Min-Hui Liu

Aerobic interval training improves oxygen uptake efficiency by enhancing cerebral and muscular hemodynamics in patients with heart failure

BACKGROUND Abnormal ventilatory/hemodynamic responses to exercise contribute to functional impairment in patients with heart failure (HF). This study investigates how interval and continuous exercise regimens influence functional capacity by modulating ventilatory efficiency and hemodynamic function in HF patients. METHODS Forty-five HF patients were randomized to perform either aerobic interval training (AIT; 3-minute intervals at 40% and 80% VO(2peak)) or moderate continuous training (MCT; sustained 60% VO()for 30 min/day, 3 days/week for 12 weeks, or to a control group that received general healthcare (GHC). A noninvasive bio-reactance device was adopted to measure cardiac hemodynamics, whereas a near-infrared spectroscopy was employed to assess perfusion/O2 extraction in frontal cerebral lobe (∆[THb]FC/∆[HHb]FC) and vastus lateralis (∆[THb]VL/∆[HHb]VL), respectively. RESULTS Following the 12-week intervention, the AIT group exhibited higher oxygen uptake efficiency slope (OUES) and lower VE-VCO2 slope than the MCT and GHC groups. Furthermore, AIT, but not MCT, boosted cardiac output (CO) and increased ∆[THb]FC, ∆[THb]VL, and ∆[HHb]VL during exercise. In multivariate analyses, CO was the dominant predictor of VO(2peak). ∆[THb]FC and ∆[THb]VL, which modulated the correlation between CO and OUES, were significantly correlated with OUES. Simultaneously, ∆[THb]VL was the only factor significantly associated with VE-VCO2 slope. Additionally, AIT reduced plasma brain natriuretic peptide, myeloperoxidase, and interleukin-6 levels and increased the Short Form-36 physical/mental component scores and decreased the Minnesota Living with Heart Failure questionnaire score. CONCLUSIONS AIT effectively improves oxygen uptake efficiency by enhancing cerebral/muscular hemodynamics and suppresses oxidative stress/inflammation associated with cardiac dysfunction, and also promotes generic/disease-specific qualities of life in patients with HF.

Edema index established by a segmental multifrequency bioelectrical impedance analysis provides prognostic value in acute heart failure.

Objectives A segmental multifrequency bioelectrical impedance analysis (SMBIA) is a noninvasive and reproducible modality for estimating the fluid state. The aim of this study was to test whether the SMBIA-derived edema index provides prognostic value in patients hospitalized due to acute heart failure (AHF). Methods To estimate the 6-month prognostic value of the predischarge edema index in patients hospitalized due to AHF, 112 patients were consecutively enrolled. Both predischarge edema index and B-type natriuretic peptide (BNP) were measured. Outcome follow-up focused on heart failure-related and all-cause re-hospitalizations and all events. Results On the basis of a cutoff value of edema index of 0.390, patients were separated into two groups: edema index more than 0.390 (n = 44) and edema index of 0.390 or less (n = 68). Compared with patients with edema index 0.390 or less, those with edema index of more than 0.390 were older, had lower blood albumin and hemoglobin levels, and had higher predischarge BNP levels, functional class, incidence of diabetes mellitus, valvular cause, and diuretic use. Although edema indexes were correlated with BNP levels (r = 0.47, P < 0.0001), a mismatch was noted in 33 (29%) patients. Univariate and multivariate analysis showed that an edema index of more than 0.390 predicted a higher incidence of heart failure-related re-hospitalization [odds ratio (OR) = 4.14, confidence interval (CI) = 1.05–15.28, P = 0.04] and all events (OR = 3.97, CI = 1.4–11.25, P = 0.01). The edema index provided a prognostic value superior to that of BNP. Reducing the edema index in high-risk patients resulted in fewer heart failure-related re-hospitalizations (OR = 0.81, CI = 0.77–0.84, P < 0.001) and all events (OR = 0.8, CI = 0.76–0.85, P < 0.001). Conclusion Edema index provides 6-month prognostic values in patients hospitalized due to AHF. Reducing the edema index in high-risk patients results in better outcomes.

