Circuit resistance training in chronic heart failure improves skeletal muscle mitochondrial ATP production rate--a randomized controlled trial

BackgroundWe aimed to determine the role of skeletal muscle mitochondrial ATP production rate (MAPR) in relation to exercise tolerance after resistance training (RT) in chronic heart failure (CHF).Methods and ResultsThirteen CHF patients (New York Heart Association functional class 2.3 ± 0.5; Left ventricular ejection fraction 26 ± 8%; age 70 ± 8 years) underwent testing for peak total body oxygen consumption (VO_2peak), and resting vastus lateralis muscle biopsy. Patients were then randomly allocated to 11 weeks of RT (n = 7), or continuance of usual care (C; n = 6), after which testing was repeated. Muscle samples were analyzed for MAPR, metabolic enzyme activity, and capillary density. VO_2peak and MAPR in the presence of the pyruvate and malate (P+M) substrate combination, representing carbohydrate metabolism, increased in RT (P < .05) and decreased in C (P < .05), with a significant difference between groups (VO_2peak, P = .005; MAPR, P = .03). There was a strong correlation between the change in MAPR and the change in peak total body oxygen consumption (VO_2peak) over the study (r = 0.875; P < .0001), the change in MAPR accounting for 70% of the change in VO_2peak.ConclusionsThese findings suggest that mitochondrial ATP production is a major determinant of aerobic capacity in CHF patients and can be favorably altered by muscle strengthening exercise.     

The relationship between resting lung-to-lung circulation time and peak exercise capacity in chronic heart failure patients

BackgroundPeak exercise capacity (VO_2peak) is a measure of the severity of chronic heart failure (CHF); however, few indices of resting cardiopulmonary function have been shown to predict VO_2peak. A prolonged circulation time has been suggested as an index of increased severity of CHF. The aim of this study was to investigate the relationship between resting lung-to-lung circulation time (LLCT) and VO_2peak in CHF.Methods and ResultsThirty CHF patients (59 ± 13 years, New York Heart Association: 1.9 ± 1.0) undertook the study. Each subject completed resting pulmonary and echocardiography measures and an incremental exercise test. LLCT was measured using the reappearance of end-tidal acetylene (P_ET,C₂H₂) after a single inhalation. Univariate and multivariate stepwise linear regression was used to determine the predictors of VO_2peak. Univariate correlates of VO_2peak (group mean 1.53 ± 0.44 L/min⁻¹) included LLCT (r = −0.75), inspiratory capacity (r = 0.41), ejection fraction (r = 0.33), peak early flow velocity (r = −0.39), and the ratio of early to late flow velocity (r = −0.31). LLCT was the only independent predictor where VO_2peak = 3.923–0.045 (LLCT); r² = 54%.ConclusionsThese results suggest that resting LLCT determined using the soluble inert gas technique represents a simple, noninvasive method that provides additional information regarding exercise capacity in CHF.     

The Influence of Sex Differences on Cardiopulmonary Exercise Metrics Following Heart Transplant

BackgroundPrevious work has shown sex-related differences in cardiopulmonary responses in patients with heart failure (HF); however, sex differences following heart transplant (HTx) have not been examined. Thus, we hypothesized women would demonstrate lower peak oxygen uptake (VO_2peak) but similar ventilatory efficiency (V_E/VCO₂ slope) compared with men prior to HTx. Furthermore, we hypothesized that, following HTx, women would exhibit greater improvements in VO_2peak and V_E/VCO₂ slope compared with men.MethodsHTx patients with cardiopulmonary exercise testing (CPET) between 2007 and 2016 were included. Pre-HTx CPET occurred within 24 months pre-HTx with post-HTx CPET within 12 months following HTx. VO_2peak was measured via standard protocol. V_E/VCO₂ slope was calculated using rest-peak ventilation (V_E) and carbon dioxide production (VCO₂).ResultsEighty-eight patients (Men [M]: n = 63, age: 55 ± 12 years; Women [W]: n = 25, age: 47 ± 11 years) were assessed. Pre-HTx VO_2peak (M: 13.9 ± 5.0 vs W: 11.6 ± 3.9 mL/kg/min, P = 0.17) and V_E/VCO₂ slope (M: 42 ± 12 vs W: 46 ± 18, P = 0.53) were not different between sexes. Overall, VO_2peak (Pre: 13.3 ± 4.8 vs Post: 18.4 ± 4.8 mL/kg/min, P < 0.01) and V_E/VCO₂ slope (Pre: 43 ± 14 vs Post: 37 ± 6, P = 0.02) improved following HTx. Post-VO_2peak (M: 19.0 ± 4.8 vs W: 16.8 ± 4.5 mL/kg/min, P = 0.24) and V_E/VCO₂ slope (M: 37 ± 6 vs W: 37 ± 7, P = 0.99) and delta VO_2peak (M: 5.0 ± 4.8 vs W: 5.3 ± 4.9 mL/kg/min, P = 0.85) and V_E/VCO₂ slope (M: –5 ± 11 vs W: –9 ± 17, P = 0.29) were not different between sexes.ConclusionsThese data demonstrate that cardiopulmonary improvements following HTx patients occur for both sexes. Importantly, women show similar significant functional improvements following HTx compared with men.     

Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure

BackgroundInsulin resistance is present in the setting of congestive heart failure. Glucagon-like peptide-1 (GLP-1) is a naturally occurring incretin with both insulinotropic and insulinomimetic properties.Methods and ResultsWe investigated the safety and efficacy of a 5-week infusion of GLP-1 (2.5 pmol/kg/min) added to standard therapy in 12 patients with New York Heart Association class III/IV heart failure and compared the results with those of 9 patients with heart failure on standard therapy alone. Echocardiograms, maximum myocardial ventilation oxygen consumption (VO₂ max), 6-minute walk test, and Minnesota Living with Heart Failure quality of life score (MNQOL) were assessed. Baseline demographics, background therapy, and the degree of left ventricular dysfunction were similar between groups. GLP-1 significantly improved left ventricular ejection fraction (21 ± 3% to 27 ± 3% P < .01), VO₂ max (10.8 ± .9 ml/O₂/min/kg to 13.9 ± .6 ml/O₂/min/kg; P < .001), 6-minute walk distance (232 ± 15 m to 286 ± 12 m; P < .001) and MNQOL score (64 ± 4 to 44 ± 5; P < .01). Benefits were seen in both diabetic and non-diabetic patients. There were no significant changes in any of the parameters in the control patients on standard therapy. GLP-1 was well tolerated with minimal episodes of hypoglycemia and gastrointestinal side effects.ConclusionChronic infusion of GLP-1 significantly improves left ventricular function, functional status, and quality of life in patients with severe heart failure.     

Moderate Continuous and Modified High-Intensity Interval Training in Patients With Left Ventricular Assist Devices: The Prospective Train-the-LVAD Trial

BackgroundHigh-intensity interval training (HIIT) of 4 minutes at 80%–90% of peak oxygen consumption (VO_2peak) has been shown to be feasible in patients with left ventricular assist devices (LVADs). The effect of shorter bouts of HIIT, which reduce the anaerobic burden, has not been investigated compared to moderate continuous training (MCT).Methods and ResultsWe conducted a prospective, monocentric study (NCT05121077) randomizing patients with LVADs into 20 minutes of MCT (n = 10) or short bouts (≤ 90 seconds) of HIIT (n = 10) following cardiopulmonary exercise testing at 50%–60% and 80%–90% of VO_2peak. Each of the 18 supervised sessions (3×/week, t_0–t₁) included 10 minutes of strengthening training. The primary outcome was the increase of VO_2peak in the 2 groups between t₀ and t₁. Secondary outcomes were changes in the 12-item Kansas City Cardiomyopathy Questionnaire, the 6-minute walk distance and the percentage of VO_2peak at the first ventilatory threshold. VO_2peak significantly increased with HIIT (13.0 ± 4.6mL/kg/min vs 14.6 ± 4.3mL/kg/min; P = 0.037), but not with MCT (11.8 ± 3.3mL/kg/min vs 13.1 ± 3.3mL/kg/min; P = 0.322), without between-group differences (P = 0.853). Secondary outcomes improved from t_0–t₁ in MCT and HIIT, without differences between the groups.ConclusionsShort bouts of HIIT are feasible, and they improved VO_2peak and functional parameters in patients in this pilot prospective study.     

