Noninvasive Venous Waveform Analysis Correlates With Pulmonary Capillary Wedge Pressure and Predicts 30-Day Admission in Patients With Heart Failure Undergoing Right Heart Catheterization.

BACKGROUND: Heart failure is the leading cause of hospitalization in the elderly and readmission is common. Clinical indicators of congestion may not precede acute congestion with enough time to prevent hospital admission for heart failure. Thus, there is a large and unmet need for accurate, noninvasive assessment of congestion. Noninvasive venous waveform analysis in heart failure (NIVAHF) is a novel, noninvasive technology that monitors intravascular volume status and hemodynamic congestion. The objective of this study was to determine the correlation of NIVAHF with pulmonary capillary wedge pressure (PCWP) and the ability of NIVAHF to predict 30-day admission after right heart catheterization. METHODS AND RESULTS: The prototype NIVAHF device was compared with the PCWP in 106 patients undergoing right heart catheterization. The NIVAHF algorithm was developed and trained to estimate the PCWP. NIVA scores and central hemodynamic parameters (PCWP, pulmonary artery diastolic pressure, and cardiac output) were evaluated in 84 patients undergoing outpatient right heart catheterization. Receiver operating characteristic curves were used to determine whether a NIVA score predicted 30-day hospital admission. The NIVA score demonstrated a positive correlation with PCWP (r = 0.92, n = 106, P < .0001). The NIVA score at the time of hospital discharge predicted 30-day admission with an AUC of 0.84, a NIVA score of more than 18 predicted admission with a sensitivity of 91% and specificity of 56%. Residual analysis suggested that no single patient demographic confounded the predictive accuracy of the NIVA score. CONCLUSIONS: The NIVAHF score is a noninvasive monitoring technology that is designed to provide an estimate of PCWP. A NIVA score of more than 18 indicated an increased risk for 30-day hospital admission. This noninvasive measurement has the potential for guiding decongestive therapy and the prevention of hospital admission in patients with heart failure.

Heart rate variability during sleep in children with autism spectrum disorder.

PURPOSE: Autonomic dysfunction has been reported in autism spectrum disorders (ASD). Less is known about autonomic function during sleep in ASD. The objective of this study is to provide insight into the autonomic cardiovascular control during different sleep stages in ASD. We hypothesized that patients with ASD have lower vagal and higher sympathetic modulation with elevated heart rate, as compared to typical developing children (TD). METHODS: We studied 21 children with ASD and 23 TD children during overnight polysomnography. Heart rate and spectral parameters were calculated for each vigilance stage during sleep. Data from the first four sleep cycles were used to avoid possible effects of different individual sleep lengths and sleep cycle structures. Linear regression models were applied to study the effects of age and diagnosis (ASD and TD). RESULTS: In both groups, HR decreased during non-REM sleep and increased during REM sleep. However, HR was significantly higher in stages N2, N3 and REM sleep in the ASD group. Children with ASD showed less high frequency (HF) modulation during N3 and REM sleep. LF/HF ratio was higher during REM. Heart rate decreases with age at the same level in ASD and in TD. We found an age effect in LF in REM different in ASD and TD. CONCLUSION: Our findings suggest possible deficits in vagal influence to the heart during sleep, especially during REM sleep. Children with ASD may have higher sympathetic dominance during sleep but rather due to decreased vagal influence.

Efficacy of Servo-Controlled Splanchnic Venous Compression in the Treatment of Orthostatic Hypotension: A Randomized Comparison With Midodrine.

UNLABELLED: Splanchnic venous pooling is a major hemodynamic determinant of orthostatic hypotension, but is not specifically targeted by pressor agents, the mainstay of treatment. We developed an automated inflatable abdominal binder that provides sustained servo-controlled venous compression (40 mm Hg) and can be activated only on standing. We tested the efficacy of this device against placebo and compared it to midodrine in 19 autonomic failure patients randomized to receive either placebo, midodrine (2.5-10 mg), or placebo combined with binder on separate days in a single-blind, crossover study. Systolic blood pressure (SBP) was measured seated and standing before and 1-hour post medication; the binder was inflated immediately before standing. Only midodrine increased seated SBP (31±5 versus 9±4 placebo and 7±5 binder, P=0.003), whereas orthostatic tolerance (defined as area under the curve of upright SBP [AUCSBP]) improved similarly with binder and midodrine (AUCSBP, 195±35 and 197±41 versus 19±38 mm Hg×minute for placebo; P=0.003). Orthostatic symptom burden decreased with the binder (from 21.9±3.6 to 16.3±3.1, P=0.032) and midodrine (from 25.6±3.4 to 14.2±3.3, P<0.001), but not with placebo (from 19.6±3.5 to 20.1±3.3, P=0.756). We also compared the combination of midodrine and binder with midodrine alone. The combination produced a greater increase in orthostatic tolerance (AUCSBP, 326±65 versus 140±53 mm Hg×minute for midodrine alone; P=0.028, n=21) and decreased orthostatic symptoms (from 21.8±3.2 to 12.9±2.9, P<0.001). In conclusion, servo-controlled abdominal venous compression with an automated inflatable binder is as effective as midodrine, the standard of care, in the management of orthostatic hypotension. Combining both therapies produces greater improvement in orthostatic tolerance. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00223691.

