Tieh-Cheng Fu

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.

Effects of normoxic and hypoxic exercise regimens on cardiac, muscular, and cerebral hemodynamics suppressed by severe hypoxia in humans

Hypoxic preconditioning prevents cerebrovascular/cardiovascular disorders by increasing resistance to acute ischemic stress, but severe hypoxic exposure disturbs vascular hemodynamics. This study compared how various exercise regimens with/without hypoxia affect hemodynamics and oxygenation in cardiac, muscle, and cerebral tissues during severe hypoxic exposure. Sixty sedentary males were randomly divided into five groups. Each group (n = 12) received one of five interventions: 1) normoxic (21% O(2)) resting control, 2) hypoxic (15% O(2)) resting control, 3) normoxic exercise (50% maximum work rate under 21% O(2); N-E group), 4) hypoxic-relative exercise (50% maximal heart rate reserve under 15% O(2); H-RE group), or 5) hypoxic-absolute exercise (50% maximum work rate under 15% O(2); H-AE group) for 30 min/day, 5 days/wk, for 4 wk. A recently developed noninvasive bioreactance device was used to measure cardiac hemodynamics, and near-infrared spectroscopy was used to assess perfusion and oxygenation in the vastus lateralis (VL)/gastrocnemius (GN) muscles and frontal cerebral lobe (FC). Our results demonstrated that the H-AE group had a larger improvement in aerobic capacity compared with the N-E group. Both H-RE and H-AE ameliorated the suppression of cardiac stroke volume and the GN hyperemic response (Delta total Hb/min) and reoxygenation rate by acute 12% O(2) exposure. Simultaneously, the two hypoxic interventions enhanced perfusion (Delta total Hb) and O(2) extraction [Delta deoxyHb] of the VL muscle during the 12% O(2) exercise. Although acute 12% O(2) exercise decreased oxygenation (Delta O(2)Hb) of the FC, none of the 4-wk interventions influenced the cerebral perfusion and oxygenation during normoxic/hypoxic exercise tests. Therefore, we conclude that moderate hypoxic exercise training improves cardiopulmonary fitness and increases resistance to disturbance of cardiac hemodynamics by severe hypoxia, concurrence with enhancing O(2) delivery/utilization in skeletal muscles but not cerebral tissues.

Suppression of cerebral hemodynamics is associated with reduced functional capacity in patients with heart failure

This investigation elucidated the underlying mechanisms of functional impairments in patients with heart failure (HF) by simultaneously comparing cardiac-cerebral-muscle hemodynamic and ventilatory responses to exercise among HF patients with various functional capacities. One hundred one patients with HF [New York Heart Association HF functional class II (HF-II, n = 53) and functional class III (HF-III, n = 48) patients] and 71 normal subjects [older control (O-C, n = 39) and younger control (Y-C, n = 32) adults] performed an incremental exercise test using a bicycle ergometer. A recently developed noninvasive bioreactance device was adopted to measure cardiac hemodynamics, and near-infrared spectroscopy was employed to assess perfusions in the frontal cerebral lobe (Δ[THb](FC)) and vastus lateralis muscle (Δ[THb](VL)). The results demonstrated that the Y-C group had higher levels of cardiac output, Δ[THb](FC), and Δ[THb](VL) during exercise than the O-C group. Moreover, these cardiac/peripheral hemodynamic responses to exercise in HF-III group were smaller than those in both HF-II and O-C groups. Although the change of cardiac output caused by exercise was normalized, the amounts of blood distributed to frontal cerebral lobe and vastus lateralis muscle in the HF-III group significantly declined during exercise. The HF-III patients had lower oxygen-uptake efficiency slopes (OUES) and greater Ve-Vo(2) slopes than the HF-II patients and age-matched controls. However, neither hemodynamic nor ventilatory response to exercise differed significantly between the HF-II and O-C groups. Cardiac output, Δ[THb](FC), and Δ[THb](VL) during exercise were directly related to the OUES and Vo(2peak) and inversely related to the Ve-Vco(2) slope. Moreover, cardiac output or Δ[THb](FC) was an effect modifier, which modulated the correlation status between Δ[THb](VL) and Ve-Vco(2) slope. We concluded that the suppression of cerebral/muscle hemodynamics during exercise is associated with ventilatory abnormality, which reduces functional capacity in patients with HF.

Aerobic Interval Training Elicits Different Hemodynamic Adaptations Between Heart Failure Patients with Preserved and Reduced Ejection Fraction.

