João Freitas

Clinical improvement in patients with orthostatic intolerance after treatment with bisoprolol and fludrocortisone

Orthostatic intolerance is the development of disabling symptoms upon assuming an upright posture that are relieved partially by resuming the supine position. Postural tachycardia syndrome (POTS) is an orthostatic intolerance syndrome characterized by palpitations because of excessive orthostatic sinus tachycardia, lightheadedness, tremor, and near-syncope. Patients usually undergo extensive medical, cardiac, endocrine, neurologic, and psychiatric evaluation, which usually fails to identify a specific abnormality. The authors investigated the autonomic and hemodynamic profile of patients with POTS and the effectiveness of bisoprolol and fludrocortisone. The authors evaluated 11 female patients with POTS before and after medical treatment with a cardioselective bisoprolol β-blocker or fludrocortisone, or both, and 11 age-matched control patients. Variability of heart rate and systolic blood pressure was assessed by fast Fourier transform, and spontaneous baroreceptor gain was assessed by use of the temporal sequences slope and α index. Modelflow was used to quantify hemodynamics. Symptoms in all patients improved greatly after medication. The autonomic and hemodynamic impairment observed in patients with POTS, particularly after orthostatic stress, is treated effectively with bisoprolol or fludrocortisone or both. These results need further confirmation in a controlled double-blind study. Proper medical treatment improves dramatically the clinical and autonomic-hemodynamic disturbances observed in patients with POTS. The data support the hypothesis that POTS is the result of a hyperadrenergic activation or hypovolemia during orthostasis.

Circadian heart rate variability rhythm in shift workers

The objective of this study was to assess the influence of day-night cycle and sleep-awake period on the circadian pattern of heart rate variability (HRV). Twelve male oil refinery security shift workers, aged 39 +/- 7 years, were studied with 24-hour Holter monitor recordings during morning and night work periods. Hourly HRV parameters in the time and frequency domains were evaluated. For both shifts, all HRV parameters during awake or work periods were found not to be statistically different. In both day and night work shifts, the very low frequency and high-frequency components of HRV and the proportion of differences in successive R-R intervals greater than 50 ms increased during the sleep period, while the low frequency/high frequency ratio decreased. The low-frequency component in absolute units and the SD of the R-R interval did not show any variation in either shifts for the different periods. These results suggest that the circadian pattern of HRV seems to be predominantly related to sleep (supine) and wakefulness (standing) and remains independent of night-day cycle.

Interplay of cerebral autoregulation and neurovascular coupling evaluated by functional TCD in different orthostatic conditions

BackgroundAdequate cerebral blood flow (CBF) is mainly governed by neurovascular coupling (NC) which adapts local CBF to underlying cortical activity, and cerebral autoregulation (CA) that tends to maintain constant CBF despite changes in arterial blood pressure (BP). Since it was suggested that resistance vessels play an important role in both mechanisms, we investigated their regulative interplay by performing a functional transcranial Doppler (f-TCD) test under different orthostatic conditions.MethodsFifteen healthy volunteers performed a visual reading test stimulation task after stabilized in sitting, supine and upright position on a tilt table. Simultaneously, BP and heart rate (HR) were recorded by a photoplethysmographic method and CBF velocity was measured with TCD in left posterior cerebral artery, and, as a reference, also in right middle cerebral artery. Evoked flow velocity (FV) responses were evaluated by a control system approach for systolic and diastolic data. Parameters studied were baseline FV with eyes closed, stable FV under stimulation (gain), oscillatory feature (natural frequency) and damping (attenuation) of the control system model, rate time, and also systolic and diastolic BP and HR. ANOVA test was used for comparing the values of variables in different postural settings, inferring statistical significance at a p < 0,05 level.ResultsAlthough there was a significant variation on the different orthostatic conditions in systolic (p = 0,027) and diastolic (p = 0,001) BP and HR (p = 0,0001), there was no significant change in the basal or evoked CBF velocities.ConclusionsAn intact CA compensates the different orthostatic conditions completely thus allowing an independent regulation of NC according to the metabolic needs of cortical stimulation.

