Detection of cardiac arrhythmia patterns in ECG through H × C plane.

The aim of this study is to formulate a new methodology based upon informational tools to detect patients with cardiac arrhythmias. As it is known, sudden death is the consequence of a final arrhythmia, and here lies the relevance of the efforts aimed at the early detection of arrhythmias. The information content in the time series from an electrocardiogram (ECG) signal is conveyed in the form of a probability distribution function, to compute the permutation entropy proposed by Bandt and Pompe. This selection was made seeking its remarkable conceptual simplicity, computational speed, and robustness to noise. In this work, two well-known databases were used, one containing normal sinus rhythms and another one containing arrhythmias, both from the MIT medical databank. For different values of embedding time delay τ, normalized permutation entropy and statistical complexity measure are computed to finally represent them on the horizontal and vertical axes, respectively, which define the causal plane H×C. To improve the results obtained in previous works, a feature set composed by these two magnitudes is built to train the following supervised machine learning algorithms: random forest (RF), support vector machine (SVM), and k nearest neighbors (kNN). To evaluate the performance of each classification technique, a 10-fold cross-validation scheme repeated 10 times was implemented. Finally, to select the best model, three quality parameters were computed, namely, accuracy, the area under the receiver operative characteristic (ROC) curve (AUC), and the F1-score. The results obtained show that the best classification model to detect the ECG coming from arrhythmic patients is RF. The values of the quality parameters were at the same levels reported in the available literature using a larger data set, thus supporting this proposal that uses a very small-sized feature space to train the model later used to classify. Summarizing, the attained results show the possibility to discriminate both groups of patients, with normal sinus rhythm or arrhythmic ECG, showing a promising efficiency in the definition of new markers for the detection of cardiovascular pathologies.

Stroke Work Damping Ratio is Increased in Trained Athletes.

INTRODUCTION: Athletes training is often associated with morphological changes in the heart. In this sense, the ventricular pressure-volume (PV) relation provides a complete characterization of cardiac pump performance. Regarding the arterial system (AS), arterial wall viscosity is a source of energy dissipation, that takes place during mechanical transduction. Left ventricular stroke work (SW) constitutes the useful fraction of ventricular energy that is delivered to the AS. OBJECTIVE: Left ventricular PV-loops were evaluated in terms of AS viscous property, by means of the interaction of two SW components (Stroke Work Damping Ratio, SWDR), both in untrained and trained subjects. MATERIAL AND METHODS: Fourteen healthy individuals (seven trained) were noninvasively evaluated in terms of echocardiographic and aortic pressure measurements. RESULTS: SWDR was observed to be increased in trained subjects. CONCLUSION: SWDR was evaluated in trained individuals, being increased in comparison with the non-trained group. This effect is a consequence of a significant increase of SWD, which could be related with the viscous mechanical property of AS.

Arterial-Ventricular Coupling Impairment is Evidenced in Both Normal and Ischemic Subjects by Applying Cluster Analysis.

INTRODUCTION: Left ventricular (LV) interaction with the arterial system (arterial-ventricular coupling, AVC) is a central determinant of cardiovascular performance and cardiac energetics. Stress Echocardiography (SE) constitutes a valuable clinical tool in both diagnosis and risk stratification of patients with suspected and established coronary artery disease. Cluster Analysis (CA), an unsupervised Machine Learning technique, defines an exploratory statistical method which can be used to uncover natural groups within data. OBJECTIVE: To evaluate the capacity of CA to identify uncoupled groups with ischemic condition based on SE baseline information. MATERIAL AND METHODS: CA was applied to SE data acquired at baseline and peak exercise (PE) conditions. Obtained clusters were evaluated in terms of coupling conditions and LV wall motility alterations. RESULTS: Inter cluster significant AVC differences were obtained in terms of baseline data and changes in wall motility, confirmed by CA applied to PE data. CONCLUSION: AVC impairment was evidenced in both normal and ischemic subjects by applying CA.

Arterial-Ventricular Coupling Evaluation in Individuals with Stress-Evidenced Diastolic Dysfunction: A Pilot Study.

INTRODUCTION: Arterial-ventricular coupling (AVC) has been recognized as a key determinant of global cardiovascular performance. Diastolic dysfunction (DD) occurs when inadequate filling of the ventricles is related to an abnormal elevation of intracardiac filling pressures. In some cases, DD is evidenced during cardiac stress, provoked by exercise. OBJECTIVE: To evaluate AVC in individuals with stress evidenced DD, in relation to controls. MATERIALS AND METHODS: Stress echocardiography was applied to assess cardiac function during exercise. Arterial-ventricular coupling was evaluated, based on the assessment of left ventricular and arterial elastances. RESULTS: AVC showed a significant difference at peak exercise compared to controls, basically due to a loss of cardiac contractility. CONCLUSION: The manifestation of AVC coupling imbalance could act as a complementary parameter to support the diagnosis of DD.