The Effects of Race on Peak Oxygen Consumption and Survival in Patients With Systolic Dysfunction

BackgroundThe relationship of peak exercise oxygen consumption (VO₂) to survival in black heart failure (HF) patients is not well established. We examined the effects of race on peak VO₂ values and survival in HF patients with systolic dysfunction.Methods and ResultsThis study evaluated consecutive ambulatory HF patients who underwent symptom-limited stress tests with breath-by-breath expired gas analyses using ramped treadmill protocols. The relationship between cardiopulmonary exercise parameters and patient transplant-free survival was assessed by race. This study included 580 HF patients (mean age 52 ± 12 years; 28% females; 22% blacks; mean left ventricular ejection fraction 26 ± 12%; mean body mass index 28.7 ± 5.4; 73% on β-blocker). Black patients had a significantly lower peak VO₂ than white patients (14.2 ± 5.2 versus 16.4 ± 7.0; P < .0001), despite adjusting for identified covariates. However, there was no significant difference in the 1-year transplant-free survival between black and white HF patients (87% versus 85%; P = NS). Peak VO₂ was significantly associated with survival in both racial groups.ConclusionsBlack HF patients had significantly lower peak VO₂, but yet had equivalent survival rates at 1 year. Further study is warranted to clarify the impact of these racial differences on the timing of cardiac transplantation black HF patients.     

Enhanced Echo Intensity of Skeletal Muscle Is Associated With Exercise Intolerance in Patients With Heart Failure

BackgroundSkeletal muscle is quantitatively and qualitatively impaired in patients with heart failure (HF), which is closely linked to lowered exercise capacity. Ultrasonography (US) for skeletal muscle has emerged as a useful, noninvasive tool to evaluate muscle quality and quantity. Here we investigated whether muscle quality based on US-derived echo intensity (EI) is associated with exercise capacity in patients with HF.Methods and ResultsFifty-eight patients with HF (61 ± 12 years) and 28 control subjects (58 ± 14 years) were studied. The quadriceps femoris echo intensity (QEI) was significantly higher and the quadriceps femoris muscle thickness (QMT) was significantly lower in the patients with HF than the controls (88.3 ± 13.4 vs 81.1 ± 7.5, P= .010; 5.21 ± 1.10 vs 6.54 ±1.34 cm, P< .001, respectively). By univariate analysis, QEI was significantly correlated with age, peak oxygen uptake (VO₂), and New York Heart Association class in the HF group. A multivariable analysis revealed that the QEI was independently associated with peak VO₂ after adjustment for age, gender, body mass index, and QMT: β-coefficient = −11.80, 95%CI (−20.73, −2.86), P= .011.ConclusionEnhanced EI in skeletal muscle was independently associated with lowered exercise capacity in HF. The measurement of EI is low-cost, easily accessible, and suitable for assessment of HF-related alterations in skeletal muscle quality.     

Increased High Mobility Group Box-1 Protein Levels are Associated With Impaired Cardiopulmonary and Echocardiographic Findings After Acute Myocardial Infarction

BackgroundSeveral markers of systemic inflammation seem to play an active role in the pathophysiology of acute coronary syndrome and its evolution. High mobility group box-1 (HMGB-1), a ubiquitous nuclear protein constitutively expressed in quiescent cells, was recently recognized as a newer critical mediator of inflammatory diseases. The present study aimed to evaluate the possible association between HMGB-1 levels and structural and functional indices of cardiovascular performance such as cardiopulmonary and Doppler-echocardiography indices in patients after acute myocardial infarction (MI).Methods and ResultsFifty-four consecutive patients (mean age 58.3 years, 83% males) recovering from acute MI were included in the study protocol. All patients underwent Doppler-echocardiography, cardiopulmonary exercise, and HMGB-1 assay. HMGB-1 levels in acute MI patients were significantly higher compared with age- and body mass index–matched controls (14.8 ± 6.8 vs. 2.3 ± 1.0 ng/mL, P < .0001, respectively). Postinfarction patients showed oxygen consumption at peak exercise (VO_2peak) = 14.4 ± 4.2 mL·kg·min and a slope of increase in ventilation over carbon dioxide output (VE/VCO_2slope) = 32.1 ± 6.2, whereas Doppler-echocardiography values were: left ventricular end-diastolic volume (LVEDV) = 53.4 ± 8.2 mL/m²; left ventricular ejection fraction (LVEF) = 41.7 ± 7.0%. Multiple linear regression analysis (stepwise method) showed that VO_2peak (β = –0.276, P = .012), VE/VCO_2slope (β = 0.244, P = .005), LVEDV (β = 0.267, P = .018), peak creatine kinase-MB (β = 0.339, P = .004), peak Troponin I (β = 0.244, P = .002), and LVEF (β = –0.312, P = .021) were significantly associated with HMGB-1 levels.ConclusionsThe present study demonstrated that in postinfarction patients, HMGB-1 levels were significantly higher compared with controls, and significantly correlated with cardiopulmonary and Doppler-echocardiography parameters.     

