Limited Maximal Exercise Capacity in Patients With Chronic Heart Failure

Esposito, Fabio; Mathieu-Costello, Odile; Shabetai, Ralph; Wagner, Peter D.; Richardson, Russell S.

doi:10.1016/j.jacc.2009.11.086

Cited by 186 publications

(223 citation statements)

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“…Decreased skeletal muscle oxidative capacity (63), secondary to reduced mitochondrial density (12,13) and/or function (10,36,52), may contribute to exercise intolerance, the hallmark symptom of HF. Moreover, as mitochondrial dysfunction is associated with fiber atrophy (7), impaired energetics may reduce physical function by promoting muscle wasting and, in turn, weakness (21).…”

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confidence: 99%

Skeletal muscle mitochondrial density, gene expression, and enzyme activities in human heart failure: minimal effects of the disease and resistance training

Toth

Miller

Ward

et al. 2012

Journal of Applied Physiology

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Toth MJ, Miller MS, Ward KA, Ades PA. Skeletal muscle mitochondrial density, gene expression, and enzyme activities in human heart failure: minimal effects of the disease and resistance training. J Appl Physiol 112: 1864 -1874, 2012. First published March 29, 2012 doi:10.1152/japplphysiol.01591.2011.-Impaired skeletal muscle energetics could adversely affect physical and metabolic function in patients with heart failure (HF). The effect of HF on aspects of mitochondrial structure and function, independent of muscle disuse and other disease-related confounding factors, however, is unclear. Moreover, no study has evaluated whether resistance exercise training, a modality that increases functional capacity, might derive its benefits through modulation of mitochondrial structure and function. Thirteen HF patients and 14 age-and physical activity-matched controls were evaluated for skeletal muscle mitochondrial size/content, gene expression, and enzyme activity before and after an 18-wk resistance exercise-training program. At baseline, HF patients and controls had similar mitochondrial fractional areas, although HF patients had larger average mitochondrion size (P Ͻ 0.05) and a trend toward a reduced number of mitochondria (P Յ 0.10). No differences in the expression of transcriptional regulators or cytochrome oxidase subunits or the activity of mitochondrial and cytosolic enzymes were noted. Relationships among transcriptional regulators suggested that networks controlling mitochondrial content and gene expression are intact. Resistance training increased (P Ͻ 0.01) mitochondrial transcription factor A expression in patients and controls, and this increase was related to improvements in muscle strength (P ϭ 0.05). Training did not, however, alter mitochondrial size/content, enzyme activities, or expression of other transcriptional regulators. In conclusion, our results suggest that the HF syndrome has minimal effects on skeletal muscle mitochondrial biology when the confounding effects of muscle disuse and other disease-related factors are removed. Moreover, the beneficial effects of resistance training on physical function in HF patients and controls are likely not related to alterations in mitochondrial biology. oxidative metabolism; ultrastructure; physical disability IMPAIRED SKELETAL MUSCLE ENERGETICS in heart failure (HF) patients (32) may contribute to physical disability and metabolic dysfunction. Decreased skeletal muscle oxidative capacity (63), secondary to reduced mitochondrial density (12, 13) and/or function (10, 36, 52), may contribute to exercise intolerance, the hallmark symptom of HF. Moreover, as mitochondrial dysfunction is associated with fiber atrophy (7), impaired energetics may reduce physical function by promoting muscle wasting and, in turn, weakness (21). Because mitochondrial dysfunction has been implicated in the pathophysiology of diabetes (41), alterations in mitochondrial content and/or function could also contribute to the high prevalence of insulin resistance in the HF population ...

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Skeletal muscle mitochondrial density, gene expression, and enzyme activities in human heart failure: minimal effects of the disease and resistance training

Toth

Miller

Ward

et al. 2012

Journal of Applied Physiology

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“…Interestingly, NO blockade in healthy muscle also resulted in a off-transient change in Pmv O 2 in a similar fashion to that observed in severe CHF, which implicates a reduction in NO bioavailability as a culprit in the peripheral maladaptations observed in CHF (10). Future interventions such as hyperoxia or antioxidant supplementation that have been demonstrated to increase O 2 supply and reduce free radical associated oxidative stress (2,5,19), respectively, may be useful in improving the transport of O 2 from blood to cell and restoring the exercise capacity in patients with CHF.…”

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“…In keeping with the integrative study of the central and peripheral factors underlying exercise intolerance in patients with CHF, Esposito et al (5) implemented both large (cycle ergometry) and small (single leg-knee extension) muscle mass exercise modalities and created a situation in which patients with CHF exhibited a cardiac reserve despite a failing heart. Altering Q o 2 by breathing 100% O 2 during cycle exercise further revealed a metabolic reserve in patients with CHF; however, this was not apparent during knee-extension exercise since the O 2 delivery per unit of muscle mass was already elevated in this modality compared with cycle ergometry.…”

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confidence: 99%

“…However, the consequences of this failing heart manifest in skeletal muscle and peripheral vasculature. Based on current knowledge, this peripheral dysfunction pertaining to the Q o 2 -to-V O 2 relationship is driven by a reduction in the diffusive ability of O 2 to move from the blood to the myocyte (5). Further investigation of the independent contribution of Q o 2 and V O 2 will likely reveal the mechanisms responsible for the reduced exercise tolerance in CHF and may prove insightful regarding the potential therapeutic targets of pharmacological and nonpharmacological treatments of this disease.…”

