Normal scores of deep breathing tests: beware of dysrhythmia in transthyretin amyloidosis.

BACKGROUND: The heart rate (HR) response to paced deep breathing (DB) is a common test of cardiac autonomic function, where high heart rate variability (HRV) is considered to reflect normal autonomic function. We evaluated the DB test in patients with hereditary transthyretin amyloid (ATTRm) amyloidosis, where autonomic dysregulation and atrial arrhythmias are common. METHODS: Paced DB was performed during one minute (six breaths/min) in 165 recordings in adult ATTRm amyloidosis patients with the TTR Val30Met mutation, 42 hypertrophic cardiomyopathy (HCM) patients and 211 healthy subjects. HRV was scored by traditional DB indices and by a novel regularity index, estimating the fraction of the HRV that was coherent with the breathing pattern. RESULTS: Twenty per cent of ATTRm amyloidosis patients presented with age-adjusted HRV scores within normal limits but poor regularity due to subtle atrial arrhythmias and cardiac conduction disturbances. Forty-seven per cent of ATTRm amyloidosis patients presented with HRV scores below normal limits, whereas HCM patients presented with higher HRV than ATTRm amyloidosis patients. CONCLUSIONS: Reduced HRV is common in ATTRm amyloidosis patients during DB, however, autonomic function cannot be evaluated in patients presenting with the combination of "normal" scores and low regularity, since their HR responses often reflects dysrhythmias.

Effect of resting pressure on the estimate of cerebrospinal fluid outflow conductance.

BACKGROUND: A lumbar infusion test is commonly used as a predictive test for patients with normal pressure hydrocephalus and for evaluation of cerebrospinal fluid (CSF) shunt function. Different infusion protocols can be used to estimate the outflow conductance (Cout) or its reciprocal the outflow resistance (Rout), with or without using the baseline resting pressure, Pr. Both from a basic physiological research and a clinical perspective, it is important to understand the limitations of the model on which infusion tests are based. By estimating Cout using two different analyses, with or without Pr, the limitations could be explored. The aim of this study was to compare the Cout estimates, and investigate what effect Prhad on the results. METHODS: Sixty-three patients that underwent a constant pressure infusion protocol as part of their preoperative evaluation for normal pressure hydrocephalus, were included (age 70.3 ± 10.8 years (mean ± SD)). The analysis was performed without (Cexcl Pr) and with (Cincl Pr) Pr. The estimates were compared using Bland-Altman plots and paired sample t-tests (p < 0.05 considered significant). RESULTS: Mean Cout for the 63 patients was: Cexcl Pr = 7.0 ± 4.0 (mean ± SD) µl/(s kPa) and Cincl Pr = 9.1 ± 4.3 µl/(s kPa) and Rout was 19.0 ± 9.2 and 17.7 ± 11.3 mmHg/ml/min, respectively. There was a positive correlation between methods (r = 0.79, n = 63, p < 0.01). The difference, ΔCout= -2.1 ± 2.7 µl/(s kPa) between methods was significant (p < 0.01) and ΔRout was 1.2 ± 8.8 mmHg/ml/min). The Bland-Altman plot visualized that the variation around the mean difference was similar all through the range of measured values and there was no correlation between ΔCout and Cout. CONCLUSIONS: The difference between Cout estimates, obtained from analyses with or without Pr, needs to be taken into consideration when comparing results from studies using different infusion test protocols. The study suggests variation in CSF formation rate, variation in venous pressure or a pressure dependent Cout as possible causes for the deviation from the CSF absorption model seen in some patients.

Comparison between 3 infusion methods to measure cerebrospinal fluid outflow conductance.

OBJECT: There are several infusion methods available to estimate the outflow conductance (Cout) or outflow resistance (Rout=1/Cout) of the CSF system. It has been stated that for unknown reasons, the bolus infusion method estimates a higher C(out) than steady-state infusion methods. The aim of this study was to compare different infusion methods for estimation of Cout. METHODS: The following 3 different infusion methods were used: the bolus infusion method (Cout bol); the constant flow infusion method, both static (Cout stat) and dynamic (Cout dyn) analyses; and the constant pressure infusion method (Cout cpi). Repeated investigations were performed on an experimental model with well-known characteristics, with and without physiological pressure variations (B-waves, breathing, and so on). All 3 methods were also performed in a randomized order during the same investigation in 20 patients with probable or possible idiopathic normal-pressure hydrocephalus; 6 of these patients had a shunt and 14 did not. RESULTS: Without the presence of physiological pressure variations, the concordance in the experimental model was good between all methods. When they were added, the repeatability was better for the steady-state methods and a significantly higher Cout was found with the bolus method in the region of clinically relevant Cout (p<0.05). The visual fit for the bolus infusion was dependent on subjective assessment by the operator. This experimental finding was confirmed by the clinical results, where significant differences were found in the investigations in patients without shunts between Cout of the visual bolus method and Cout stat, Cout dyn, and Cout cpi (4.58, 4.18, and 6.12 µl/[second×kPa], respectively). CONCLUSIONS: This study emphasized the necessity for standardization of Cout measurements. An experienced operator could partly compensate for difficulties in correctly estimating the pressure parameters for the bolus infusion method, but for the general user this study suggests a steady-state method for estimating Cout.

Real-time estimation of cerebrospinal fluid system parameters via oscillating pressure infusion.

Hydrocephalus is related to a disturbed cerebrospinal fluid (CSF) system. For diagnosis, lumbar infusion test are performed to estimate outflow conductance, C (out), and pressure volume index, PVI, of the CSF system. Infusion patterns and analysis methods used in current clinical practice are not optimized. Minimizing the investigation time with sufficient accuracy is of major clinical relevance. The aim of this study was to propose and experimentally evaluate a new method, the oscillating pressure infusion (OPI). The non-linear model of the CSF system was transformed into a linear time invariant system. Using an oscillating pressure pattern and linear system identification methods, C (out) and PVI with confidence intervals, were estimated in real-time. Forty-two OPI and constant pressure infusion (CPI) investigations were performed on an experimental CSF system, designed with PVI = 25.5 ml and variable C (out). The ARX model robustly estimated C (out) (mean C (out,OPI) - C (out,CPI) = 0.08 µl/(s kPa), n = 42, P = 0.68). The Box-Jenkins model proved most reliable for PVI (23.7 ± 2.0 ml, n = 42). The OPI method, with its oscillating pressure pattern and new parameter estimation methods, efficiently estimated C (out) and PVI as well as their confidence intervals in real-time. The results from this experimental study show potential for the OPI method and supports further evaluation in a clinical setting.

Experimental testing of a method for on-line identification of the cerebrospinal fluid system.

Accurate estimates of the compliance and out-flow resistance of the human cerebrospinal fluid system are important for diagnosis of a medical condition known as hydrocephalus. In this paper we present a system which provides simultaneous on-line estimates of the outflow resistance and compliance. It's performance is experimentally verified using the same apparatus used to perform actual patient diagnoses and a specially designed physical model of the human cerebrospinal fluid system.