A Soliton-Based Model Mimics the Arterial Pulse Propagation as Much as a Widely Used 1D Model.

INTRODUCTION: A comparison among two blood pressure pulse propagation models has made in this work. One of them is a traditional model based upon the Navier Stockes equations in one spatial dimension, the one along the direction of the arteries (from here NS1D), the other is based the concept of soliton propagation using the Korteweg De Vries equation (named KdV). METHODS: The arterial three is assumed a long successive connection of serial segments of arteries, at the inlet of the network (close up to the aorta), an acquired pulse, in vivo, wave is imposed. The computed of the peripheral blood pressure at the outlet of the final segment constitutes the output of the model (near the radial artery). RESULTS: Both models reproduced main characteristics of the measured radial wave pressure for the same input. CONCLUSION: The results show that the model KdV have many conceptual and computer benefits than the usual model NS1D that constitutes an interesting pathway for the scientific research.

Characterization of Microvascular Post Occlusive Hyperemia Using Laser Doppler Flowmetry Technique in Subjects With Cardiometabolic Disorders.

INTRODUCTION: Laser Doppler flowmetry (LDF) provides a noninvasive real-time quantification of relative changes in cutaneous perfusion. Assessment of the microvascular function can provide information on the development of various cardiometabolic disorders. In recent years, non-invasive measurements have gain attention, due to the potential complications associated to invasive procedures. OBJECTIVE: To differentiate the microvascular function between subjects with cardiometabolic disorders and healthy controls. METHODS: Evaluation through LDF during post-occlusive reactive hyperemia (PORH) in patients with or without history of cardiometabolic disorders. RESULTS: Peak values of microvascular flow during post-occlusive reactive hyperemia and both upload and recovery slopes were lesser in the pathological group. CONCLUSION: A novel approach to characterize LDF during PORH was useful to differentiate patients with cardiometabolic disorders from healthy subjects.

Beat to Beat Modulation of Arterial Pulse Wave Velocity Induced by Vascular Smooth Muscle Tone.

INTRODUCTION: The level of smooth muscle activation or `tone' (VSMT) can be defined as an intrinsic spontaneous level of vasoconstriction that may change in response to biomechanical stimuli such as flow, pressure, hormonal stimuli, neural stimuli, and drugs. Arteries can actively modify arterial pressure pulse wave velocity (PWV) by changing smooth muscle tone and diameter with little change in the mean arterial blood pressure. OBJECTIVE: To evaluate the influence of aortic VSMT in terms of beat to beat PWV variations. METHODS: Aortic pressure-diameter (P-D) relationships were invasively evaluated in five conscious animals. An `incremental' PWV was directly derived from the P-D loops, both in purely elastic conditions as well as in the presence of VSMT. RESULTS: Beat to beat PWV waveform variations showed different behavior, where mean PWV values were higher when VSMT was included in the P-D evaluation. CONCLUSION: Changes in incremental beat to beat PWV could be attributed to the influence of VSMT.

Modeling Cardiac Hemodynamic Response During Exercise in Health and Hypertrophic Cardiomyopathy.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is associated with altered hemodynamics in the left ventricular outflow tract and tissue abnormalities. Exercise testing has become an integral and powerful tool for the noninvasive evaluation of HCM and, in some patients, it could define a treatment strategy. Obiective: To model the hemodynamic alterations during exercise in healthy and HCM patients, obtained by noninvasive methods. METHODS: Cardiac output (CO), heart rate (HR), arterial blood pressure (ABP) and Total Peripheral Resistance (TPR) were assessed during exercise. The evaluation included a curve-fitting approach (sigmoidal model) that allowed a quantitative comparison of CO profiles. RESULTS: When compared to controls, patients with HCM showed reduced peak exercise cardiac output and demonstrated high peripheral resistance during exercise. Analysis of modeled it CO curves revealed a higher maximum rate of recovery in healthy individuals than in HCM patients. CONCLUSION: The application of the sigmoidal model showed to be efficient in the characterization of CO dynamics for the different studied groups.

Flow Mediated Dilation in Cirrhosis: A Pilot Study in Different Stages of the Disease.

