Christos Manetos

Skeletal muscle microcirculatory abnormalities are associated with exercise intolerance, ventilatory inefficiency, and impaired autonomic control in heart failure

BACKGROUND Several skeletal muscle abnormalities have been identified in patients with chronic heart failure (CHF), including endothelial dysfunction. We hypothesized that skeletal muscle microcirculation, assessed by near-infrared spectroscopy (NIRS), is impaired in CHF patients and is associated with disease severity. METHODS Eighty-three stable patients with mild-moderate CHF (72 males, mean age 54 ± 14 years, body mass index 26.7 ± 3.4 kg/m(2)) and 8 healthy subjects, matched for age, gender and body mass index, underwent NIRS with the vascular occlusion technique and cardiopulmonary exercise testing (CPET) evaluation on the same day. Tissue oxygen saturation (StO(2), %), defined as the percentage of hemoglobin saturation in the microvasculature compartments, was measured in the thenar muscle by NIRS before, during and after 3-minute occlusion of the brachial artery. Measurements included StO(2), oxygen consumption rate (OCR, %/min) and reperfusion rate (RR, %/min). All subjects underwent a symptom-limited CPET on a cycle ergometer. Measurements included VO(2) at peak exercise (VO(2)peak, ml/kg/min) and anaerobic threshold (VO(2)AT, ml/kg/min), VE/VCO(2) slope, chronotropic reserve (CR, %) and heart rate recovery (HRR(1), bpm). RESULTS CHF patients had significantly lower StO(2) (75 ± 8.2 vs 80.3 ± 6, p < 0.05), lower OCR (32.3 ± 10.4 vs 37.7 ± 5.5, p < 0.05) and lower RR (10 ± 2.8 vs 15.7 ± 6.3, p < 0.05) compared with healthy controls. CHF patients with RR ≥9.5 had a significantly greater VO(2)peak (p < 0.001), VO(2)AT (p < 0.01), CR (p = 0.01) and HRR(1) (p = 0.01), and lower VE/VCO(2) slope (p = 0.001), compared to those with RR <9.5. In a multivariate analysis, RR was identified as an independent predictor of VO(2)peak, VE/VCO(2) slope and HRR(1). CONCLUSIONS Peripheral muscle microcirculation, as assessed by NIRS, is significantly impaired in CHF patients and is associated with disease severity.

Peripheral Muscle Microcirculatory Alterations in Patients With Pulmonary Arterial Hypertension: A Pilot Study

BACKGROUND: Pulmonary microcirculation abnormalities are the main determinants of pulmonary arterial hypertension (PAH) pathophysiology. We hypothesized that PAH patients have peripheral tissue microcirculation alterations that might benefit from hyperoxic breathing. We evaluated peripheral muscle microcirculation with near-infrared spectroscopy, before and after hyperoxic breathing. METHODS: Eight PAH subjects, 8 healthy subjects (controls) matched for age, sex, and body mass index, and 16 subjects with chronic heart failure and matched for functional capacity with the PAH subjects underwent near-infrared spectroscopy. Tissue O2 saturation, defined as the hemoglobin saturation (%) in the microvasculature compartments, was measured on the thenar muscle. Then the 3-min brachial artery occlusion technique was applied before, during, and after 15 min of breathing 100% O2. We calculated the oxygen consumption rate (%/min), the reactive hyperemia time, and the time needed for tissue O2 saturation to reach its baseline value after the release of the occlusion. RESULTS: Compared to the controls, the PAH subjects had a significantly lower resting tissue O2 saturation (65.8 ± 14.9% vs 82.1 ± 4.0%, P = .005), a trend toward a lower oxygen consumption rate (35.3 ± 9.1%/min vs 43.4 ± 19.7%/min, P = .60), and a significantly higher reactive hyperemia time (3.0 ± 0.6 min vs 2.0 ± 0.3 min, P < .001). The PAH subjects also had lower tissue O2 saturation (P = .08), lower peripheral arterial oxygen saturation (P = .01), and higher reactive hyperemia time (P = .02) than the chronic heart failure subjects. After hyperoxic breathing, the PAH subjects had increased tissue O2 saturation (65.8 ± 14.9% to 71.4 ± 14.5%, P = .01), decreased oxygen consumption rate (35.3 ± 9.1%/min to 25.1 ± 6.6%/min, P = .01), and further increased reactive hyperemia time (3.0 ± 0.6 min to 4.2 ± 0.7 min, P = .007). CONCLUSIONS: The PAH subjects had substantial impairments of peripheral muscle microcirculation, decreased tissue O2 saturation (possibly due to hypoxemia), slower reactive hyperemia time, (possibly due to endothelium dysfunction), and peripheral systemic vasoconstriction. Acute hyperoxic breathing improved resting tissue O2 saturation (an expression of higher oxygen delivery) and decreased the oxygen consumption rate and reactive hyperemia time during reperfusion, possibly due to increased oxidative stress and evoked vasoconstriction.

