity was monitored in both middle cerebral arteries throughout the experimental session. In a separate session, we tested the effects of sham stimulation under the same experimental conditions. RESULTS: Whereas the resting motor threshold remained unchanged before and after stimulation, motor evoked potential amplitudes increased significantly (P = .04). During and after stimulation, middle cerebral artery blood flow velocities also remained bilaterally unchanged, whereas vasomotor reactivity to CO(2) increased bilaterally (P = .04). The sham stimulation left all variables unchanged. CONCLUSIONS: The expected intermittent theta burst stimulation-induced changes in cortical excitability were not accompanied by changes in cerebral blood flow velocities; however, the bilateral increased vasomotor reactivity suggests that intermittent theta burst stimulation influences the cerebral microcirculation, possibly involving subcortical structures. These findings provide useful information on hemodynamic phenomena accompanying intermittent theta burst stimulation, which should be considered in research aimed at developing this noninvasive, low-intensity stimulation technique for safe therapeutic applications.

Pulsed wave Doppler ultrasound is useful to assess vasomotor response in patients with multiple system atrophy and well correlated with tilt table study.

The study aim was to assess sympathetic vasomotor response (SVR) by using pulsed wave Doppler (PWD) ultrasound in patients with multiple system atrophy (MSA) and correlate with the tilt table study. We recruited 18 male patients and 10 healthy men as controls. The SVR of the radial artery was evaluated by PWD, using inspiratory cough as a provocative maneuver. The response to head-up tilt was studied by a tilt table with simultaneous heart rate and blood pressure recording. The hemodynamic variables were compared between groups, and were examined by correlation analysis. Regarding SVR, MSA patients exhibited a prolonged latency and less heart rate acceleration following inspiratory cough. Compared with the tilt table test, the elevation of heart rate upon SVR was positively correlated to the increase of heart rate after head-up tilt. The correlation analysis indicated that the magnitude of blood pressure drop from supine to upright was positively associated with the SVR latency but negatively correlated with the heart rate changes upon SVR. The present study demonstrated that blunted heart rate response might explain MSA's vulnerability to postural challenge. PWD may be used to predict cardiovascular response to orthostatic stress upon head-up tilt in MSA patients.