Surface Markers of Heterogeneous Peripheral Blood–Derived Smooth Muscle Progenitor Cells

Objective—Smooth muscle progenitor cells (SMPCs) were intriguingly shown to act as a double-edged sword in the pathogenesis of atherosclerosis. To fully clarify the roles of SMPCs in atherosclerosis, a distinct panel of SMPC surface markers is mandatory to be developed. Methods and Results—Microarray gene expression analyses were used to discover potential surface markers of SMPCs. In vitro and in vivo experiments documented that platelet-derived growth factor receptor-&bgr;, carboxypeptidase M, carbonic anhydrase 12, receptor activity-modifying protein 1, and low-density lipoprotein receptor–related protein were the 5 specific surface markers regulating various SMPC functions, including migration, extracellular matrix formation, resistance to hypoxia, and anti-inflammation. In severe combined immunodeficiency/nonobese diabetic mice after femoral arterial wire injury, injected human peripheral blood mononuclear cells contributed to substantial amount of neointimal &agr;-smooth muscle actin-positive cells, coexpressing platelet-derived growth factor receptor-&bgr;, carboxypeptidase M, carbonic anhydrase 12, receptor activity-modifying protein 1, and low-density lipoprotein receptor–related protein. Based on these markers, a novel quantification assay was developed to enumerate circulating early SMPC. Early SMPC numbers were higher in patients with unstable angina compared with those with normal coronary angiograms. In patients with acute ST-elevation myocardial infarction, different patterns of serial early SMPC changes were noted, related to different clinical presentations. Conclusion—Surface markers of heterogeneous SMPCs exhibit various functions associated with atherosclerotic pathophysiology. Quantification of surface marker–defined SMPCs provides a platform for studying SMPCs in cardiovascular diseases.

Exertional periodic breathing potentiates erythrocyte rheological dysfunction by elevating pro-inflammatory status in patients with anemic heart failure.

BACKGROUND Exertional periodic breathing (EPB) or anemia is associated with an adverse prognosis in advanced heart failure (HF). The disturbed rheological properties of erythrocytes may contribute to circulatory disorders. This study investigated whether EPB with/without anemia influences rheological/hemodynamic functions in patients with HF. METHODS According to the WHO criteria for anemia, 168 HF patients were divided into six groups: non (N)-anemic with (n=27)/without (n=56) EPB, light (L)-anemic with (n=17)/without (n=21) EPB, and moderate/several (M/S)-anemic with (n=21)/without (n=26) EPB groups. These HF patients and 30 healthy counterparts performed an incremental exercise test using a bicycle ergometer. Rheological and hemodynamic characteristics were determined by slit-flow ektacytometer and bioreactance-based device/near infrared spectrometer, respectively. RESULTS In the HF patients with EPB, both L- and M/S-anemic groups exhibited 1) higher plasma myeloperoxidase/interleukin-6 concentrations, 2) more blood senescent/spherical erythrocyte counts, 3) larger aggregability and smaller deformability of erythrocytes under shear flows, 4) higher systemic vascular resistance, which was accompanied by smaller amounts of blood distributed to cerebral/muscular tissues during exercise, 5) less VO(2peak) and ventilatory efficiency, and 6) lower Short Form-36 physical/mental component scores and higher Minnesota Living with HF questionnaire score than N-anemic group. Additionally, plasma myeloperoxidase/interleukin-6 levels were directly related to erythrocyte aggregability and inversely related to erythrocyte deformability. However, there were no significant differences in pro-inflammatory factors, rheological/hemodynamic properties, and aerobic capacity between L- and N-anemic groups in the HF patients without EPB. CONCLUSION EPB potentiates anemia-related rheological/hemodynamic dysfunctions by elevating pro-inflammatory status, reducing physical fitness in patients with HF.

Effect of multidisciplinary disease management for hospitalized heart failure under a national health insurance programme.

Aim Multidisciplinary disease management programmes (MDPs) for heart failure have been shown to be effective in Western countries. However, it is not known whether they improve outcomes in a high population density country with a national health insurance programme. Methods In total, 349 patients hospitalized because of heart failure were randomized into control and MDP groups. All-cause death and re-hospitalization related to heart failure were analyzed. The median follow-up period was approximately 2 years. Results Mean patient age was 60 years; 31% were women; and 50% of patients had coronary artery disease. MDP was associated with fewer all-cause deaths [hazard ratio (HR) = 0.49, 95% confidence interval (CI) = 0.27–0.91, P = 0.02] and heart failure-related re-hospitalizations (HR = 0.44, 95% CI = 0.25–0.77, P = 0.004). MDP was still associated with better outcomes for all-cause death (HR = 0.53, 95% CI = 0.29–0.98, P = 0.04) and heart failure-related re-hospitalization (HR = 0.46, 95% CI = 0.26–0.81, P = 0.007), after adjusting for age, diuretics, diabetes mellitus, chronic kidney disease, hypertension, sodium, and albumin. However, MDPs’ effect on all-cause mortality and heart failure-related re-hospitalization was significantly attenuated after adjusting for angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers or &bgr;-blockers. A stratified analysis showed that MDP combined with guideline-based medication had synergistic effects. Conclusions MDP is effective in lowering all-cause mortality and re-hospitalization rates related to heart failure under a national health insurance programme. MDP synergistically improves the effectiveness of guidelines-based medications for heart failure.