ObjectiveThis investigation explored how aerobic interval training influences central or peripheral hemodynamic response(s) to exercise in patients with heart failure (HF) with preserved ejection fraction (HFpEF) or those with HF with reduced ejection fraction (HFrEF). DesignOne hundred twenty HF patients were divided into four groups: HFpEF and HFrEF with aerobic interval training (3-min intervals at 40% and 80% VO2peak for 30 mins/day, 3 days/wk for 12 wks) and general health care groups. Exercise hemodynamics in the heart, frontal cerebral lobe, and vastus lateralis muscle, and oxygenation in the frontal cerebral lobe and vastus lateralis muscle were measured before and after the intervention. ResultsAerobic interval training significantly (1) improved pumping function with enhanced peak cardiac power index in the HFrEF group and improved diastolic function with reduction of the E/E′ ratio in the HFpEF group, (2) increased blood distribution to the frontal cerebral lobe/vastus lateralis muscle and O2 extraction by vastus lateralis muscle during exercise in the HFpEF group compared with the HFrEF group, (3) heightened VO2peak in both HFpEF and HFrEF groups and lowered the VE/VCO2 slope in the HFpEF group, and (4) increased the Short Form-36 physical/mental component scores and decreased the Minnesota Living with Heart Failure questionnaire score in both HFpEF and HFrEF groups. ConclusionsAerobic interval training effectively enhances cardiac hemodynamic response to exercise in HFrEF patients while increasing the delivery/use of O2 to exercising skeletal muscles and frontal cerebral lobe tissues in HFpEF patients, thereby improving global/disease-specific quality-of-life measures in these HF patients.

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.

Effect of aerobic interval training on erythrocyte rheological and hemodynamic functions in heart failure patients with anemia

BACKGROUND Anemia disturbs hemorheological/hemodynamic properties, whereas aerobic interval training (AIT) achieves a superior aerobic fitness in patients with heart failure (HF). This study investigated whether AIT influences functional capacity by modulating hemorheological/hemodynamic functions in HF patients with/without anemia. METHODS Sixty HF patients were divided into non-anemic (HF-NA, hemoglobin >/= 12 g/dL in women/ >/= 13 g/dL in men; n=30) and anemic (HF-A, hemoglobin<11 g/dL in women/<12 g/dL in men; n=30) groups, and 30 normal counterparts were enrolled as a control group. These HF patients performed AIT (3-minute intervals at 40% and 80%VO(2peak)) on a bicycle ergometer for 30 min/day, 3 days/week for 12 weeks. Erythrocyte rheological and central/peripheral hemodynamic characteristics were determined by slit-flow ektacytometer and bioreactance-based device/near infrared spectrometer, respectively. RESULTS In both HF-NA and HF-A groups, the AIT regimen 1) reduced blood senescent/spherical erythrocyte counts, 2) diminished the values of critical shear stresses for disaggregation and half-maximal deformation of erythrocytes, 3) enhanced cardiac output during exercise, 4) heightened VO(2peak) and O2 uptake efficiency slope (OUES), and 5) decreased plasma myeloperoxidase and interleukin-6 levels. However, AIT increased the amounts of blood distributed to the frontal cerebral lobe and vastus lateralis muscle during exercise in HF-NA group but not in HF-A group. Additionally, HF-A group exhibited fewer the enhancements of VO(2peak) and OUES caused by AIT than HF-NA group did. CONCLUSION AIT improves aerobic capacity and efficiency by depressing aggregability and enhancing deformability of erythrocytes in patients with HF. However, anemic comorbidity attenuates the adaptations of cerebral/muscular hemodynamic responses to exercise following this regimen.

Effects of normoxic and hypoxic exercise regimens on monocyte-mediated thrombin generation in sedentary men.