INTRODUCTION: Cirrhosis is associated with changes in the cardiovascular system, where the circulatory dysfunction is compensated by the development of a hyperdynamic circulation. Endothelial function can be understood as the endothelium capability to release Nitric Oxide (NO) where an impairment in the normal development of this process constitutes a main step in the genesis and progression of atherosclerosis, a major cause of cardiovascular events. In recent years, non-invasive measurements have gained attention, due to the potential complications associated to invasive procedures. OBJECTIVE: To evaluate endothelial function (EF) in patients with cirrhosis, in different stages of the disease, complemented with hemodynamic measurements. METHODS: Individuals were divided in three age groups, according to the severity of their disease. EF was assessed by using the flow mediated dilation technique (FMD), jointly with noninvasive determination of cardiac output (CO), total peripheral resistance (TPR) and arterial compliance (AC). RESULTS: TPR showed a decrease in advanced severity while AC had an increase. Particularly, EF was found to be higher in CHC group, decreasing in CHB and more pronounceably in CHA. Concomitantly, an inverse behavior was observed regarding CO evolution. CONCLUSION: EF was noninvasively evaluated in cirrhosis, in terms of the progression of the disease. Hyperdynamic states in the more advanced condition were accompanied by a higher vascular reactivity, probably associated with higher peripheral NO release and increased AC.

Modeling young and adult patients with cirrhosis through a three element windkessel (WK3e).

INTRODUCTION: Measurement of hemodynamic parameters constitutes an important tool in the management of patients with cirrhosis. In recent years, non-invasive measurements have gain attention, due to the potential complications associated to invasive procedures. OBJECTIVE: To characterize the hemodynamic alterations of cirrhosis in young and adult subjects, through a three element windkessel (WK3e). METHODS: Individuals were divided in three age groups: Young Healthy group (control, CG), Young Cirrhotic Group (YCG) and Adult Cirrhotic Group (ACG). A Finapres® Nova device was used to obtain cardiac output (CO), heart rate and arterial blood pressure. Systemic arterial compliance (C), peripheral resistance (R) and characteristic impedance (Zc) were also provided. Effective arterial elastance (Ea), left ventricular work (LVW), input impedance, efficiency and model cutoff frequency (WKCF) were assessed based on the provided data. RESULTS: CO resulted to be higher in ACG than in CG and YGC. LVW, C and WKcf showed an increase, while R and Ea showed a decrease. However, this behavior was not observed in YCG. CONCLUSION: Cirrhosis was properly modeled in young and adult subjects in terms of non-invasive measurements and a WK3e.

Arterial pressure beat to beat characterization during post-occlusive reactive hyperemia.

INTRODUCTION: In recent years, peripheral arterial tonometry (PAT, a non-invasive and reproducible technique) has gained considerable interest. In this sense, arterial capacity to react to vasoactive stimulus (induced by reactive hyperemia) is known as vascular reactivity (VR). OBJECTIVE: Post ischemic beat to beat VR characterization was performed based on PAT measurements. METHODS: Systolic Blood Pressure (SBP) and Augmentation index (AIx) variations were modeled, as a response to flow stimulus. RESULTS: Obtained R2 values were around 70% for VR while, to a lesser degree, AIx fit was about 50% Conclusion: Beat to Beat VR was described in terms of SBP and AIx behavior. Further studies are needed to determine the clinical usefulness of the proposed indicators.

Evaluation of the impact of arterial wall viscosity in pressure morphology by means of a simplified 1D model.

INTRODUCTION: The interest on computational simulations of biomedical models has increased in the last years. Nevertheless, the viscous properties of vessel all are usually neglected. MATERIALS AND METHODS: A 1D model of blood flow and its interaction with the arterial wall was implemented. Non-viscous modeling and the addition of a wall-viscosity term were considered. The goodness of fit in each case was evaluated. RESULTS: Simulated radial blood pressure was generated using central blood pressure as the input of the proposed 1D tapered model. Results obtained showed an improvement as a consequence of introducing wall viscosity into the model calculations. DISCUSSION: The effect of viscoelasticity has a great significance in the implementation of computational models, since a better fit between simulated and experimental data is achieved.

Elasticity assessment of electrospun nanofibrous vascular grafts: a comparison with femoral ovine arteries.

