Exercise intolerance is the primary chronic symptom in heart failure with preserved ejection fraction (HFpEF), the most common form of heart failure in older patients; however its pathophysiology is ...not well understood. Recent data suggest that peripheral factors such as skeletal muscle (SM) dysfunction may be important contributors. Therefore, 38 participants, 23 patients with HFpEF (69 ± 7 years) and 15 age-matched healthy controls (HCs), underwent magnetic resonance imaging and cardiopulmonary exercise testing to assess for SM, intermuscular fat (IMF), subcutaneous fat, total thigh, and thigh compartment (TC) areas and peak exercise oxygen consumption (peak VO2 ). There were no significant intergroup differences in total thigh area, TC, subcutaneous fat, or SM. However, in the HFpEF versus HC group, IMF area (35.6 ± 11.5 vs 22.3 ± 7.6 cm2 , p = 0.01), percent IMF/TC (26 ± 5 vs 20 ± 5%, p = 0.005), and the ratio of IMF/SM (0.38 ± 0.10 vs 0.28 ± 0.09, p = 0.007) were significantly increased, whereas percent SM/TC was significantly reduced (70 ± 5 vs 75 ± 5, p = 0.009). In multivariate analyses, IMF area (partial r = −0.51, p = 0.002) and IMF/SM ratio (partial r = −0.45, p = 0.006) were independent predictors of peak VO2 whereas SM area was not (partial r = −0.14, p = 0.43). Thus, older patients with HFpEF have greater thigh IMF and IMF/SM ratio compared with HCs, and these are significantly related to their severely reduced peak VO2 . These data suggest that abnormalities in SM composition may contribute to the severely reduced exercise capacity in older patients with HFpEF. This implicates potential targets for novel therapeutic strategies in this common debilitating disorder of older persons.
Abstract Objectives The aim of this study was to examine skeletal muscle mitochondria content, oxidative capacity, and the expression of key mitochondrial dynamics proteins in patients with heart ...failure with preserved ejection fraction (HFpEF), as well as to determine potential relationships with measures of exercise performance. Background Multiple lines of evidence indicate that severely reduced peak exercise oxygen uptake (peak VO2 ) in older patients with HFpEF is related to abnormal skeletal muscle oxygen utilization. Mitochondria are key regulators of skeletal muscle metabolism; however, little is known about how these organelles are affected in HFpEF. Methods Both vastus lateralis skeletal muscle citrate synthase activity and the expression of porin and regulators of mitochondrial fusion were examined in older patients with HFpEF (n = 20) and healthy, age-matched control subjects (n = 17). Results Compared with age-matched healthy control subjects, mitochondrial content assessed by porin expression was 46% lower (p = 0.01), citrate synthase activity was 29% lower (p = 0.01), and Mfn2 (mitofusin 2) expression was 54% lower (p <0.001) in patients with HFpEF. Expression of porin was significantly positively correlated with both peak VO2 and 6-min walk distance (r = 0.48, p = 0.003 and r = 0.33, p = 0.05, respectively). Expression of Mfn2 was also significantly positively correlated with both peak VO2 and 6-min walk distance (r = 0.40, p = 0.02 and r = 0.37, p = 0.03 respectively). Conclusions These findings suggest that skeletal muscle oxidative capacity, mitochondrial content, and mitochondrial fusion are abnormal in older patients with HFpEF and might contribute to their severe exercise intolerance.