Hormonal imbalance in relation to exercise intolerance and ventilatory inefficiency in chronic heart failure

BACKGROUND Skeletal muscle wasting is associated with altered catabolic/anabolic balance and poor prognosis in patients with chronic heart failure (CHF). This study evaluated catabolic and anabolic abnormalities in relation to disease severity in CHF patients. METHODS Forty-two stable CHF patients (34 men; aged 56±12 years, body mass index, 27±5 kg/m2) receiving optimal medical treatment underwent incremental symptom-limited cardiopulmonary exercise testing on a cycle ergometer. Blood samples were drawn within 10 days to determine serum cortisol, plasma adrenocorticotropin (ACTH), and serum dehydroepiandrosterone sulfate, insulin-like growth factor 1, growth hormone, and total testosterone in men. RESULTS Patients with higher cortisol levels presented with impaired peak oxygen uptake (Vo2 peak: 18.3±3.9 vs. 14.2±3.7 ml/kg/min, p<0.01), ventilatory (Ve) response to exercise (Ve/carbon dioxide output [Vco2] slope: 36±6 vs 30±5, p<0.01), and chronotropic reserve ([peak heart rate [HR]--resting HR/220--age--resting HR]×100%: 40±19 vs. 58±18, p=0.01) compared with those with lower serum cortisol. Cortisol was inversely correlated with Vo2 peak, (r = -0.57; p<0.01) and was correlated with Ve/Vco2 slope (r = 0.47; p<0.01) and chronotropic reserve (r = 0.44; p = 0.017). In multivariate regression analysis, cortisol was an independent predictor of Vo2peak (R2 = 0.365, F = 12.5, SE = 3.4; p≤0.001) and Ve/Vco2 slope (R2 = 0.154; F = 8.5; SE = 5.96; p = 0.006), after accounting for age, body mass index, sex, CHF etiology, creatinine, left ventricular ejection fraction, and ACTH in all patients. In men, cortisol and dehydroepiandrosterone levels were both independent predictors of Vo2peak (R2 = 0.595, F = 24.53, SE = 2.76; p<0.001) after accounting also for all measured hormones, whereas cortisol remained the only independent predictor of Ve/Vco2 slope (R2 = 0.133; F = 6.1; SE = 6.2; p = 0.02). CONCLUSIONS Enhanced catabolic status is significantly associated with exercise intolerance, ventilatory inefficiency, and chronotropic incompetence in CHF patients, suggesting a significant contributing mechanism to their limited functional status.

Neuroticism personality trait is associated with Quality of Life in patients with Chronic Heart Failure

AIM To evaluate Quality of life (QoL) in chronic heart failure (CHF) in relation to Neuroticism personality trait and CHF severity. METHODS Thirty six consecutive, outpatients with Chronic Heart Failure (6 females and 30 males, mean age: 54 ± 12 years), with a left ventricular ejection fraction ≤ 45% at optimal medical treatment at the time of inclusion, were asked to answer the Kansas City Cardiomyopathy Questionnaire (KCCQ) for Quality of Life assessment and the NEO Five-Factor Personality Inventory for personality assessment. All patients underwent a symptom limited cardiopulmonary exercise testing on a cycle-ergometer, in order to access CHF severity. A multivariate linear regression analysis using simultaneous entry of predictors was performed to examine which of the CHF variables and of the personality variables were correlated independently to QoL scores in the two summary scales of the KCCQ, namely the Overall Summary Scale and the Clinical Summary Scale. RESULTS The Neuroticism personality trait score had a significant inverse correlation with the Clinical Summary Score and Overall Summary Score of the KCCQ (r = -0.621, P < 0.05 and r = -0.543, P < 0.001, respectively). KCCQ summary scales did not show significant correlations with the personality traits of Extraversion, Openness, Conscientiousness and Agreeableness. Multivariate linear regression analysis using simultaneous entry of predictors was also conducted to determine the best linear combination of statistically significant univariate predictors such as Neuroticism, VE/VCO2 slope and VO2 peak, for predicting KCCQ Clinical Summary Score. The results show Neuroticism (β = -0.37, P < 0.05), VE/VCO2 slope (β = -0.31, P < 0.05) and VO2 peak (β = 0.37, P < 0.05) to be independent predictors of QoL. In multivariate regression analysis Neuroticism (b = -0.37, P < 0.05), the slope of ventilatory equivalent for carbon dioxide output during exercise, (VE/VCO2 slope) (b = -0.31, P < 0.05) and peak oxygen uptake (VO2 peak), (b = 0.37, P < 0.05) were independent predictors of QoL (adjusted R2 = 0.64; F = 18.89, P < 0.001). CONCLUSION Neuroticism is independently associated with QoL in CHF. QoL in CHF is not only determined by disease severity but also by the Neuroticism personality trait.

