AimsThe 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 ResultsPatients 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 (Area6–20) showed the strongest predictive power between survival (n = 34) and mortality (n = 6) groups among all the parameters. The value of Area6–20 21.2 served as a significant predictor of mortality or heart transplant (p = 0.0014).ConclusionThe 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.

In ICU-admitted patients with acute stroke, early assessment of the complexity of HRV by MSE can help in predicting outcomes in patients without AF.

Increases in collagen content in the myocardium of APA patients may be reversed by adrenalectomy.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular atherosclerosis independent of classical risk factors. This study investigated the influence of NAFLD on autonomic changes, which is currently unknown.MethodsSubjects without an overt history of cardiovascular disease were enrolled during health checkups. The subjects diagnosed for NAFLD using ultrasonography underwent 5-min heart rate variability (HRV) measurements that was analyzed using the following indices: (1) the time domain with the standard deviation of N-N (SDNN) intervals and root mean square of successive differences between adjacent N-N intervals (rMSSD); (2) the frequency domain with low frequency (LF) and high frequency (HF) components; and (3) symbolic dynamics analysis. Routine blood biochemistry data and serum leptin levels were analyzed. Homeostasis model assessment of insulin resistance (HOMA-IR) was measured.ResultsOf the 497 subjects (mean age, 46.2 years), 176 (35.4%) had NAFLD. The HRV indices (Ln SDNN, Ln rMSSD, Ln LF, and Ln HF) were significantly decreased in the NAFLD group (3.51 vs 3.62 ms, 3.06 vs 3.22 ms, 5.26 vs 5.49 ms2, 4.49 vs 5.21 ms2, respectively, all P<0.05). Ln SDNN was significantly lower in the NAFLD group after adjustment for age, sex, hypertension, dyslipidemia, metabolic syndrome, body mass index, smoking, estimated glomerular filtration rate, HOMA-IR, and leptin (P<0.05). In the symbolic dynamic analysis, 0 V percentage was significantly higher in the NAFLD group (33.8% vs 28.7%, P = 0.001) and significantly correlated with linear HRV indices (Ln SDNN, Ln rMSSD, and Ln HF).ConclusionsNAFLD is associated with decreased Ln SDNN and increased 0 V percentage. The former association was independent of conventional cardiovascular risk factors and serum biomarkers (insulin resistance and leptin). Further risk stratification of autonomic dysfunction with falls or cardiovascular diseases by these HRV parameters is required in patients with NAFLD.

BackgroundTelehealth based on advanced information technology is an emerging health care strategy for managing chronic diseases. However, the cost-effectiveness and clinical effect of synchronous telehealth services in older patients with cardiovascular diseases has not yet been studied. Since 2009, the Telehealth Center at the National Taiwan University Hospital has provided a range of telehealth services (led by a cardiologist and staffed by cardiovascular nursing specialists) for cardiovascular disease patients including (1) instant transmission of blood pressure, pulse rate, electrocardiography, oximetry, and glucometry for analysis, (2) mutual telephone communication and health promotion, and (3) continuous analytical and decision-making support.ObjectiveTo evaluate the impact of a synchronous telehealth service on older patients with cardiovascular diseases.MethodsBetween November 2009 and April 2010, patients with cardiovascular disease who received telehealth services at the National Taiwan University Hospital were recruited. We collected data on hospital visits and health expenditures for the 6-month period before and the 6-month period after the opening of the Telehealth Center to assess the clinical impact and cost-effectiveness of telehealth services on cardiovascular patients.ResultsA total of 141 consecutive cardiovascular disease patients were recruited, including 93 aged ≥65 years (senior group) and 48 aged <65 years (nonsenior group). The telehealth intervention significantly reduced the all-cause admission rate per month per person in the nonsenior group (pretelehealth: median 0.09, IQR 0-0.14; posttelehealth: median 0, IQR 0-0; P=.002) and the duration (days per month per person) of all-cause hospital stay (pretelehealth: median 0.70, IQR 0-1.96; posttelehealth: median 0, IQR 0-0; P<.001) with increased all-cause outpatient visits per month per person (pretelehealth: median 0.77, IQR 0.20-1.64; posttelehealth: mean 1.60, IQR 1.06-2.57; P=.002). In the senior group, the telehealth intervention also significantly reduced the all-cause admission rate per month per person (pretelehealth: median 0.10, IQR 0-0.18; posttelehealth: median 0, IQR 0-0; P<.001) and the duration (days per month per person) of all-cause hospital stay (pretelehealth: median 0.59, IQR 0-2.24; posttelehealth: median 0, IQR 0-0; P<.001) with increased all-cause outpatient visits per month per person (pretelehealth: median 1.40, IQR 0.52-2.63; posttelehealth: median 1.76, IQR 1.12-2.75; P=.02). In addition, telehealth intervention reduced the inpatient cost in the nonsenior group from $814.93 (SD 1000.40) to US $217.39 (SD 771.01, P=.001) and the total cost per month from US $954.78 (SD 998.70) to US $485.06 (SD 952.47, P<.001). In the senior group, the inpatient cost per month was reduced from US $768.27 (SD 1148.20) to US $301.14 (SD 926.92, P<.001) and the total cost per month from US $928.20 (SD 1194.11) to US $494.87 (SD 1047.08, P<.001).ConclusionsSynchronous telehealth intervention may reduce costs, decrease all-cause adm...