B-Type Natriuretic Peptide Is Related to Left Ventricular Mass in Hypertensive Patients but Not in Athletes

A positive correlation has been previously documented between B-type natriuretic peptide (BNP) levels and left ventricular mass index (LVMI) in hypertensive patients. We evaluated 8 cycling athletes, 8 healthy age-matched controls; 17 hypertensive patients and 7 age-matched controls. LVMI was significantly higher in athletes and hypertensive patients than in their controls. Plasma levels of BNP in hypertensive patients were significantly higher than in athletes and their age-matched controls. No significant difference was found between athletes and their controls. Cycling athletes had significantly larger LVMI than hypertensive patients and controls, without elevated BNP levels. These results suggest that BNP levels are elevated in patients with increased LVM due to hypertension but not in physiologically increased LVM. Whether elevated BNP levels in athletes is a sign of structural heart disease merits further investigation.

Autonomic dysfunction affects cerebral neurovascular coupling

ObjectiveAutonomic failure (AF) affects the peripheral vascular system, but little is known about its influence on cerebrovascular regulation. Patients with familial amyloidotic polyneuropathy (FAP) were studied as a model for AF.MethodsTen mild (FAPm), 10 severe (FAPs) autonomic dysfunction FAP patients, and 15 healthy controls were monitored in supine and sitting positions for arterial blood pressure (ABP) and heart rate (HR) with arterial volume clamping, and for blood flow velocity (BFV) in posterior (PCA) and contralateral middle cerebral arteries (MCA) with transcranial Doppler. Analysis included resting BFV, cerebrovascular resistance parameters (cerebrovascular resistance index, CVRi; resistance area product, RAP; and critical closing pressure, CrCP), and neurovascular coupling through visually evoked BFV responses in PCA (gain, rate time, attenuation, and natural frequency).ResultsIn non-stimulation conditions, in each position, there were no significant differences between the groups, regarding HR, BP, resting BFV, and vascular resistance parameters. Sitting ABP was higher than in supine in the three groups, although only significantly in controls. Mean BFV was lower in sitting in all the groups, lacking statistical significance only in FAPs PCA. CVRi and CrCP increased with sitting in all the groups, while RAP increased in controls but decreased in FAPm and FAPs. In visual stimulation conditions, FAPs comparing to controls had a significant decrease of natural frequency, in supine and sitting, and of rate time and gain in sitting position.InterpretationThese results demonstrate that cerebrovascular regulation is affected in FAP subjects with AF, and that it worsens with orthostasis.

Heart rate variability in brain death

The sensitivity and specificity of heart rate variability (HRV) in the corroboration of brain death diagnosis in patients with acute traumatic intracranial lesions was evaluated in 20 patients with clinical criteria of brain death, nine patients in deep coma (Glasgow scale <7) and 18 normal controls, all age matched. The electrocardiogram was sampled at 650 Hz and several parameters of HRV were calculated, in both time and frequency domains. The HRV parameters were significantly lower in the brain death group compared with the deep coma group. Linear discriminant analysis between brain death and deep coma patients was performed on a data set made of nine randomly selected patients with clinical criteria of brain death and nine patients in deep coma. Cross-validation was performed on the remaining 11 patients with clinical criteria of brain death. All patients in the data set were correctly classified (sensitivity and specificity of 100%). All patients in the cross-validation set were correctly classified (sensitivity of 100%). Further studies are necessary to evaluate the specificity of the method in the independent set of deep coma patients and in the follow-up of comatose and vegetative patients to identify irreversibility of HRV. Nevertheless, these results suggest that HRV analysis constitutes a fully sensitive and specific method for assessing brain death in potential organ donors with acute traumatic lesions of the brain. This fast, quantitative and bedside method seems very promising for the early confirmation of brain death, which is an important factor for the success of transplantation procedures and could have a high predictive value of brain death in comatose patients with brain injuries without fully diagnostic criteria.