Losartan improves heart rate variability and heart rate turbulence in heart failure due to ischemic cardiomyopathy

BackgroundHeart rate variability (HRV) and heart rate turbulence are known to be disturbed and associated with excess mortality in heart failure. The aim of this study was to investigate whether losartan, when added on top of β-blocker and angiotensin-converting enzyme inhibitor (ACEI) therapy, could improve these indices in patients with systolic heart failure.Methods and ResultsSeventy-seven patients (mean age 60.4 ± 8.0, 80.5% male) with ischemic cardiomyopathy (mean ejection fraction 34.5 ± 4.4%) and New York Heart Association Class II-III heart failure symptoms, already receiving a β-blocker and an ACEI, were randomly assigned to either open-label losartan (losartan group) or no additional drug (control group) in a 2:1 ratio and the patients were followed for 12 weeks. The HRV and heart rate turbulence indices were calculated from 24-hour Holter recordings both at the beginning and at the end of follow-up. The baseline clinical characteristics, HRV, and heart rate turbulence indices were similar in the 2 groups. At 12 weeks of follow-up, all HRV parameters except pNN50 increased (SDNN: 113.2 ± 34.2 versus 127.8 ± 24.1, P = .001; SDANN: 101.5 ± 31.7 versus 115.2 ± 22.0, P = .001; triangular index: 29.9 ± 11.1 versus 34.2 ± 7.9, P = .008; RMSSD: 29.1 ± 20.2 versus 34.3 ± 23.0, P = .009; NN50: 5015.3 ± 5554.9 versus 6446.7 ± 6101.1, P = .024; NN50: 5.65 ± 6.41 versus 7.24 ± 6.99, P = .089; SDNNi: 45.1 ± 13.3 versus 50.3 ± 14.5, P = .004), turbulence onset decreased (−0. 61 ± 1.70 versus −1.24 ± 1.31, P = .003) and turbulence slope increased (4.107 ± 3.881 versus 5.940 ± 4.281, P = .004) significantly in the losartan group as compared with controls.ConclusionsA 12-week-long losartan therapy significantly improved HRV and heart rate turbulence in patients with Class II-III heart failure and ischemic cardiomyopathy already on β-blockers and ACEI.     

Short-term Prognostic Value of Heart Failure Diagnosis in a Contemporary Cohort of Patients With Adult Congenital Heart Disease

BackgroundHeart failure (HF) is the primary cause of premature death in adult congenital heart disease (ACHD). This study aimed to describe the impact of a HF diagnosis on short-term prognosis and to investigate the added prognostic value of an HF diagnosis to the ACHD Anatomic and Physiologic classification (ACHD-AP).MethodsThis study included 3995 patients followed in a tertiary care centre (last follow-up after January 1, 2010). Survival curves were plotted, and predictors of the primary end point (death, heart transplantation, or ventricular assist device [VAD]) were identified with the use of Cox proportional hazard models and compared with the use of Harrell’s C-statistic.ResultsMean age at baseline was 35.7 ± 13.3 years. The prevalence of ACHD-HF was 6.4%. During a median follow-up of 3.1 years (IQR 2.1-3.6 years), 27.3% of ACHD-HF patients reached the primary end point, compared with 1.4% of ACHD patients without HF. Event-free survivals were 78.3%, 61.9%, and 57.5% at 1, 3, and 5 years in ACHD-HF patients, compared with 99.3%, 98.3%, and 98.0% in ACHD patients without HF (P < 0.001). An HF diagnosis (HR 6.9, 95% CI 4.3-11.2) and the physiologic classification (HR 2.6, 95% CI 1.9-3.7) were independently associated with the primary end point. The addition of HF to the ACHD-AP classification yielded a Harrell’s C-index of 0.8631, providing a significant improvement over the ACHD-AP classification alone (P = 0.0003).ConclusionsThe risk of mortality, transplantation, or VAD is increased in ACHD-HF patients. An HF diagnosis appears to be a valuable prognostic marker in addition to the ACHD-AP classification.     