Smart Multi-Frequency Bioelectrical Impedance Spectrometer for BIA and BIVA Applications.

Bioelectrical impedance analysis (BIA) is a noninvasive and commonly used method for the assessment of body composition including body water. We designed a small, portable and wireless multi-frequency impedance spectrometer based on the 12 bit impedance network analyzer AD5933 and a precision wide-band constant current source for tetrapolar whole body impedance measurements. The impedance spectrometer communicates via Bluetooth with mobile devices (smart phone or tablet computer) that provide user interface for patient management and data visualization. The export of patient measurement results into a clinical research database facilitates the aggregation of bioelectrical impedance analysis and biolectrical impedance vector analysis (BIVA) data across multiple subjects and/or studies. The performance of the spectrometer was evaluated using a passive tissue equivalent circuit model as well as a comparison of body composition changes assessed with bioelectrical impedance and dual-energy X-ray absorptiometry (DXA) in healthy volunteers. Our results show an absolute error of 1% for resistance and 5% for reactance measurements in the frequency range of 3 kHz to 150 kHz. A linear regression of BIA and DXA fat mass estimations showed a strong correlation (r(2)=0.985) between measures with a maximum absolute error of 6.5%. The simplicity of BIA measurements, a cost effective design and the simple visual representation of impedance data enables patients to compare and determine body composition during the time course of a specific treatment plan in a clinical or home environment.

Ratiometric imaging of calcium during ischemia-reperfusion injury in isolated mouse hearts using Fura-2.

BACKGROUND: We present an easily implementable method for measuring Fura-2 fluorescence from isolated mouse hearts using a commercially available switching light source and CCD camera. After calibration, it provides a good estimate of intracellular [Ca2+] with both high spatial and temporal resolutions, permitting study of changes in dispersion of diastolic [Ca2+], Ca2+ transient dynamics, and conduction velocities in mouse hearts. In a proof-of-principle study, we imaged isolated Langendorff-perfused mouse hearts with reversible regional myocardial infarctions. METHODS: Isolated mouse hearts were perfused in the Landendorff-mode and loaded with Fura-2. Hearts were then paced rapidly and subjected to 15 minutes of regional ischemia by ligation of the left anterior descending coronary artery, following which the ligation was removed to allow reperfusion for 15 minutes. Fura-2 fluorescence was recorded at regular intervals using a high-speed CCD camera. The two wavelengths of excitation light were interleaved at a rate of 1 KHz with a computer controlled switching light source to illuminate the heart. RESULTS: Fura-2 produced consistent Ca2+ transients from different hearts. Ligating the coronary artery rapidly generated a well defined region with a dramatic rise in diastolic Ca2+ without a significant change in transient amplitude; Ca2+ handling normalized during reperfusion. Conduction velocity was reduced by around 50% during ischemia, and did not recover significantly when monitored for 15 minutes following reperfusion. CONCLUSIONS: Our method of imaging Fura-2 from isolated whole hearts is capable of detecting pathological changes in intracellular Ca2+ levels in cardiac tissue. The persistent change in the conduction velocities indicates that changes to tissue connectivity rather than altered intracellular Ca2+ handling may be underlying the electrical instabilities commonly seen in patients following a myocardial infarction.

Continuous-waveform constant-current isolated physiological stimulator.

We have developed an isolated continuous-waveform constant-current physiological stimulator that is powered and controlled by universal serial bus (USB) interface. The stimulator is composed of a custom printed circuit board (PCB), 16-MHz MSP430F2618 microcontroller with two integrated 12-bit digital to analog converters (DAC0, DAC1), high-speed H-Bridge, voltage-controlled current source (VCCS), isolated USB communication and power circuitry, two isolated transistor-transistor logic (TTL) inputs, and a serial 16 × 2 character liquid crystal display. The stimulators are designed to produce current stimuli in the range of ±15 mA indefinitely using a 20V source and to be used in ex vivo cardiac experiments, but they are suitable for use in a wide variety of research or student experiments that require precision control of continuous waveforms or synchronization with external events. The device was designed with customization in mind and has features that allow it to be integrated into current and future experimental setups. Dual TTL inputs allow replacement by two or more traditional stimulators in common experimental configurations. The MSP430 software is written in C++ and compiled with IAR Embedded Workbench 5.20.2. A control program written in C++ runs on a Windows personal computer and has a graphical user interface that allows the user to control all aspects of the device.