Development of successful small-diameter vascular grafts constitutes a real challenge to biomaterial engineering. In most cases these grafts fail in-vivo due to the presence of a mechanical mismatch between the native vessel and the vascular graft. Biomechanical characterization of real native vessels provides significant information for synthetic graft development. Electrospun nanofibrous vascular grafts emerge as a potential tailor made solution to this problem. PLLA-electrospun nanofibrous tubular structures were prepared and selected as model bioresorbable grafts. An experimental setup, using gold standard and high resolution ultrasound techniques, was adapted to characterize in vitro the poly(L-lactic acid) (PLLA) electrospun structures. The grafts were subjected to near physiologic pulsated pressure conditions, following the pressure-diameter loop approach and the criteria stated in the international standard for cardiovascular implants-tubular vascular prostheses. Additionally, ovine femoral arteries were subjected to a similar evaluation. Measurements of pressure and diameter variations allowed the estimation of dynamical compliance (%C, 10(-2) mmHg) and the pressure-strain elastic modulus (E(Pε), 10(6) dyn cm(-2)) of the abovementioned vessels (grafts and arteries). Nanofibrous PLLA showed a decrease in %C (1.38±0.21, 0.93±0.13 and 0.76±0.15) concomitant to an increase in EPε (10.57±0.97, 14.31±1.47 and 17.63±2.61) corresponding to pressure ranges of 50 to 90 mmHg, 80 to 120 mmHg and 100 to 150 mmHg, respectively. Furthermore, femoral arteries exhibited a decrease in %C (8.52±1.15 and 0.79±0.20) and an increase in E(Pε) (1.66±0.30 and 15.76±4.78) corresponding to pressure ranges of 50-90 mmHg (elastin zone) and 100-130 mmHg (collagen zone). Arterial mechanics framework, extensively applied in our previous works, was successfully used to characterize PLLA vascular grafts in vitro, although its application can be directly extended to in vivo experiences, in conscious and chronically instrumented animals. The specific design and construction of the electrospun nanofibrous PLLA vascular grafts assessed in this work, showed similar mechanical properties as the ones observed in femoral arteries, at the collagen pressure range.

An hemodynamic work bench for in-vitro measurements in arterial bifurcations: experimental results and comparison with the output of a simplified CFD model.

To quantify fluid-structure interactions in arterial walls, from a biomechanical standpoint, a complete characterization of blood flow, shear stress in the interface between blood and endothelium, wall elasticity and wall stresses distribution are needed.

Are biopsy specimens predictive of HER2 status in gastric cancer patients?

BACKGROUND: Trastuzumab has been recently proposed as a treatment for patients with HER2-positive advanced/metastatic gastric cancer (GC). Since most patients have inoperable disease at diagnosis, accurate assessment of HER2 status on biopsy specimens is essential to select the patients who may benefit from therapy. AIM: The aim of this study is to establish whether HER2 status assessed on biopsy material could be reliable for treatment decisions using anti-HER2 agents. METHODS: The HER2 status was evaluated in 61 consecutive pairs of biopsy and surgical GCs samples by immunohistochemistry and chromogenic in situ hybridization. RESULTS: The overall concordance of HER2 status between biopsy and surgical specimens was 91.8 % with a predictive positive value of 71.4 % and a negative predictive value of 94.4 %. Of five discordant cases, there were three negative and two positive false biopsy results. All the false negative cases showed heterogeneous expression of HER2 protein in surgical samples. Two cases displayed overexpression of the receptors without corresponding gene amplification. CONCLUSIONS: HER2 status as evaluated on biopsy samples is a fairly good predictor of HER2 status of surgically-excised GCs. The most important influence for discordant results is tumor heterogeneity. However, HER2 overexpression, especially without coexisting gene amplification, may only be a temporary change in a tumor population. This may explain those cases with positive HER2 evaluation on biopsy material and a negative result on corresponding surgical specimen.

Association between granulomatous colitis in French Bulldogs and invasive Escherichia coli and response to fluoroquinolone antimicrobials.

BACKGROUND: French Bulldogs develop a form of granulomatous colitis (GC) with histopathological resemblance to GC of Boxer dogs (GCB). GCB is associated with mucosally invasive Escherichia coli whose eradication correlates with clinical remission. HYPOTHESIS/OBJECTIVES: To characterize the clinical and histopathological features, presence or absence of invasive colonic bacteria, and response to fluoroquinolones in French Bulldogs with GC. ANIMALS: A total of 6 French Bulldogs with a histological diagnosis of GC. METHODS: Retrospective study of medical records. Bacterial colonization was evaluated using 16S rRNA probes for eubacteria and E. coli. Biopsy specimens from 3 dogs were cultured for bacteria. Clinical response to fluoroquinolone antimicrobials was determined. RESULTS: All dogs were ≤1 year of age with hematochezia that was refractory to empirical therapy. Clinicopathologic and fecal analysis did not reveal abnormalities. Abdominal ultrasound revealed patchy thickening of the colon in 4/5 dogs and regional lymphadenopathy in 5/5. Colonoscopic abnormalities included irregularly thickened and ulcerated mucosa, hyperemia, and overt bleeding in 4/6 cases. Multifocal accumulations of PAS-positive macrophages and intramucosal E. coli were present in colonic biopsies of all 6 dogs. Administration of enrofloxacin (5/6) or marbofloxacin (1/6) at 4.4-10 mg/kg (median 10 mg/kg) PO q24h for 6-10 weeks was associated with clinical improvement within 5-14 days. All dogs remained in remission over a 3-30 month follow-up period. CONCLUSIONS: Granulomatous colitis in young French Bulldogs is associated with the presence of invasive E. coli and closely parallels GCB. Treatment with fluoroquinolone antimicrobials can induce lasting clinical remission.