Reduction in Circulating Testosterone Relates to Exercise Capacity in Men With Chronic Heart Failure

BackgroundWe investigated whether anabolic deficiency was linked to exercise intolerance in men with chronic heart failure (CHF). Anabolic hormones (testosterone, dehydroepiandrosterone sulfate, insulin-like growth factor 1 [IGF1]) contribute to exercise capacity in healthy men. This issue remains unclear in CHF.Methods and ResultsWe studied 205 men with CHF (age 60 ± 11 years, New York Heart Association [NYHA] Class I/II/III/IV: 37/95/65/8; LVEF [left ventricular ejection fraction]: 31 ± 8%). Exercise capacity was expressed as peak oxygen consumption (peak VO₂), peak O₂ pulse, and ventilatory response to exercise (VE-VCO₂ slope). In multivariable models, reduced peak VO₂ (and reduced peak O₂ pulse) was associated with diminished serum total testosterone (TT) (P < .01) and free testosterone (eFT; estimated from TT and sex hormone globulin levels) (P < .01), which was independent of NYHA Class, plasma N-terminal pro-brain natriuretic peptide, and age. These associations remained significant even after adjustment for an amount of leg lean tissue. In multivariable models, high VE-VCO₂ slope was related to reduced serum IGF1 (P < .05), advanced NYHA Class (P < .05), increased plasma NT-proBNP (P < .0001), and borderline low LVEF (P = .07). In 44 men, reassessed after 2.3 ± 0.4 years, a reduction in peak VO₂ (and peak O₂ pulse) was accompanied by a decrease in TT (P < .01) and eFT (P ≤ .01). Increase in VE-VCO₂ slope was related only to an increase in plasma NT-proBNP (P < .05).ConclusionsIn men with CHF, low circulating testosterone independently relates to exercise intolerance. The greater the reduction of serum TT in the course of disease, the more severe the progression of exercise intolerance. Whether testosterone supplementation would improve exercise capacity in hypogonadal men with CHF requires further studies.     

A 6-month follow-up of intermittent levosimendan administration effect on systolic function, specific activity questionnaire, and arrhythmia in advanced heart failure

BackgroundLevosimendan (LS) improves cardiac contractility without increasing myocardial oxygen demand. We administrated LS on a monthly intermittent 24-hour protocol and evaluated the clinical effect after 6 months in a randomized, open, prospective study.Methods and ResultsFifty patients (age 45–65 years) with LV systolic dysfunction and New York Heart Association (NYHA) III or IV were randomized in 2 groups. LS group (n = 25) was compared with a control group (n = 25) matched for sex, age, and NYHA class. LS was given monthly on a 24-hour intravenous protocol for 6 months. Patients were evaluated by specific activity questionnaire (SAQ) and echocardiography (ECHO) before and 3 to 5 days after last drug administration, whereas 24-hour Holter recording was performed before and during last drug administration. Patients in LS and control group had same baseline SAQ, ECHO, and Holter parameters. At the end of the study, a larger proportion of patients in the levosimendan group reported improvement in symptoms (dyspnea and fatigue) (65% versus 20% in controls, P < .01). After 6 months, the LS group had a significant increase in LV ejection fraction versus controls (28 ± 7 versus 21 ± 4 %, P = .003), LV shortening fraction (15 ± 3 versus 11 ± 3 %, P = .006) and a decrease in mitral regurgitation (1.5 ± 0.8 versus 2.7 ± 0.6, P = .0001). There was no increase in supraventricular or ventricular beats or supraventricular tachycardia and VT episodes in LS group, compared with controls. Two patients from the LS group died in the 6-month follow-up period, compared with 8 patients in the control group (8% versus 32%, P < .05).ConclusionsA 6-month intermittent LS treatment in patients with decompensated advanced heart failure improved symptoms and LV systolic function.     

