Discussion of Cuffless Blood Pressure Prediction Using Plethysmograph Based on a Longitudinal Experiment: Is the Individual Model Necessary?

Using the Plethysmograph (PPG) signal to estimate blood pressure (BP) is attractive given the convenience and possibility of continuous measurement. However, due to the personal differences and the insufficiency of data, the dilemma between the accuracy for a small dataset and the robustness as a general method remains. To this end, we scrutinized the whole pipeline from the feature selection to regression model construction based on a one-month experiment with 11 subjects. By constructing the explanatory features consisting of five general PPG waveform features that do not require the identification of dicrotic notch and diastolic peak and the heart rate, three regression models, which are partial least square, local weighted partial least square, and Gaussian Process model, were built to reflect the underlying assumption about the nature of the fitting problem. By comparing the regression models, it can be confirmed that an individual Gaussian Process model attains the best results with 5.1 mmHg and 4.6 mmHg mean absolute error for SBP and DBP and 6.2 mmHg and 5.4 mmHg standard deviation for SBP and DBP. Moreover, the results of the individual models are significantly better than the generalized model built with the data of all subjects.

Machine Learning to Understand Genetic and Clinical Factors Associated with the Pulse Waveform Dicrotic Notch

BackgroundAbsence of a dicrotic notch on finger photoplethysmography (PPG) is an easily ascertainable and inexpensive trait that has been associated with age and prevalent cardiovascular disease (CVD). However, the trait exists along a continuum, and little is known about its genetic underpinnings or prognostic value for incident CVD.MethodsIn 169,787 participants in the UK Biobank, we identified absent dicrotic notch on PPG and created a novel continuous trait reflecting notch smoothness using machine learning. Next, we determined the heritability, genetic basis, polygenic risk, and clinical relations for the binary absent notch trait and the newly derived continuous notch smoothness trait.ResultsHeritability of the continuous notch smoothness trait was 7.5%, compared with 5.6% for the binary absent notch trait. A genome wide association study of notch smoothness identified 15 significant loci, implicating genes including NT5C2 (P=1.2×10−26), IGFBP3 (P=4.8×10−18), and PHACTR1 (P=1.4×10−13), compared with 6 loci for the binary absent notch trait. Notch smoothness stratified risk of incident myocardial infarction or coronary artery disease, stroke, heart failure, and aortic stenosis. A polygenic risk score for notch smoothness was associated with incident CVD and all-cause death in UK Biobank participants without available PPG data.ConclusionWe found that a machine learning derived continuous trait reflecting dicrotic notch smoothness on PPG was heritable and associated with genes involved in vascular stiffness. Greater notch smoothness was associated with greater risk of incident CVD. Raw digital phenotyping may identify individuals at risk for disease via specific genetic pathways.

A Nano-Pharmaceutical Formula of Quercetin Protects from Cardiovascular Complications Associated with Metabolic Syndrome

Metabolic syndrome (MetS) is closely associated with the development of cardiovascular diseases. We recently developed a nano-preparation of the flavonoid quercetin (QU) in a self-nanoemulsifying drug delivery system (SNEDDS). The latter comprised a mixture composed of pumpkin seed oil, D-α-Tocopherol polyethylene glycol 1,000 succinate and polyethylene glycol. The QU SNEDDS preparations exhibited a considerably higher bioavailability compared with the standard quercetin suspension. Here, we investigated whether the quercetin loaded SNEDDS could offer better protection compared with the standard formulation against cardiovascular complications of MetS in rats. MetS was induced by high fructose, high salt and high fat diet for 12 weeks while the nano-preparation or the standard suspension of quercetin was orally administered for the last 6 weeks. Compared to little effect for the standard quercetin suspension (MQ), the treatment of MetS rats with the quercetin loaded SNEDDS (MNQ) virtually abolished the depressant effect of MetS on contractility index (control, 114 ± 4; MetS, 92 ± 3; MQ, 100 ± 2; MNQ, 114 ± 6 1/s) and rate of rise in left ventricular pressure (dP/dtmax) (control, 8,171 ± 274; MetS, 6,664 ± 135; MQ, 6,776 ± 108; MNQ, 7,498 ± 303 mmHg/s). Likewise, the prolongation by MetS of electrocardiographic markers of arrhythmogenesis (QTc, JT, and Tpeak-to-Tend intervals) and concomitant rises in dicrotic notch pressure were preferentially reversed by quercetin nano-preparation. On the other hand, the rises in the isovolumic relaxation constant (Tau, denotes diastolic dysfunction), blood pressure, pulse pressure, and difference between systolic and dicrotic pressure (SDP difference) were equally improved by the two preparations of quercetin. Additionally, no differences were noted in the ability of the two quercetin preparations in abrogating the elevated oxidative (MDA) and inflammatory (TNFα) markers in cardiac tissues of MetS rats. Histopathological, microscopical signs of necrosis, inflammatory cell infiltration, and vascular congestion in MetS hearts were more markedly inhibited by the nano-preparation, compared with the standard preparation of quercetin. In conclusion, the quercetin loaded SNEDDS is evidently more advantageous than the standard preparation of the drug in alleviating functional and histopathological manifestations of cardiac damage incited by MetS.