Objectives The purpose of this study was to evaluate the mechanisms for improved exercise capacity after endurance exercise training (ET) in elderly patients with heart failure and preserved ejection ...fraction (HFPEF). Background Exercise intolerance, measured objectively by reduced peak oxygen consumption (VO2 ), is the primary chronic symptom in HFPEF and is improved by ET. However, the mechanisms are unknown. Methods Forty stable, compensated HFPEF outpatients (mean age 69 ± 6 years) were examined at baseline and after 4 months of ET (n = 22) or attention control (n = 18). The VO2 and its determinants were assessed during rest and peak upright cycle exercise. Results After ET, peak VO2 in those patients was higher than in control patients (16.3 ± 2.6 ml/kg/min vs. 13.1 ± 3.4 ml/kg/min; p = 0.002). That was associated with higher peak heart rate (139 ± 16 beats/min vs. 131 ± 20 beats/min; p = 0.03), but no difference in peak end-diastolic volume (77 ± 18 ml vs. 77 ± 17 ml; p = 0.51), stroke volume (48 ± 9 ml vs. 46 ± 9 ml; p = 0.83), or cardiac output (6.6 ± 1.3 l/min vs. 5.9 ± 1.5 l/min; p = 0.32). However, estimated peak arterial-venous oxygen difference was significantly higher in ET patients (19.8 ± 4.0 ml/dl vs. 17.3 ± 3.7 ml/dl; p = 0.03). The effect of ET on cardiac output was responsible for only 16% of the improvement in peak VO2. Conclusions In elderly stable compensated HFPEF patients, peak arterial-venous oxygen difference was higher after ET and was the primary contributor to improved peak VO2 . This finding suggests that peripheral mechanisms (improved microvascular and/or skeletal muscle function) contribute to the improved exercise capacity after ET in HFPEF. (Prospective Aerobic Reconditioning Intervention Study PARIS; NCT01113840 )
Objectives The purpose of this study was to determine the mechanisms responsible for reduced aerobic capacity (peak V o2 ) in patients with heart failure with preserved ejection fraction (HFPEF). ...Background HFPEF is the predominant form of heart failure in older persons. Exercise intolerance is the primary symptom among patients with HFPEF and a major determinant of reduced quality of life. In contrast to patients with heart failure and reduced ejection fraction, the mechanism of exercise intolerance in HFPEF is less well understood. Methods Left ventricular volumes (2-dimensional echocardiography), cardiac output, V o2 , and calculated arterial-venous oxygen content difference (A-V o2 Diff) were measured at rest and during incremental, exhaustive upright cycle exercise in 48 HFPEF patients (age 69 ± 6 years) and 25 healthy age-matched controls. Results In HFPEF patients compared with healthy controls, V o2 was reduced at peak exercise (14.3 ± 0.5 ml·kg·min−1 vs. 20.4 ± 0.6 ml·kg·min−1 ; p < 0.0001) and was associated with a reduced peak cardiac output (6.3 ± 0.2 l·min−1 vs. 7.6 ± 0.2 l·min−1 ; p < 0.0001) and A-V o2 Diff (17 ± 0.4 ml·dl−1 vs. 19 ± 0.4 ml·dl−1 , p < 0.0007). The strongest independent predictor of peak V o2 was the change in A-V o2 Diff from rest to peak exercise (A-V o2 Diff reserve) for both HFPEF patients (partial correlate, 0.58; standardized β coefficient, 0.66; p = 0.0002) and healthy controls (partial correlate, 0.61; standardized β coefficient, 0.41; p = 0.005). Conclusions Both reduced cardiac output and A-V o2 Diff contribute significantly to the severe exercise intolerance in elderly HFPEF patients. The finding that A-V o2 Diff reserve is an independent predictor of peak V o2 suggests that peripheral, noncardiac factors are important contributors to exercise intolerance in these patients.
It is unknown if vigorous to maximal aerobic interval training (INT) is more effective than traditionally prescribed moderate-intensity continuous aerobic training (MCT) for improving peak oxygen ...uptake (V o2 ) and the left ventricular ejection fraction (LVEF) in patients with heart failure with reduced ejection fraction. MEDLINE, PubMed, Scopus, and the Web of Science were searched using the following keywords: “heart failure,” high-intensity interval exercise,” “high-intensity interval training,” “aerobic interval training,” and “high-intensity aerobic interval training.” Seven randomized trials were identified comparing the effects of INT and MCT on peak V o2 , 5 of which measured the LVEF at rest. The trials included clinically stable patients with heart failure with reduced ejection fraction with impaired left ventricular systolic function (mean LVEF 32%) who were relatively young (mean age 61 years) and predominantly men (82%). Weighted mean differences were calculated using a random-effects model. INT led to significantly higher increases in peak V o2 compared with MCT (INT vs MCT, weighted mean difference 2.14 ml O2 /kg/min, 95% confidence interval 0.66 to 3.63). Comparison of the effects of INT and MCT on the LVEF at rest was inconclusive (INT vs MCT, weighted mean difference 3.29%, 95% confidence interval −0.7% to 7.28%). In conclusion, in clinically stable patients with heart failure with reduced ejection fraction, INT is more effective than MCT for improving peak V o2 but not the LVEF at rest.