Prognostic Role of Cardiopulmonary Exercise Testing in Wild-Type Transthyretin Amyloid Cardiomyopathy Patients Treated With Tafamidis

BackgroundThe prognostic value of cardiopulmonary exercise testing (CPET) in patients with wild-type transthyretin cardiac amyloidosis treated with tafamidis is unknown.Methods and ResultsThis retrospective study included patients with wtATTR who underwent baseline cardiopulmonary exercise testing and were treated with tafamidis from August 31, 2018, until March 31, 2020. Univariate logistic and multivariate cox-regression models were used to predict the occurrence of the primary outcome (composite of mortality, heart transplant, and palliative inotrope initiation). A total of 33 patients were included (median age 82 years, interquartile range [IQR] 79–84 years), 84% were Caucasians and 79% were males). Majority of patients had New York Heart Association functional class III disease at baseline (67%). The baseline median peak oxygen consumption (VO₂) and peak circulatory power (CP) were 11.35 mL/kg/min (IQR 8.5–14.2 mL/kg/min) and 1485.8 mm Hg/mL/min (IQR 988–2184 mm Hg/mL/min), respectively, the median ventilatory efficiency was 35.7 (IQR 31–41.2). After 1 year of follow-up, 11 patients experienced a primary end point. Upon multivariate analysis, the low peak VO₂ (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.23–0.79, P = .007], peak CP (HR 0.98, 95% CI 0.98–0.99, P = .02), peak oxygen pulse (HR 0.62, 95% CI 0.39–0.97, P = .03), and exercise duration of less than 5.5 minutes (HR 5.82, 95% CI 1.29–26.2, P = .02) were significantly associated with the primary outcome.ConclusionsTafamidis-treated patients with wtATTR who had baseline low peak VO₂, peak CP, peak O₂ pulse, and exercise duration of less than 5.5 minutes had worse outcomes.     

Impact of atrial fibrillation in heart failure with normal ejection fraction: a clinical and echocardiographic study

BackgroundThe clinical significance of atrial fibrillation (AF) in heart failure with normal ejection fraction (HFNEF) remains undetermined.Methods and ResultsWe compared the clinical and echocardiographic characteristics among 238 patients hospitalized for HF. Using the cutoff of left ventricular EF of 50%, there were 146 patients with HFNEF (AF = 42) and 92 with systolic HF (AF = 30). When compared among HFNEF, the New York Heart Association (NYHA) class (2.61 ± 0.51 versus 2.21 ± 0.46; P < .05), 6-minute walk distance (279.7 ± 66.0 versus 338.0 ± 86.1 m; P < .01), quality of life score (26.1 ± 14.3 versus 19.5 ± 10.3; P < .05), and previous HF hospitalization were significantly worse in the AF group. These variables were significantly better in HFNEF than systolic HF with sinus rhythm, but the differences were not detected among those with AF. Patients with HFNEF and AF were associated with more severe diastolic dysfunction when compared to sinus rhythm. With a median follow-up of 10.5 months, the proportion of HFNEF patients in AF with recurrent HF hospitalization or death was significantly higher than those in sinus rhythm (28.6% versus 10.6%; P < .01). Both AF and restrictive diastolic dysfunction were independent predictors of HF hospitalization or death in HFNEF.ConclusionPatients with HFNEF and AF were associated with more severe diastolic dysfunction and worse clinical outcomes than those in sinus rhythm.     

Chronotropic competence in endurance trained heart transplant recipients: heart rate is not a limiting factor for exercise capacity

Objectives. The purpose of this study was to show that the chronotropic potential of the well trained heart transplant recipient (HTR) does not limit exercise capacity.Background. Chronotropic incompetence is considered to be the main limiting factor of the functional capacity of heart transplant recipients. However, no systematic study had been published on patients who had spontaneously undergone heavy endurance training for several years.Methods. Heart rate (HR) and respiratory gas exchanges (VO₂, VCO₂, VE) were measured in 14 trained HTRs (T-HTRs) during exercise tests on a bicycle, on a treadmill and by Holter electrocardiography during a race.Results. Peak values observed in T-HTRs during the treadmill test were higher than those reached during the bicycle test (VO_2peak:39.8 ± 6.9 vs. 32.5 ± 7.8 ml·kg⁻¹·min⁻¹, p < 0.001; HR_peak: 169 ± 14 vs. 159 ± 16 bpm, p < 0.01). During treadmill exercise VO_2peakand HR_peakvalues observed were very close to the mean predicted VO_2pmaxand HR_pmax. The maximum heart rate during the race (HR_race) was greater than HR_peakvalues during the treadmill test (179 ± 14 vs 169 ± 14 bpm, p < 0.01) and slightly above the mean predicted values (HR_race/HR_pmax× 100 = 101 ± 10%). The treadmill exercise test yields more reliable data than does the bicycle test.Conclusions. Extensive endurance training enables heart transplant recipients to reach physical fitness levels similar to those of normal sedentary subjects; heart rate does not limit their exercise capacity.     

