Multi-scale symbolic entropy analysis provides prognostic prediction in patients receiving extracorporeal life support

Introduction: Extracorporeal life support (ECLS) can temporarily support cardiopulmonary function, and is occasionally used in resuscitation. Multi-scale entropy (MSE) derived from heart rate variability (HRV) is a powerful tool in outcome prediction of patients with cardiovascular diseases. Multi-scale symbolic entropy analysis (MSsE), a new method derived from MSE, mitigates the effect of arrhythmia on analysis. The objective is to evaluate the prognostic value of MSsE in patients receiving ECLS. The primary outcome is death or urgent transplantation during the index admission. Methods: Fifty-seven patients receiving ECLS less than 24 hours and 23 control subjects were enrolled. Digital 24-hour Holter electrocardiograms were recorded and three MSsE parameters (slope 5, Area 6–20, Area 6–40) associated with the multiscale correlation and complexity of heart beat fluctuation were calculated. Results: Patients receiving ECLS had significantly lower value of slope 5, area 6 to 20, and area 6 to 40 than control subjects. During the follow-up period, 29 patients met primary outcome. Age, slope 5, Area 6 to 20, Area 6 to 40, acute physiology and chronic health evaluation II score, multiple organ dysfunction score (MODS), logistic organ dysfunction score (LODS), and myocardial infarction history were significantly associated with primary outcome. Slope 5 showed the greatest discriminatory power. In a net reclassification improvement model, slope 5 significantly improved the predictive power of LODS; Area 6 to 20 and Area 6 to 40 significantly improved the predictive power in MODS. In an integrated discrimination improvement model, slope 5 added significantly to the prediction power of each clinical parameter. Area 6 to 20 and Area 6 to 40 significantly improved the predictive power in sequential organ failure assessment. Conclusions: MSsE provides additional prognostic information in patients receiving ECLS. Electronic supplementary material The online version of this article (doi:10.1186/s13054-014-0548-3) contains supplementary material, which is available to authorized users

Reversible heart rhythm complexity impairment in patients with primary aldosteronism

Excess aldosterone secretion in patients with primary aldosteronism (PA) impairs their cardiovascular system. Heart rhythm complexity analysis, derived from heart rate variability (HRV), is a powerful tool to quantify the complex regulatory dynamics of human physiology. We prospectively analyzed 20 patients with aldosterone producing adenoma (APA) that underwent adrenalectomy and 25 patients with essential hypertension (EH). The heart rate data were analyzed by conventional HRV and heart rhythm complexity analysis including detrended fluctuation analysis (DFA) and multiscale entropy (MSE). We found APA patients had significantly decreased DFAα2 on DFA analysis and decreased area 1–5, area 6–15, and area 6–20 on MSE analysis (all p < 0.05). Area 1–5, area 6–15, area 6–20 in the MSE study correlated significantly with log-transformed renin activity and log-transformed aldosterone-renin ratio (all p < = 0.01). The conventional HRV parameters were comparable between PA and EH patients. After adrenalectomy, all the altered DFA and MSE parameters improved significantly (all p < 0.05). The conventional HRV parameters did not change. Our result suggested that heart rhythm complexity is impaired in APA patients and this is at least partially reversed by adrenalectomy

The Prognostic Value of Non-Linear Analysis of Heart Rate Variability in Patients with Congestive Heart Failure—A Pilot Study of Multiscale Entropy

AIMS: The influences of nonstationarity and nonlinearity on heart rate time series can be mathematically qualified or quantified by multiscale entropy (MSE). The aim of this study is to investigate the prognostic value of parameters derived from MSE in the patients with systolic heart failure. METHODS AND RESULTS: Patients with systolic heart failure were enrolled in this study. One month after clinical condition being stable, 24-hour Holter electrocardiogram was recording. MSE as well as other standard parameters of heart rate variability (HRV) and detrended fluctuation analysis (DFA) were assessed. A total of 40 heart failure patients with a mea age of 56±16 years were enrolled and followed-up for 684±441 days. There were 25 patients receiving β-blockers treatment. During follow-up period, 6 patients died or received urgent heart transplantation. The short-term exponent of DFA and the slope of MSE between scale 1 to 5 were significantly different between patients with or without β-blockers (p = 0.014 and p = 0.028). Only the area under the MSE curve for scale 6 to 20 (Area(6-20)) showed the strongest predictive power between survival (n = 34) and mortality (n = 6) groups among all the parameters. The value of Area(6-20)21.2 served as a significant predictor of mortality or heart transplant (p = 0.0014). CONCLUSION: The area under the MSE curve for scale 6 to 20 is not relevant to β-blockers and could further warrant independent risk stratification for the prognosis of CHF patients

Applying Harmonic Optical Microscopy for Spatial Alignment of Atrial Collagen Fibers

BACKGROUND: Atrial fibrosis creates a vulnerable tissue for atrial fibrillation (AF), but the spatial disarray of collagen fibers underlying atrial fibrosis is not fully elucidated. OBJECTIVE: This study hypothesizes that harmonics optical microscopy can illuminate the spatial mal-alignment of collagen fibers in AF via a layer-by-layer approach. PATIENTS AND METHODS: Atrial tissues taken from patients who underwent open-heart surgery were examined by harmonics optical microscopy. Using the two-dimensional Fourier transformation method, a spectral-energy description of image texture was constituted and its entropy was used to quantify the mal-alignment of collagen fibers. The amount of collagen fiber was derived from its area ratio to total atrial tissue in each image. Serum C-terminal pro-collagen pro-peptide (CICP), pro-matrix metalloproteinase-1 (pro-MMP-1), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were also evaluated. RESULTS: 46 patients were evaluated, including 20 with normal sinus rhythm and 26 with AF. The entropy of spectral-energy distribution of collagen alignment was significantly higher in AF than that in sinus rhythm (3.97 ± 0.33 vs. 2.80 ± 0.18, p<0.005). This difference was more significant in the permanent AF group. The amount of collagen was also significantly higher in AF patients (0.39 ± 0.13 vs. 0.18 ± 0.06, p<0.005) but serum markers of cardiac fibrosis were not significantly different between the two groups. CONCLUSIONS: Harmonics optical microscopy can quantify the spatial mal-alignment of collagen fibers in AF. The entropy of spectral-energy distribution of collagen alignment is a potential tool for research in atrial remodeling