A correlational study of illness knowledge, self-care behaviors, and quality of life in elderly patients with heart failure.

Background: Patients with heart failure experience adverse physical symptoms that affect quality of life. The number of patients with heart failure in Taiwan has been growing in recent years. Purpose: This article examines correlations among illness knowledge, self-care behaviors, and quality of life in elderly patients with heart failure. Methods: A cross-sectional research design using three questionnaires was adopted. The study was undertaken in an outpatient department of a teaching hospital in Taiwan from January to June 2008. Potential participants aged 65 years or older were selected by a physician based on several diagnostic findings of heart failure that included an International Classification of Diseases’ code 4280 or 4289. Patients who were bedridden or had a prognosis of less than 6 months were excluded from consideration. Results: One hundred forty-one patients with heart failure were recruited. Most participants were men (51.8%), older adults (49.6% older than 71 years old), and either educated to an elementary school level or illiterate (69.5%) and have New York Heart Association class II (61.0%). Participants had an average left ventricular ejection fraction of 41.1%. The illness knowledge of participants was poor (accuracy rate: 29.3%), and most were unaware of the significance of self-care. Illness knowledge correlated with both self-care behaviors (r = −.42, p < .01) and quality of life (r = −.22, p < .01). Illness knowledge and age were identified as significant correlated factors of self-care behaviors (R2 = .22); and functional class, living independently, and age were identified as significant correlated factors of quality of life (R2 = .41). Conclusions/Implications for Practice: Participants in this study with higher self-reported self-care behaviors and quality of life were younger in age and had better illness knowledge. Furthermore, physical function and independence in daily living significantly affected quality of life. Care for patients with heart failure, particularly older adults, should focus on teaching these patients about heart failure illness and symptom management. Assisting elderly patients with heart failure to promote and maintain physical functions to handle activities of daily living independently is critical to improving patient quality of life.

Plasma P-selectin Predicts Long-term Cardiovascular Events in Hospitalized Patients with Suspected Coronary Artery Disease and Preserved Left Ventricular Function: A 10-Year Follow-Up Study

Background: A variety of biomarkers have been investigated on their values to predict cardiovascular outcomes, such as high-sensitivity C-reactive protein (hs-CRP), fibrinogen, troponin-I (TnI), and soluble P-selectin (sP-sel). By a design of head-to-head comparison, this study sought to figure out the long-term prognostic values of these parameters in patients hospitalized with suspected coronary artery disease. Methods: A total of 170 patients hospitalized with suspected coronary artery disease were enrolled and followed up for an average of 10 years. sP-sel, hs-CRP, TnI, and fibrinogen levels were measured. During the follow-up period, cardiac events were recorded including cardiac death, non-fatal myocardial infarction, and acute coronary syndromes with hospitalization. Results: For all 170 patients, with a median follow-up time of 9.86 ± 3.87 years, no parameter was able to significantly predict the occurrence of cardiac events. In subgroup analysis, an sP-sel of ≥ 63.5 ng/ml significantly predicted the development of all composite cardiac events only in patients with a left ventricular ejection fraction > 50% (n = 94, p = 0.04). However, the levels of hs-CRP, TnI, and fibrinogen did not have significant predictive values. Multivariate analysis also demonstrated the independent predictive value of sP-sel on all cardiac events (hazard ratio = 5.82, p = 0.02). All parameters, including sP-sel, could not demonstrate prognostic values in patients with a left ventricular ejection fraction ≤ 50% (n = 76). Conclusions: In this 10-year long-term follow-up study, sP-sel was demonstrated to have prognostic values in predicting the cardiac events in patients with preserved left ventricular systolic function.