Exercise and hypoxia paradoxically modulate vascular thrombotic risks. The shedding of procoagulant-rich microparticles from monocytes may accelerate the pathogenesis of atherothrombosis. The present study explores the manner in which normoxic and hypoxic exercise regimens affect procoagulant monocyte-derived microparticle (MDMP) formation and monocyte-promoted thrombin generation (TG). Forty sedentary healthy males were randomized to perform either normoxic (NET; 21% O2, n=20) or hypoxic (HET; 15% O2, n=20) exercise training (60% VO(2max)) for 30 min/day, 5 days/week for 5 weeks. At rest and immediately after HET (100 W under 12% O2 for 30 min), the MDMP characteristics and dynamic TG were measured by flow cytometry and thrombinography respectively. The results demonstrated that acute 12% O2 exercise (i) increased the release of coagulant factor V (FV)/FVIII-rich, phosphatidylserine (PS)-exposed and tissue factor (TF)-expressed microparticles from monocytes, (ii) enhanced the peak height and rate of TG in monocyte-rich plasma (MRP) and (iii) elevated concentrations of norepinephrine/epinephrine, myeloperoxidase (MPO) and interleukin-6 (IL-6) in plasma. Following the 5-week intervention, HET exhibited higher enhancements of peak work-rate and cardiopulmonary fitness than NET did. Moreover, both NET and HET decreased the FV/FVIII-rich, PS-exposed and TF-expressed MDMP counts and the peak height and rate of TG in MRP following the HET. However, HET elicited more suppression for the HE (hypoxic exercise)-enhanced procoagulant MDMP formation and dynamic TG in MPR and catecholamine/peroxide/pro-inflammatory cytokine levels in plasma than NET. Hence, we conclude that HET is superior to NET for enhancing aerobic capacity. Furthermore, HET effectively suppresses procoagulant MDMP formation and monocyte-mediated TG under severe hypoxic stress, compared with NET.

Central and Peripheral Hemodynamic Adaptations During Cardiopulmonary Exercise Test in Heart Failure Patients With Exercise Periodic Breathing.

Some heart failure (HF) patients develop ventilatory oscillation which is composed of exercise periodic breathing (EPB) and sleep apnea. The ventilatory oscillation is associated with exercise intolerance. This study employed an integrated monitoring system to elucidate the way of central and peripheral hemodynamic adaption responding to exercise. This study recruited 157 HF patients to perform exercise testing using a bicycle ergometer. A noninvasive bio-reactance device was adopted to measure cardiac hemodynamics, whereas a near-infrared spectroscopy (NIRS) was used to assess perfusion and O2 extraction in the frontal cerebral lobe (FC) and vastus lateralis muscle (VL) during exercise respectively. Furthermore, quality of life (QoL) was measured with the Short Form-36 (SF-36) and the Minnesota Living with Heart Failure questionnaires (MLHFQ). The patients were divided into an EPB group (n = 65) and a non-EPB group (n = 92) according to their ventilation patterns during testing. Compared to their non-EPB counterparts, the patients with EPB exhibited 1) impaired aerobic capacity with a smaller peak oxygen consumption (VO2peak) and oxygen uptake efficiency slopes; 2) impaired circulatory and ventilatory efficiency with relatively high cardiac output and ventilation per unit workload; 3) impaired ventilatory/hemodynamic adaptation in response to exercise with elevated deoxyhemoglobin levels in the FC region; and 4) impaired QoL with lower physical component scores on the SF-36 and higher scores on the MLHFQ. In conclusion, EPB may reduce circulatory-ventilatory-hemodynamic efficiency during exercise, thereby impairing functional capacity in patients with HF.

High-intensity interval training enhances mitochondrial bioenergetics of platelets in patients with heart failure

OBJECTIVE Exercise improves cardiopulmonary fitness and reduces the risk of vascular thrombosis in patients with cardiovascular diseases. In platelets, mitochondria carry out cellular bioenergetics and thrombogenesis. This study aimed to elucidate the effect of high-intensity interval training (HIIT) on systemic aerobic capacity and platelet mitochondrial bioenergetics in patients with heart failure (HF). METHODS Thirty-four randomly selected HF patients engaged in HIIT (3-min intervals at 40% and 80% of VO2peak, n = 17) for 30 min/day, 3 days/week for 12 weeks, or to a control group that received general healthcare (GHC; n = 17). Systemic aerobic capacity (i.e., peak O2 consumption, VO2peak) and platelet mitochondrial O2 consumption rate (OCR) in the HF patients were measured through automatic gas analysis and high-resolution respirometry, respectively. RESULTS The HIIT group exhibited higher VO2peak and O2 uptake efficiency slope and lower VE-VCO2 slope after 12-week intervention, compared to those of the GHC group. Moreover, the HIIT regimen increased the maximal and reserve OCR capacities, enhanced the Complex I- and II-mediated OCRs, and elevated the bioenergetic health index in platelet mitochondria; however, these effects were not observed with the GHC regimen. Additionally, the VO2peak levels were positively correlated with the maximal and reserve OCR capacities and Complex I- and II-mediated OCRs in platelet mitochondria. CONCLUSION Platelet mitochondrial function is an ideal bioenergetic indicator in patients with HF. HIIT for 12 weeks elevates platelet mitochondrial OCRs via increasing Complex I and II activities. Moreover, systemic aerobic capacity is positively associated with platelet mitochondrial OCRs in HF patients.