Fractal dimension as an index of left ventricular ischaemia: a pilot study.

Myocardial perfusion is performed by the left and the right coronary arteries, which deliver blood to the left and right ventricles, respectively. The impairment of arterial flow supply to the cardiac muscle by disease denotes a phenomenon known as ischaemia. Previous studies have demonstrated the ability of fractal dimension (FD) value of a physiological parameter in differentiating healthy/pathological behaviours. The aim of this study consisted in quantifying the loss of ventricular thickness fractal complexity in order to determine if FD is an intrinsic marker of acute coronary ischaemia. Five mongrel dogs weighing 18.8-26.5 kg (24.4 ± 3.3, mean ± SD) were submitted to this studio. A left ventricular pressure transducer and a fluid-filled catheter for later calibration of the pressure transducer were introduced through a stab wound near the apex. Two pairs of ultrasonic microcrystals (5 MHz) for continuous wall thickness measurements were implanted at the anterior and posterior walls of the left ventricle following a previously described technique. During coronary occlusion, the ischemic wall started to thin at the very onset of relaxation (showing abnormal motility), while the normoperfused wall displayed postejective thickening. Concomitantly, posterior ventricular wall thickness and anterior wall ventricular thickness showed a significant decrease in its FD value (P <0.05). In conclusion, loss of time series fractal complexity (waveform fine structure diminution or 'unwrinkling') constitutes a marker of the presence of an ischemic process. As a result, a single scalar value is sufficient to characterize the entire behaviour of the time series. This value manifested a similar trend compared to the most well-known clinical indices of myocardial ischaemia.

Carotid-radial pulse wave velocity as a discriminator of intrinsic wall alterations during evaluation of endothelial function by flow-mediated dilatation.

UNLABELLED: Flow-mediated dilatation (FMD) is the most accepted technique for the evaluation of endothelial function. However, it has been show a great inter-subject variability limiting its clinical use. Carotid-radial pulse wave velocity (PWVcr) was proposed as an alternative tool for the evaluation of endothelial function. At the present, there is no doubt that PWVcr reduces its values in response to reactive hyperemia test (RHT) in healthy subjects. AIMS: a) to determine simultaneously the temporal profile of FMD, PWVcr and shear rate in response to RHT and b) to describe and analyze how subjects "FMD responders" or "non-responders" behave regards to PWVcr changes. METHODS: 34 Healthy young subjects were included. The PWVcr (strain gauge mechanotransducers), brachial diameter (B-Mode ultrasound and blood flow velocity (Doppler ultrasound) were measured before (baseline) the cuff was inflated and after its deflation (5 minutes). 10(th) percentiles FMD and PWVcr changes in the population were used for the definition of the subjects ("responders and non-responders"). RESULTS: Changes in PWVcr, brachial arterial diameter and shear rate were evidenced after the cuff release (p<0.05). There were differences in the PWV and FMD temporal profiles. Within "FMD responders" there were "PWV responders and non-responders". CONCLUSION: Assessing RHT-related changes in PWVcr in the context of a FMD evaluation, could be useful as a discriminator of intrinsic wall alterations giving additional information of vascular dynamics.

Arterial pressure and diameter waveforms analysis by means of wavelet transform: application to artery de-endothelization.

In this present paper, we showed that wavelet analysis (WA) has the potential for extracting specific features from measured arterial diameter and pressure waveforms. The fifth detail of the Daubechies 4 (Db4) wavelet appears to be the most appropriate level for application, in order to analyze artery waveforms and was used to characterized arterial de-endothelization (DE). Raises in smooth muscle tone induced by (DE) tended to increase arterial stiffness and therefore that WA details embed the information of the diameter and pressure pulse that contains the signature of effects of wave travel and reflection affected by arterial stiffness.