To develop the first heart-specific tetracycline (Tet)-On system in zebrafish, we constructed plasmids in which the cardiac myosin light chain 2 promoter of zebrafish was used to drive the reverse Tet-controlled transactivator (rtTA) and the green fluorescent protein (GFP) reporter gene was preceded by an rtTAresponsive element. In the zebrafish fibroblast cell-line, rtTA-M2, one of rtTA's derivatives, demonstrated the highest increase in luciferase activity upon doxycycline (Dox) induction. We then generated two germ lines of transgenic zebrafish: line T03 was derived from microinjection of a plasmid containing rtTA-M2 and a plasmid containing a responsive reporter gene, whereas line T21 was derived from microinjection of a single dual plasmid. Results showed that line T21 was superior to line T03 in terms of greater GFP intensity after induction and with of minimal leakiness before induction. The photographic images of induced GFP in the heart of F2 larvae showed that the fluorescent level of GFP was dose-responsive. The level of GFP expressed in the F3 3 days postfertilization larvae that were treated with Dox for 1 hr decreased gradually after the withdrawal of the inducer; and the fluorescent signal disappeared after 5 days. The GFP induction and reduction were also tightly controlled by Dox in the F3 adult fish from line T21. This Tet-On system developed in zebrafish shows much promise for the study of the gene function in a specific tissue at the later developmental stage. Developmental Dynamics 233:1294 -1303, 2005.

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.

BackgroundTelehealth programs are a growing field in the care of patients. The evolution of information technology has resulted in telehealth becoming a fourth-generation synchronous program. However, long-term outcomes and cost-effectiveness analysis of fourth-generation telehealth programs have not been reported in patients with chronic cardiovascular diseases.ObjectiveWe conducted this study to assess the clinical outcomes and cost-effectiveness of a fourth-generation synchronous telehealth program for patients with chronic cardiovascular diseases.MethodsWe retrospectively analyzed 575 patients who had joined a telehealth program and compared them with 1178 patients matched for sex, age, and Charlson comorbidity index. The program included: (1) instant transmission of biometric data, (2) daily telephone interview, and (3) continuous decision-making support. Data on hospitalization, emergency department (ED) visits, and medical costs were collected from the hospital’s database and were adjusted to the follow-up months.ResultsThe mean age was 64.5 years (SD 16.0). The mean number of monthly ED visits (mean 0.06 SD 0.13 vs mean 0.09 SD 0.23, P<.001), hospitalizations (mean 0.05 SD 0.12 vs mean 0.11 SD 0.21, P<.001), length of hospitalization (mean 0.77 days SD 2.78 vs mean 1.4 SD 3.6, P<.001), and intensive care unit admissions (mean 0.01 SD 0.07 vs mean 0.036 SD 0.14, P<.001) were lower in the telehealth group. The monthly mean costs of ED visits (mean US$20.90 SD 66.60 vs mean US$37.30 SD 126.20, P<.001), hospitalizations (mean US$386.30 SD 1424.30 vs mean US$878.20 SD 2697.20, P<.001), and all medical costs (mean US$587.60 SD 1497.80 vs mean US$1163.60 SD 3036.60, P<.001) were lower in the telehealth group. The intervention costs per patient were US$224.80 per month. Multivariate analyses revealed that age, telehealth care, and Charlson index were the independent factors for ED visits, hospitalizations, and length of hospitalization. A bootstrap method revealed the dominant cost-effectiveness of telehealth care over usual care.ConclusionsBetter cost-effectiveness and clinical outcomes were noted with the use of a fourth-generation synchronous telehealth program in patients with chronic cardiovascular diseases. The intervention costs of this new generation of telehealth program do not increase the total costs for patient care.