Metabolic profile provides prognostic value better than galectin-3 in patients with heart failure

BACKGROUND Metabolic profiles have been shown to provide prognostic information in patients with heart failure (HF). Galectin-3 (Gal-3), indicating cardiac fibrosis, is a documented biomarker of prognosis in HF. It is unknown whether metabolic profiles provide prognostic value better than Gal-3. METHODS AND RESULTS This study analyzed 212 hospitalized HF patients, measuring metabolic score (composed by butyrylcarnitine, dimethylarginine/arginine ratio, spermidine, and total essential amino acids) and Gal-3. Endpoints were composite events (death/HF-related re-hospitalization). The median of metabolic scores and Gal-3 levels were 3.1 (1.3-5.2) and 17.8ng/mL (4.7-100ng/mL), respectively. Patients with higher metabolic scores had worse functional classes, higher atrial fibrillation incidences, levels of Gal-3 and B-type natriuretic peptide (BNP), but lower albumin levels and glomerular filtration rate. Correlations of metabolic score to Gal-3 and BNP were significant, but weak (r=0.34 and 0.41, respectively, both p<0.001). During a follow-up period of 4.2±1.4 years, there were 91 (42.9%) composite events. In univariate analysis, significant predictors of composite events were age, functional class, atrial fibrillation, levels of hemoglobin, log (Gal-3), log (BNP) and metabolic score. In multivariable analysis, adjusted for above variables, metabolic score remained a strong predictor of combined endpoints (hazard ratio=2.596, 95% confidence interval=1.649-4.087, p<0.001). C-statistics for the prediction of composite events significantly increased when metabolic score was incorporated into the model with established risk factors, BNP and Gal-3 [0.76 (0.70-0.83) vs. 0.66 (0.58-0.74), p=0.032]. CONCLUSIONS Metabolic profile provides prognostic value for HF patients better than Gal-3.

Amino Acid-Based Metabolic Panel Provides Robust Prognostic Value Additive to B-Natriuretic Peptide and Traditional Risk Factors in Heart Failure

Metabolic disturbances represent functional perturbation in peripheral tissues and predict outcomes in patients with heart failure (HF). This study developed an amino acid-based metabolic panel and sought to see whether this panel could add diagnostic and prognostic value to currently used B-type natriuretic peptide (BNP) measurements. Mass spectrometry and ultra-performance liquid chromatography were performed on 1288 participants, including 129 normal controls and 712 patients at HF stages A to D in the initial cohort and 447 stage C patients in the validation cohort. Patients were followed up for composite events (death/HF-related rehospitalization). Histidine, ornithine, and phenylalanine were 3 metabolites found strongly significant to identify patients at stage C and were adopted to develop the HOP panel. Compared to BNP, HOP had better value in discriminating the patients at different stages, especially in elderly patients and those with atrial fibrillation, high body mass index, or kidney dysfunction. HOP was correlated with the distance of 6 min walking distance better than BNP. For prognosis, HOP predicted composite events in patients at stages C and D, independent of log (BNP), age, sex, left ventricular ejection fraction, New York Heart Association functional class, HF stage, diabetes mellitus, chronic kidney disease, hypertension, hemoglobin, and albumin. Higher BNP (≥750 pg/mL) along with higher HOP (≥14) robustly predicted lower event-free survival compared to all others [hazard ratio = 3.15 (2.23–4.46), p < 0.001]. The prognostic value of HOP was confirmed in the validation cohort. In conclusion, aiming for clinical applications, this study proved that the HOP panel provides diagnostic and prognostic value additive to BNP and traditional risk factors.

Factors Associated With Inadequate Effectiveness of a Multidisciplinary Disease Management Program in Heart Failure Patients Stratified by Galectin 3 Level

Objective: This study investigated whether multidisciplinary disease management programs (MDPs) exert the same effects in heart failure (HF) patients across risk levels stratified by galectin-3 (Gal-3) level and what factors are associated with inadequate effectiveness of MDP. Methods: We used a longitudinal follow-up design based on a previous randomized trial. A total of 355 stabilized hospitalized HF patients were enrolled. The effects of MDP on death and HF-related rehospitalization were analyzed according to Gal-3 levels. Results: During the 4-year follow-up, Gal-3 levels predicted mortality and composite events (p < .001). Multivariable analysis demonstrated the event-lowering effect of MDP (hazard ratio [HR] = 0.49, p = .001 for death and HR = 0.50, p < .001 for composite events). However, the effect of MDP was inadequate for those with high Gal-3 levels (≥17.9 ng/ml), whose 4-year composite event rate was 43% in the MDP arm. Further analysis showed that, in patients with Gal-3 ≥ 17.9 ng/ml, the independent factors associated with a high composite event rate were no MDP, older age, worse New York Heart Association functional class, no angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use, higher predischarge natriuretic peptide levels, and wider QRS complexes. Conclusions: The effectiveness of MDP for HF patients at high risk was inadequate. Our findings identified the characteristics of these MDP nonresponders. Better integration of advanced care plans based on strategies guided by Gal-3 level is needed to improve care quality.