Heart-type fatty acid-binding protein is more sensitive than troponin T to detect the ongoing myocardial damage in chronic heart failure patients

BackgroundHeart-type fatty acid-binding protein (H-FABP) is a small cytosolic protein and released into the circulation when the myocardium is injured. Previous studies have demonstrated that both H-FABP and troponin T (TnT) are detectable in venous blood samples in chronic heart failure (CHF) patients, suggesting the presence of ongoing myocardial damage (OMD). We hypothesized that a cytosolic marker (H-FABP) is more sensitive than a myofibrillar component (TnT) in the detection of OMD in CHF.Methods and ResultsWe measured serum H-FABP and TnT levels in 126 consecutive CHF patients at admission, and patients were followed-up with a mean period of 474 ± 328 days. Cutoff values for H-FABP (4.3 ng/mL) and TnT (0.01 ng/mL) were determined from previous studies. Positive rate of H-FABP was higher than that of TnT in all CHF patients (46% [58/126] versus 26% [33/126], P < .0001), and in severe CHF (New York Heart Association III/IV) patients (69% [34/49] versus 47% [23/49], P = .0121). There were 27 cardiac events during a follow-up period. In patients with cardiac events, H-FABP was more frequently detected than TnT (88% [24/27] versus 44% [12/27], P = .0103). There were 33 patients with positive H-FABP among 93 patients with negative TnT. Those patients had more severe New York Heart Association class, higher levels of brain natriuretic peptide, and higher rates of cardiac events (36% versus 5%, P < .0001) compared with those both H-FABP and TnT were negative. Kaplan-Meier analysis demonstrated that in patients with negative TnT, positive H-FABP group had higher risk for cardiac events than negative H-FABP group (P < .0001). A multivariate analysis with Cox proportional hazard model showed that H-FABP was the only independent predictor of cardiac events (hazard ratio 15.677, P = .0001). The area under the receiver operating characteristic curve was larger for H-FABP than for TnT (0.779 versus 0.581; P = .009), suggesting that H-FABP had greater predictive capacity for cardiac events than TnT.ConclusionsH-FABP was more sensitive to detect OMD and could identify patients at high risk more effectively than TnT.     

Flow-Mediated Dilation Normalization Predicts Outcome in Chronic Heart Failure Patients

BackgroundReduced flow-mediated dilation (FMD) is a known prognostic marker in heart failure (HF), but may be influenced by the brachial artery (BA) diameter. Aiming to adjust for this influence, we normalized FMD (nFMD) by the peak shear rate (PSR) and tested its prognostic power in HF patients.Methods and ResultsBA diameter, FMD, difference in hyperemic versus rest brachial flow velocity (FVD), PSR (FVD/BA), and nFMD (FMD/PSR × 1000) were assessed in 71 HF patients. At follow-up (mean 512 days), 19 HF (27%) reached the combined endpoint (4 heart transplantations [HTs], 1 left ventricle assist device implantation [LVAD], and 14 cardiac deaths [CDs]). With multivariate Cox regression analysis, New York Heart Association functional class ≥III (hazard ratio [HR] 9.36, 95% confidence interval [CI] 2.11–41.4; P = .003), digoxin use (HR 6.36, 95% CI 2.18–18.6; P = .0010), FMD (HR 0.703, 95% CI 0.547–0.904; P = .006), PSR (HR 1.01, 95% CI 1.005–1.022; P = .001), FVD (HR 1.04, 95% CI 1.00–1.06; P = .02), and nFMD (HR 0.535, 95% CI 0.39–0.74; P = .0001) were predictors of unfavorable outcome. Receiver operating characteristic curve for nFMD showed that patients with nFMD >5 seconds had significantly better event-free survival than patients with nFMD ≤5 seconds (log-rank test: P < .0001).ConclusionsnFMD is a strong independent predictor of CD, HT, and LVAD in HF with left ventricular ejection fraction <40%. Patients with nFMD >5 seconds have a better prognosis than those with lower values.     

Is static hyperinflation a limiting factor during exercise in adolescents with cystic fibrosis?