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Integrative research: the key to unlocking the mysteries of chronic heart failure and skeletal muscle dysfunction

Trinity

Richardson

2010

American Journal of Physiology-Heart and Circulatory Physiology

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REDUCTIONS IN EXERCISE CAPACITY in patients with chronic heart failure (CHF) were originally linked solely to central limitations associated with a malfunctioning cardiac pump. However, over the last 20 years, peripheral factors related to skeletal muscle and the vascular/skeletal muscle interface have been implicated in this phenomenon. Specifically, muscle atrophy, fiber-type alterations, reduced mitochondrial enzymes, decreased mitochondrial volume density, and decreased capillarity (3,4,9,(12)(13)(14)22) have gained attention since these changes have been associated with CHF. Most certainly, the central and peripheral alterations are intimately linked, requiring an integrative approach to understanding the limitations and mechanisms responsible for the diminished work capacity in this patient population.In this issue of the American Journal of Physiology-Heart and Circulatory Physiology, Copp et al.(1) employed an integrative approach to examine peripheral dysfunction in CHF as measured by the off-transient or recovery kinetics of microvascular O 2 pressure (Pmv O 2 ) and coupled this peripheral measure with central hemodynamic and morphological indexes of heart failure. The most novel and important findings of this study were that 1) progressive CHF increasingly slowed the recovery of Pmv O 2 in a mixed fiber-type muscle, 2) mean response time of the off-transient (MRT off ) and the MRT off-on differences (a measure of the asymmetry between on-and off-transients) correlated with central hemodynamic and morphological indexes of heart failure, and 3) off-transient differences may be present despite a lack of on-transient alterations. A recognized limitation of this study is the finding that the correlations of off-transient and central indexes of cardiac failure were likely driven by the inclusion of four animals with the most severe heart failure; this group could be increased in number to solidify these conclusions. Despite this concern regarding the relatively small cohort of severe CHF in the study of Copp et al. (1), these findings have potential importance in terms of functional capacity and may provide insight into why work and exercise tolerance as well as the ability to perform activities of daily living are reduced in patients with CHF.The technique of phosphorescence quenching (20), as used by Copp et al. (1), allowed the direct determination of Pmv O 2 during the transition from exercise to rest in the muscle of mixed fiber type (spinotrapezius). The spinotrapezius was chosen since the muscle fiber-type composition and oxidative capacity are similar to the human quadriceps (21), thereby making this model a relevant and potentially translational animal model. Pmv O 2 is determined by the relationship of delivery and uptake of O 2 (Q o 2 to V O 2 ), which in turn facilitates blood-to-tissue O 2 flux and has an impact on the regulation of cellular metabolism (6,15,17 (1), in the muscle of rats with CHF likely interferes with the ability to recover from muscular contractions, thereby accelerating fati...

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“…8 Significant concern will be maintain on describing the mechanisms essential to enhance the threats regarding reduce functional capacity in patients with Heart failure. 9 A lot of previous studies have defined the basic physiological pattern in patients with reduced ejection fraction with heart failure. 10 In this study, we are trying to summarize the present fundamental clinical features of heart failure leading to adverse condition of patients in presence of proper treatment and plan of care.…”

Section: Discussionmentioning

confidence: 99%

Heart Failure

Ilyas

Zafar

Amin³

2018

TPMJ

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ABSTRACT… Objectives:To observe the function of left ventricular contractile and its pairing with failure preserved ejection fraction. Study Design: Observational longitudinal study. Setting: Punjab institute of Cardiology. Period: Jan 2017 to June 2017. Methods: Four Hundred twenty one Heart failure patients (mean age 51 ± 7 years, 56% females, left ventricular ejection fraction 55±5%) undergo Left ventricular investigation through echocardiography and left heart catheterization of 191 patients. Through tricuspid annular plane systolic excursion (TAPSE), Patients were sorting out and data collect. Mean TAPSE score were 15.03±4.06 cm without any gender differences. Body surface presents strong relation with TAPSE values (r=0.74). Many different pattern consistently found within same patients leading to heart failure, but patients with HFpEFin which each component is operative behave differently. Results: Transformation of different evidences in clinical practice needs proper level of proofs regarding evidences. Out of four hundred twenty one heart failure patients, patients with prolonged heart failure symptoms and high rate of ejection fraction due to adaptive changes by the human body, whereas patients with aggressive mode of work have high mortality ratio. Out of all physiological derangements were strongly link with the TAPSE. Different biomarker-based strategies are much required to implement for excellent patient outcome in heart diseases. Conclusion: Using most common clinical features, we listed four major features with mark differences acts in remodeling and maintain in heart failure. Patients with decreases ejection fraction have more advanced heart failure. Therapeutic treatment specifically targeting main components of heart failure have better pathophysiological changes in less time. HFpEF patients are more chances to develop adaptive cardiac changes.

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Limited Maximal Exercise Capacity in Patients With Chronic Heart Failure

Cited by 186 publications

References 34 publications

Skeletal muscle mitochondrial density, gene expression, and enzyme activities in human heart failure: minimal effects of the disease and resistance training

Skeletal muscle mitochondrial density, gene expression, and enzyme activities in human heart failure: minimal effects of the disease and resistance training

Integrative research: the key to unlocking the mysteries of chronic heart failure and skeletal muscle dysfunction

Heart Failure

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