Respiratory drive and breathing pattern abnormalities are related to exercise intolerance in chronic heart failure patients

BACKGROUND Patients with chronic heart failure (CHF) are characterized by exercise intolerance and ventilatory abnormalities that are related to poor prognosis. We hypothesized that CHF patients have increased respiratory drive and abnormal breathing pattern during exercise in relation to disease severity. MATERIALS AND METHODS The study population consisted of 219 stable CHF patients and 30 healthy control subjects. All subjects underwent a symptom-limited cardiopulmonary exercise testing (CPET), pulmonary function tests, measurement of the maximal inspiratory pressure (PImax) and respiratory drive (P0.1). Measurements included peak oxygen uptake ( [Formula: see text] peak, ml/kg/min). Respiratory drive was measured by mouth occlusion pressure P0.1 and P0.1/PImax ratio at rest, and by mean inspiratory flow (VT/TI) at rest and during exercise. CHF patients were divided into 3 groups according to [Formula: see text] peak (Group A: >20, Group B: 20-16 and Group C: <16ml/kg/min). RESULTS CHF patients presented higher P0.1/PImax (4.1±3.6 vs 3.0±1.5, p=0.007) and VT/TI at rest (0.48±0.14 vs 0.41±0.10, L/s respectively, p=0.004) and lower VT/TI at peak exercise (2.17±0.66 vs 2.56±0.73, L/s, p=0.009) compared to controls. P0.1/PImax was higher in CHF Group C vs B vs A (4.9±2.9 vs 3.6±1.8 vs 3.1±1.8, respectively, p<0.001), while VT/TI at peak exercise was lower (1.71±0.43 vs 2.15±0.52 vs 2.65±0.64, L/s, respectively, p<0.001). CONCLUSIONS CHF patients present increased respiratory drive at rest and abnormal breathing pattern during exercise in relation to CHF severity.

Attenuated Microcirculatory Response to Maximal Exercise in Patients With Chronic Heart Failure.

PURPOSE: Exercise training programs improve microcirculatory alternations in patients with chronic heart failure (CHF). However less is known about the acute effect of maximum exercise on the skeletal muscle microcirculation. We aimed to assess the effect of acute exercise on peripheral microcirculation of patients with CHF, as assessed by near-infrared spectroscopy with vascular occlusion technique. METHODS: Tissue oxygenation was evaluated in 8 stable patients with CHF (7 males; mean age, 60 ± 9 years; body mass index, 26.3 ± 3.8 kg/m2) and 8 healthy subjects (matched for age, sex, and body mass index) before and after cardiopulmonary exercise testing. Tissue oxygen saturation (StO2), StO2peak, oxygen consumption rate, and endothelial function (reperfusion rate), before and after maximum exercise, were assessed. RESULTS: Patients with CHF had lower StO2 and reperfusion rate compared with healthy subjects (71.4% ± 9.8% vs 81.0% ± 5.4% and 9 ± 1 %/min vs 13.9 ± 5.8%/min, respectively; P < .05) at rest. Oxygen consumption rate increased after exercise in patients with CHF and healthy subjects (from −31.7 ± 8.2 to −43.7 ± 12.7 and from −35.7 ± 6.7 to −42.4 ± 6.4, respectively; P < .05). StO2 decreased significantly after maximal exercise in patients with CHF (from 71.4 ± 9.8 to 65.2 ± 12.7; P < .05), whereas it returned to the preexercise values in healthy subjects (from 81.0 ± 5.4 to 80.3 ± 7.0). There was a significant between-group difference (P < .05). CONCLUSIONS: Patients with CHF present microcirculatory alternations. Acute exercise exerts an effect on microcirculation in peripheral, nonexercising muscles, with altered response in patients with CHF compared with healthy subjects.