Digital intravascular pressure wave recording during endovascular treatment reveals abnormal shunting flow in vertebral venous fistula of the vertebral artery: illustrative case

BACKGROUND An arteriovenous fistula is an abnormal arteriovenous shunt between an artery and a vein, which often leads to venous congestion in the central nervous system. The blood flow near the fistula is different from normal artery flow. A novel method to detect the abnormal shunting flow or pressure near the fistula is needed. OBSERVATIONS A 76-year-old woman presented to the authors’ institute with progressive right upper limb weakness. Right vertebral angiography showed a fistula between the right extracranial vertebral artery (VA) and the right vertebral venous plexus at the C7 level. The patient underwent endovascular treatment for shunt flow reduction. Before the procedure, blood pressures were measured at the proximal VA, distal VA near the fistula, and just at the fistula and drainer using a microcatheter. The blood pressure waveforms were characteristically different in terms of resistance index, half-decay time, and appearance of dicrotic notch. The fistula was embolized with coils and N-butyl cyanoacrylate solution. LESSONS During endovascular treatment, the authors were able to digitally record the vascular pressure waveform from the tip of the microcatheter and succeeded in calculating several parameters that characterize the shunting flow. Furthermore, these parameters could help recognize the abnormal blood flow, allowing a safer endovascular surgery.

Self-Nanoemulsifying Drug Delivery System Loaded with Psiadia punctulata Major Metabolites for Hypertensive Emergencies: Effect on Hemodynamics and Cardiac Conductance

Vasodilators are an important class of antihypertensive agents. However, they have limited clinical use due to the reflex tachycardia associated with their use which masks most of its antihypertensive effect and raises cardiac risk. Chemical investigation of Psiadia punctulata afforded five major methoxylated flavonoids (1–5) three of which (1, 4, and 5) showed vasodilator activity. Linoleic acid-based self-nanoemulsifying drug delivery system (SNEDDS) was utilized to develop intravenous (IV) formulations that contain compounds 1, 4, or 5. The antihypertensive effect of the prepared SNEDDS formulations, loaded with each of the vasodilator compounds, was tested in the angiotensin-induced rat model of hypertension. Rats were subjected to real-time recording of blood hemodynamics and surface Electrocardiogram (ECG) while the pharmaceutical formulations were individually slowly injected in cumulative doses. Among the tested formulations, only that contains umuhengerin (1) and 5,3′-dihydroxy-6,7,4′,5′-tetramethoxyflavone (5) showed potent antihypertensive effects. Low IV doses, from the prepared SNEDDS, containing either compound 1 or 5 showed a marked reduction in the elevated systolic blood pressure by 10 mmHg at 12 μg/kg and by more than 20 mmHg at 36 μg/kg. The developed SNEDDS formulation containing either compound 1 or 5 significantly reduced the elevated diastolic, pulse pressure, dicrotic notch pressure, and the systolic–dicrotic notch pressure difference. Moreover, both formulations decreased the ejection duration and increased the non-ejection duration while they did not affect the time to peak. Both formulations did not affect the AV conduction as appear from the lack of effect on p duration and PR intervals. Similarly, they did not affect the ventricular repolarization as no effect on QTc or JT interval. Both formulations decreased the R wave amplitude but increased the T wave amplitude. In conclusion, the careful selection of linoleic acid for the development of SNEDDS formulation rescues the vasodilating effect of P. punctulata compounds from being masked by the reflex tachycardia that is commonly associated with the decrease in peripheral resistance by most vasodilators. The prepared SNEDDS formulation could be suggested as an effective medication in the treatment of hypertensive emergencies, after clinical evaluation.

Influence of digital filtering parameters on the pulse waveform in reflectance photoplethysmography

Photoplethysmography (PPG) is an optical method for recording pulse wave (PW) propagating in the tissue microvasculature. As a rule, filters with infinite impulse response (Butterworth, Bessel, etc.) often used in PPG signal processing introduce distortions in the PW signal. At the same time, the filtering parameters for a more accurate reproduction of PW have not yet been substantiated. The aim of this work is to study the influence of digital filtering parameters, such as bandwidth and filter order, on the pulse waveform. In the study, a digital bandpass Butterworth filter was used. The lower cutoff frequency of the filter varied from 0.1 to 1 Hz, the upper cutoff frequency varied from 2 to 10 Hz and the filter order – from 2nd to 6th. It was found that an increase in the lower cutoff frequency of the bandpass filtering leads to a decrease in the amplitude of the reflected diastolic wave and distortion of the front of the direct systolic wave. A decrease in the upper cutoff frequency leads to damping of the dicrotic notch and a phase shift of the PW. Increasing the filter order decreases the reflected wave amplitude. The minimal distortions of the PPG signal were observed at the lower cutoff frequency of 0.1 Hz, the upper one at 10 Hz and the filter order equal to 2. Thus, these parameters of a bandpass filtering can be recommended for processing PPG signals for a more accurate morphological analysis of PW. The obtained results make it possible to create devices for PW analysis with substantiated medical and technical requirements for filtration parameters.