Early Breast Cancer Therapy and Cardiovascular Injury Jones, Lee W., PhD; Haykowsky, Mark J., PhD; Swartz, Jonas J., BS ...
Journal of the American College of Cardiology,
10/2007, Letnik:
50, Številka:
15
Journal Article
Recenzirano
Odprti dostop
Early Breast Cancer Therapy and Cardiovascular Injury Lee W. Jones, Mark J. Haykowsky, Jonas J. Swartz, Pamela S. Douglas, John R. Mackey Although recent advances in curative-intent therapies are ...beginning to produce significant survival gains in early breast cancer, these improvements may ultimately be attenuated by increased risk of long-term cardiovascular mortality. This report reviews emerging evidence on the cardiovascular effects of breast cancer adjuvant therapy and proposes a new entity that we have labeled the “multiple-hit” hypothesis. The evidence that lifestyle modification, especially exercise therapy, may mitigate these adverse effects is also reviewed. These issues are of considerable practical importance for cardiovascular clinicians, as identification and intervention in those at high risk for cardiovascular complications may reduce a major cause of mortality in women with early breast cancer.
Cancer and cardiovascular disease (CVD) are leading causes of morbidity and mortality in the United States. Vascular endothelial dysfunction, an important contributor in the development of CVD, ...improves with exercise training in patients with CVD. However, the role of regular exercise to improve vascular function in cancer survivors remains equivocal. We performed a meta-analysis to determine the effect of exercise training on vascular endothelial function in cancer survivors. We searched PubMed (1975 to 2016), EMBASE CINAHL (1937 to 2016), OVID MEDLINE (1948 to 2016), and Cochrane Central Registry of Controlled Trials (1991 to 2016) using search terms: vascular function, endothelial function, flow-mediated dilation FMD, reactive hyperemia, exercise, and cancer. Studies selected were randomized controlled trials of exercise training on vascular endothelial function in cancer survivors. We calculated pooled effect sizes and performed a meta-analysis. We identified 4 randomized controlled trials (breast cancer, n=2; prostate cancer, n=2) measuring vascular endothelial function by FMD (n=3) or reactive hyperemia index (n=1), including 163 cancer survivors (exercise training, n=82; control, n=81). Aerobic exercise training improved vascular function (n=4 studies; standardized mean difference 95% CI=0.65 0.33, 0.96, I2=0%; FMD, weighted mean difference WMD=1.28 0.22, 2.34, I2=23.2%) and peak exercise oxygen uptake (3 trials; WMD 95% CI=2.22 0.83, 3.61 mL/kg/min; I2=0%). Our findings indicate that exercise training improves vascular endothelial function and exercise capacity in breast and prostate cancer survivors.
Abstract The primary chronic symptom in patients with clinically stable heart failure (HF) is reduced exercise tolerance, measured as decreased peak aerobic power (peak oxygen consumption V o2 ), and ...is associated with reduced quality of life and survival. Exercise-based cardiac rehabilitation (EBCR) is a safe and effective intervention to improve peak V o2 , muscle strength, physical functional performance, and quality of life and is associated with a reduction in overall and HF-specific hospitalization in clinically stable patients with HF. Despite these salient benefits, fewer than one-tenth of eligible patients with HF are referred for EBCR after hospitalization. In this review, selection for and timing of EBCR for patients with HF, as well as exercise prescription guidelines with special emphasis on the optimal exercise training intensity to improve peak Vo2 , are discussed.
Recent advances in the pathophysiology of exercise intolerance in patients with heart failure with preserved ejection fraction (HFPEF) suggest that noncardiac peripheral factors contribute to the ...reduced peak V(o2) (peak exercise oxygen uptake) and to its improvement after endurance exercise training. A greater understanding of the peripheral skeletal muscle vascular adaptations that occur with physical conditioning may allow for tailored exercise rehabilitation programs. The identification of specific mechanisms that improve whole body and peripheral skeletal muscle oxygen uptake could establish potential therapeutic targets for medical therapies and a means to follow therapeutic response.
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