Changes in skeletal muscle microcirculation after a hemodialysis session correlates with adequacy of dialysis.

Background Monitoring of the microcirculation may add additional information in terms of improving the adequacy of hemodialysis (HD) for patients. Withdrawal of liquid and complement activation during a HD session reduces the external pressure on the microcirculation and leads to an increased dilatation of the peripheral capillaries. The purposes of this study were to assess the effect of a single HD or hemodiafiltration session on the thenar microcirculation in patients with end-stage renal disease (ESRD) with or without diabetes, investigate the possible relationship between changes in the microcirculation and adequacy of dialysis (including Kt/V and parameters indicating secondary hyperparathyroidism), and compare microcirculation measurements obtained from patients with ESRD and those from healthy controls. Methods This pilot prospective observational study including eleven patients with ESRD on maintenance HD (nine men of mean age 73±10.5 years, ten [91%] with hypertension), nine patients with ESRD on maintenance hemodiafiltration (six men of mean age 65.5±13.2 years, five [55.5%] with diabetes and four [44.5%] with hypertension), and eight healthy volunteers. Two paired microcirculation assessments were recorded for each HD patient before and after a dialysis session. Near infrared spectroscopy and the vascular occlusion test were used to assess the microcirculation, and blood work samples were collected before and after dialysis when the pump slowed down. Results Patients with ESRD showed an increase in thenar cell metabolism at rest after a 4-hour HD session, and changes in cell metabolism correlated with the Kt/V of the session. Pre-dialysis tissue oxygen saturation over the 4-hour HD session correlated with pre-dialysis serum calcium and parathyroid hormones. Vascular reactivity was lower in ESRD patients receiving HD or hemodiafiltration than in healthy controls. Conclusion Improvement in skeletal muscle microcirculation noted after a HD session was related to adequacy of dialysis. Evaluation of the microcirculation may provide additional information for management of patients on HD and identify novel targets for treatment. These preliminary findings need to be tested using a larger data set.

REVERSAL OF RESPIRATORY MUSCLES DYSFUNCTION AND EXERCISE CAPACITY IMPROVEMENT AFTER CONTINUOUS-FLOW LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION

Methods: Eight consecutive CHF patients (6Males/2Females, mean age: 45±15 years) were enrolled in the study after LVAD (HeartMate II) implantation as destination therapy (N=4, Males, Ischemic CHF) and as a bridge to transplantation / recovery (N=4, Non-ischemic CHF). All patients received optimal “reverse” remodelling medical treatment including clenbuterol in the non-ischemic CHF group. Patients were evaluated with the use of a cardiopulmonary exercise testing and respiratory function tests at 1, 3 and 6 months.

P01-306 - Trait anxiety predicts quality of life in patients with heart failure independently of the severity of disease

Objectives The objective of this study was to investigate the relationship between anxiety personality trait, Quality of Life (QoL) and severity of disease in a Greek population of patients with Chronic Heart Failure (CHF). Methods Twenty-seven consecutive CHF outpatients (22 males, 5 females; age: 56±12) were asked to answer the Greek version of the Trait Anxiety subscale of the State-Trait Anxiety Inventory (STAI), as a part of a thorough cardiological and psychiatric clinical evaluation. QoL was assessed with the Greek version of the disease-specific Kansas City Cardiomyopathy Questionnaire (KCCQ). Multiple linear regression was conducted to determine the best linear combination of Trait Anxiety scores and severity of disease scores, for predicting KCCQ Overall Summary Score. The indices of disease severity that were used were New York Heart Association (NYHA) class in the first model and VO2peak in the second model. Results For the first model (adjusted R2=0.557, F(2,20)=14.816, p For the second model (adjusted R2=0.616, F(2,19)=17.848, p Conclusions Trait Anxiety predicts QoL independently of disease severity in CHF and therefore should be considered in the assessment of patient health status as well as in the design of treatment interventions and rehabilitation.