Autonomic dysfunction affects dynamic cerebral autoregulation during Valsalva maneuver: comparison between healthy and autonomic dysfunction subjects

The role of autonomic nervous system (ANS) in adapting cerebral blood flow (CBF) to arterial blood pressure (ABP) fluctuations [cerebral autoregulation (CA)] is still controversial. We aimed to study the repercussion of autonomic failure (AF) on dynamic CA during the Valsalva maneuver (VM). Eight AF subjects with familial amyloidotic polineuropahty (FAP) were compared with eight healthy controls. ABP and CBF velocity (CBFV) were measured continuously with Finapres and transcranial Doppler, respectively. Cerebrovascular response was evaluated by cerebrovascular resistance index (CVRi), critical closing pressure (CrCP), and resistance-area product (RAP) changes. Dynamic CA was derived from continuous estimates of autoregulatory index (ARI) [ARI(t)]. During phase II of VM, FAP subjects showed a more pronounced decrease in normalized CBFV (78 ± 19 and 111 ± 16%; P = 0.002), ABP (78 ± 19 and 124 ± 12%; P = 0.0003), and RAP (67 ± 17 and 89 ± 17%; P = 0.019) compared with controls. CrCP and CVRi increased similarly in both groups during strain. ARI(t) showed a biphasic variation in controls with initial increase followed by a decrease during phase II but in FAP this response was blunted (5.4 ± 3.0 and 2.0 ± 2.9; P = 0.033). Our data suggest that dynamic cerebral autoregulatory response is a time-varying phenomena during VM and that it is disturbed by autonomic dysfunction. This study also emphasizes the fact that RAP + CrCP model allowed additional insights into understanding of cerebral hemodynamics, showing a higher vasodilatory response expressed by RAP in AF and an equal CrCP response in both groups during the increased intracranial and intrathoracic pressure, while classical CVRi paradoxically suggests a cerebral vasoconstriction.

Deep brain stimulation does not change neurovascular coupling in non-motor visual cortex: An autonomic and visual evoked blood flow velocity response study

BACKGROUND AND PURPOSE In Parkinsons disease (PD) subthalamic nucleus deep brain stimulation (STN-DBS) improves motor function. Also an effect on the neurovascular coupling in motor cortex was reported due to a parallel activation of a subthalamic vasodilator area (SVA). To address this issue further we analysed neurovascular coupling in a non-motor area. METHODS Twenty PD patients selected for bilateral STN-DBS were investigated with functional transcranial Doppler (f-TCD) before and after surgery. Hemodynamic responses to visual stimulation were registered in left posterior cerebral artery (PCA) and analysed with a control-system approach (parameters gain, rate time, attenuation and natural frequency). To exclude autonomic effects of STN-DBS, we also addressed spectrum analysis of heart rate and of systolic arterial blood pressure variability, and baroreceptor gain. Findings in the PD group were compared with healthy age-matched controls. RESULTS PD patients showed no neurovascular coupling changes in PCA territory, compared to controls, and STN-DBS changed neither blood flow regulatory parameters nor autonomic function. CONCLUSIONS Improvement of vasoregulation in some motor cortical areas after STN-DBS might be related to an improved neuronal functional rather than indicating an effect on the neurovascular coupling or autonomic function.

Heart rate variability in 24-hour holter recordings: Comparative study between short- and long-term time- and frequency-domain analyses

Mean hourly parameters obtained from all beats (long series) were compared with those obtained from a sample of 512 beats extracted each hour (short series) in nine presumably normal subjects. For both the short and long series, the spectral components, very low frequency, (VLF), low frequency (LF), and high frequency (HF), and time-domain indices (such as the Ewing statistic [PNN50] and RR standard deviation [SD-RR]), have been estimated. The spectral components LF and HF, estimated from the short and long series, were not significantly different, whereas significant differences were found between VLF, SD--RR, and PNN50. In both the short and long series, a strong correlation was found between LF and SD-RR and between HF and PNN50. The results suggest that, over a period of 24 hours, hourly LF and HF spectral components can be obtained using a single series of 512 beats every hour, with a great advantage over the evaluation of the mean hourly parameters. This method would be particularly useful in the study of circadian heart rate spectral analysis in Holter recordings with multiple artifacts or ectopic beats, and in general, when analysis of the entire 24-hour series is not feasible.

High altitude-related neurocardiogenic syncope

This report presents a well-documented link between vasodepressor syncope, a marked increase of LF/HF ratio response to orthostasis (sympathetic dominance), and the efficacy of beta blockers in preventing orthostatic symptoms and absence of tilt-induced syncope, with normalization of the LF/HF ratio response.