Increased work of breathing is considered to be a limiting factor in patients with cystic fibrosis (CF) performing aerobic exercise. We hypothesized that adolescents with CF and with static hyperinflation are more prone to a ventilatorily limited exercise capacity than non‐static hyperinflated adolescents with CF. Exercise data of 119 adolescents with CF [range 12–18 years], stratified for static hyperinflation, defined as ratio of residual volume to total lung capacity (RV/TLC) > 30%, were obtained during a progressive bicycle ergometer test with gas analysis and analyzed for ventilatory limitation. Static hyperinflation showed a significant, though weak association (Φ 0.38; P < 0.001) with a ventilatorily limited exercise capacity (breathing reserve index at maximal effort >0.70; FEV₁ < 80% predicted and reduced exercise capacity, defined as VO_2peak < 85% predicted). Analysis of association for increasing degrees of hyperinflation showed an increase to Φ 0.49 (P < 0.001) for RV/TLC > 50%. In adolescents with static hyperinflation, peak work rate (W_peak; 3.1 ± 0.7 W/kg (75.1 ± 17.3% of predicted), peak oxygen uptake (VO_2peak/kg (ml/min/kg); 39.2 ± 9.2 ml/min/kg (91.0 ± 20.3% of predicted), peak heart rate (HR_peak; 176 ± 19 beats/min) were significantly (P < 0.05) decreased when compared with non‐static hyperinflated adolescents (W_peak 3.5 ± 0.5 W/kg (81.4 ± 10.0% of predicted)); VO_2peak/kg (ml/min/kg); 43.1 ± 7.5 ml/min/kg (98.0 ± 15.1% of predicted); and HR_peak 185 ± 14 beats/min). Additionally, no difference was found in the degree of association of FEV₁ (%) and RV/TLC (%) with VO_2peak/kg_pred and W_peak/kg_Pred, but we found the RV/TLC (%) to be a slightly stronger predictor of VO_2peak/kg_pred and W_peak/kg_Pred than FEV₁ (%). These results indicate that the presence of static hyperinflation in adolescents with CF by itself does not strongly influence ventilatory constraints during exercise and that static hyperinflation is only a slightly stronger predictor of W_peak/kg_Pred and VO_2peak/kg_Pred than airflow obstruction (FEV₁ (%)). Pediatr. Pulmonol. 2011; 46:119–124. © 2011 Wiley‐Liss, Inc.     

Improved carotid intima-media thickness-induced high-intensity interval training associated with decreased serum levels of Dkk-1 and sclerostin in type 2 diabetes

AimsCarotid intima-media thickness (cIMT) is a validated surrogate marker of atherosclerosis. Dickkopf-1 (Dkk-1) and sclerostin modulate wingless signaling, which is involved in atherosclerosis. The purpose of this study was to investigate whether 12 weeks of high-intensity interval training (HIIT) would improve cIMT and serum Dkk-1 and sclerostin levels in patients with type 2 diabetes.MethodsSeventy-four sedentary patients with type 2 diabetes were randomly divided into HIIT and control groups. The HIIT group intervention was 6 intervals (4 min) at 85%–90% HR_max separated by 3 min at 45%–50% HR_max in 3 sessions/week for 12 weeks. Before and after the intervention, cIMT, artery diameter and wall/lm ratio were recorded with high-resolution ultrasound. Serum sclerostin and Dkk-1 were measured by enzyme-linked immunosorbent assay (ELISA).ResultscIMT decreased significantly in the HIIT group (0.83 ± 0.17 baseline, 0.71 ± 0.14 follow-up) compared to the control group (0.84 ± 0.20 baseline, 0.85 ± 0.19 follow-up) (P < .05). Dkk-1 and sclerostin decreased significantly after 12 weeks of HIIT (P < .01). In addition, VO_2peak was increased in the HIIT group than the control group (by 6.2 mL/kg/min) (P < .05). There was a positive correlation between percent changes in cIMT and percent changes in Dkk-1 and sclerostin (both P < .01). Additionally, there were a negative correlation between percent changes VO2peak and cIMT (r = − 0.740, P = .003), Dkk-1 (r = − 0.844, P < .001) and sclerostin (r = − 0.575, P = .001) in HIIT group.ConclusionOur results indicate that HIIT decreases cIMT, serum levels of Dkk-1 and sclerostin and improves VO_2peak in patients with type 2 diabetes.