The Correlation between Expression of Apoptosis-Related Proteins and Myocardial Functional Reserve Evaluated by Dobutamine Stress Echocardiography in Patients with Dilated Cardiomyopathy

The relation between myocardial functional changes and the apoptosis- related proteins in patients with dilated cardiomyopathy (DCM) has not yet been reported. The purpose of this study was to assess this issue through the use of dobutamine stress echocardiography. A total of 81 segments of left ventricles (from 6 patients with DCM) were collected in this study. Segments from another 5 patients who had died of noncardiac causes were used as the control. Apoptosis-related proteins (bax, bcl-2, and p53) and apoptosis were evaluated in these segments by immunocytochemical stain and terminal deoxynucleotidyl transferase-mediated DNA nick end-labeling assay. There were 26 segments with dobutamine-induced contractile reserve. There were significant differences in numbers of segments with overexpression of bcl-2 and bax in the study and control groups. However, p53 was not found in either group. The total terminal deoxynucleotidyl transferase-mediated DNA nick end-labeling-positive nuclei in explanted hearts of DCM was 0.73%. The myocardial contractile reserve was inversely associated with an overexpression of bcl-2 (P < . 01) rather than bax. in conclusion, the expression of bax and bcl-2 proteins in patients with DCM is enhanced and independent of p53. Loss of contractile reserve is associated with overexpression of bcl-2 protein in failing myocardium

Dobutamine Stress Echocardiography Compared with Exercise Thallium-201 Single-Photon Emission Computed Tomography in Detecting Coronary Artery Disease-Effect of Exercise Level on Accuracy

Dobutamine stress echocardiography (DSE) and exercise thallium-201 single - photon emission computed tomography ( SPECT) were compared for the accuracy in detecting coronary artery disease (CAD) in 51 consecutive patients. Twenty-six (group 1) of the 51 patients achieved adequate exercise end points, and 25 (group 2) did not. There were 38 patients with angiographically documented CAD. The overall sensitivity of DSE and thallium-201 SPECT in detecting CAD was 92 and 76% (p = NS), and the specificity was 77 and 77% (p = NS), respectively. The sensitivity of DSE is the same as that of SPECT in group 1 (90 vs. 90%; p = NS) and higher than that of SPECT in group 2 (94 vs. 61%; p < 0.05). In patients with CAD without a history of acute myocardial infarction or pathological Q wave on resting electrocardiogram, the sensitivity of DSE is the same as that of SPECT in group 1 (82 vs. 82%; p = NS) and also higher than that of SPECT in group 2 (90 vs. 40%; p = 0.03). The sensitivity in detecting individual coronary artery lesions with DSE and thallium-201 SPECT was not affected by the exercise level. The agreement between DSE and thallium SPECT in detecting patients with CAD was 88% in group I ( kappa = 0.69; p < 0.001) and 76% in group 2 (kappa = 0.45; p = 0.01). The agreement in detecting vascular territories with ischemia was 68% in group I (kappa = 0 .30; p < 0.01) and 75% in group 2 (kappa = 0.33; p < 0.001). The agreement in detecting vascular territories with a scar was 87% in group I (kappa = 0.55; p < 0.001) and 85% in group 2 (kappa = 0.44; p < 0.001). In conclusion, the sensitivity and specificity of DSE in detecting CAD are similar to that of thallium-201 SPECT with an exercise level ≧85% of the maximal predicted heart rate. However, in patients who cannot exercise adequately, DSE is more accurate than thallium SPECT. The agreement between DSE and thallium SPECT in detecting patients with CAD and identifying ischemia of individual vascular territories is also affected by the exercise level

Integrated Backscatter for Quantification and Risk Stratification of Blood Stagnation in Left Atrial Appendages of Patients with Rheumatic Mitral Stenosis

This study was designed to quantify the blood stagnation in left atrial appendages (LAA) of patients with rheumatic mitral stenosis, and to stratify the risk of spontaneous echo contrast (SEC) for thrombus formation. A total of 45 patients were enrolled in this study. Thirty of the 45 patients had rheumatic mitral stenosis. All the above patients were evaluated for LAA contractility by transesophageal echocardiography. Acoustic density of the stagnant blood was assessed using the integrated backscatter (IBS) mode. Multivariate linear regression analysis showed that the significant independent variables determining relative IBS in LAA were the mitral valve area (p = 0.02) and the atrial fibrillation rhythm (p = 0.0003). In patients with mitral stenosis, the IBS in LAA correlated well with the presence of thrombus (p = 0.004) and SEC (p = 0.002). Using the relative IBS in LAA with 6.8 dB as the cutoff value, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value and accuracy of SEC formation in LAA was 83, 86, 95, 60 and 83%, respectively. Using the relative IBS in LAA with 10.0 dB as the cutoff value, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value and accuracy of SEC with thrombus formation in LAA was 80, 80, 67, 89 and 80%, respectively. In conclusion, the blood stasis in LAA can be objectively quantified using IBS. Utilizing different cutoff values, the acoustic densitometry in LAA enables identification of stagnant blood which represents a risk for the development of either SEC only or SEC with thrombus formation. Copyright (C) 2000 S. Karger AG , Basel