A Systematic Review of Exercise Interventions in Patients With Heart Failure

Abstract-The clinical efficacy of exercise training in individuals with heart failure is well established, but the mechanism underlying such efficacy has remained unclear. An imbalance between cardiac hypertrophy and angiogenesis is implicated in the transition to heart failure. We investigated the effects of exercise training on cardiac pathophysiology in hypertensive rats. Dahl salt-sensitive rats fed a high-salt diet from 6 weeks of age were assigned to sedentary or exercise (swimming)-trained groups at 9 weeks. Exercise training attenuated the development of heart failure and increased survival, without affecting blood pressure, at 18 weeks. It also attenuated left ventricular concentricity without a reduction in left ventricular mass or impairment of cardiac function. Interstitial fibrosis was increased and myocardial capillary density was decreased in the heart of sedentary rats, and these effects were attenuated by exercise. Exercise potentiated increases in the phosphorylation of Akt and mammalian target of rapamycin observed in the heart of sedentary rats, whereas it inhibited the downregulation of proangiogenic gene expression apparent in these animals. The abundance of the p110␣ isoform of phosphatidylinositol 3-kinase was decreased, whereas those of the p110␥ isoform of phosphatidylinositol 3-kinase and the phosphorylation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase were increased, in the heart of sedentary rats, and all of these effects were prevented by exercise. Thus, exercise training had a beneficial effect on cardiac remodeling and attenuated heart failure in hypertensive rats, with these effects likely being attributable to the attenuation of left ventricular concentricity and restoration of coronary angiogenesis through activation of phosphatidylinositol 3-kinase ( Key Words: hypertension Ⅲ sodium-dependent Ⅲ heart failure Ⅲ exercise Ⅲ hypertrophy Ⅲ rats Ⅲ Dahl Ⅲ coronary angiogenesis .H eart failure is a final common consequence of various forms of heart disease and is a leading cause of mortality worldwide. Cardiac hypertrophy associated with pathological conditions such as hypertension, myocardial infarction, and valvular heart disease has been thought to be an adaptive response to increased external load, given that it can result in normalization of the increase in wall stress induced by mechanical overload. However, increased cardiac mass is also associated with increased morbidity and mortality, 1 with sustained overload eventually leading to heart failure.The serine-threonine protein kinase Akt is an important mediator of phosphatidylinositol 3-kinase (PI3K) signaling and regulates multiple cellular functions. 2 PI3K-Akt signaling is implicated in the regulation of cardiac growth, contractile function, and coronary angiogenesis. [3][4][5] A mismatch between the number of coronary capillaries and the size of cardiomyocytes, resulting in myocardial hypoxia, is thought to develop during the progression of cardiac hypertrophy. 6 Indeed, studies have in...

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“…38 Exercise regimens must, therefore, be carefully calibrated for clinical application to heart failure. 39 …”

Section: Discussionmentioning

confidence: 99%

Exercise Training Alters Left Ventricular Geometry and Attenuates Heart Failure in Dahl Salt-Sensitive Hypertensive Rats

et al. 2009

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“…In addition, endothelial dysfunction is also associated with an increased risk for mortality in HF patients with reduced ejection fraction (HRrEF) <40% [1–3]. A growing body of evidence suggests exercise training improves exercise intolerance and endothelial dysfunction for patients with HFrEF [4–10]. Flow-mediated dilation (FMD) is a well-established measure of assessing endothelial function [11,12].…”

Section: Introductionmentioning

confidence: 99%

Effects of Exercise Interventions on Peripheral Vascular Endothelial Vasoreactivity in Patients with Heart Failure with Reduced Ejection Fraction

Vuckovic

Piano

Phillips

2013

Heart, Lung and Circulation

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Changes in vascular function, such as endothelial dysfunction are linked to the progression of heart failure (HF) and poorer outcomes, such as increased hospitalisations. Exercise training may positively influence endothelial function in HF patients with reduced ejection fraction. The aim of this manuscript is to summarise HF studies evaluating the influence of exercise training on endothelial function as measured by flow mediated vasodilation as a primary outcome and to provide recommendations for future research studies designed to improve peripheral vascular function in HF. Databases were searched for studies published between 1995 and December 2011. Two reviewers determined eligibility and extracted information on study characteristics and quality, exercise interventions, and endothelial function. Eleven articles (N = 318 HF participants with an ejection fraction <40%) were eligible for full review. Aerobic, resistance, or combined exercise training improved endothelium-dependent vasodilation as measured by ultrasound or plethysmography. There is less evidence supporting improvement in endothelium-independent function with exercise training. Sample sizes were small and predominantly male. Future research is needed to address the best mode and optimal dose of exercise for all patients with HF including women and subgroups with specific co-morbidities.

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“…According to a systematic review of randomized controlled trials, exercise might slow the pathophysiological progression of HF. In chronic HF, regular exercise inhibits neurohormonal stimulation and the production of proinflammatory cytokines, reduces levels of natriuretic peptides and systemic vascular resistance, and attenuates the oxidative burden . These favourable effects parallel improvement in symptoms, exercise capacity, and quality of life, while patients who do not improve their exercise capacity significantly after an exercise training programme have a poorer prognosis.…”

Section: Exercise and Endothelial Dysfunction In Heart Failurementioning

confidence: 99%

A contemporary view on endothelial function in heart failure

Shantsila

Wrigley

Blann

et al. 2012

European J of Heart Fail

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The assessment of different aspects of endothelial dysfunction in cardiovascular medicine in general and in heart failure (HF) has been the focus of intense research, and includes vasomotor, haemostatic, antioxidant, and inflammatory activities. Differences also exist in the pattern of endothelial dysfunction depending on aetiology, severity, and stability of HF in individual patients. In the majority of patients with ischaemic aetiology of HF, endothelial dysfunction is systemic in its nature and involves both arteries and veins, conductance vessels and microvascular beds, coronary, pulmonary, and peripheral vessels. The pattern of endothelial dysfunction is more heterogeneous in non-ischaemic HF, with fewer features of systemic abnormalities. Indeed, many subjects with non-ischaemic HF have a functionally preserved endothelium in peripheral arteries, with endothelial dysfunction seen only in coronary vessels. Endothelial dysfunction has significant prognostic value in HF, but its clinical application is hampered by methodological limitations in its assessment. Various medications (including angiotensin-converting enzyme inhibitors and statins) and regular physical activity have been shown to improve endothelial function in HF. However, there are still no pharmaceutical agents specifically targeting the vascular endothelium. Despite the large number of studies, the pathophysiological role of the vascular endothelium and its clinical potential as a therapeutic target has not yet been sufficiently developed and undoubtedly awaits further exploration.--

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A Systematic Review of Exercise Interventions in Patients With Heart Failure

Cited by 14 publications

References 88 publications

Exercise Training Alters Left Ventricular Geometry and Attenuates Heart Failure in Dahl Salt-Sensitive Hypertensive Rats

Exercise Training Alters Left Ventricular Geometry and Attenuates Heart Failure in Dahl Salt-Sensitive Hypertensive Rats

Effects of Exercise Interventions on Peripheral Vascular Endothelial Vasoreactivity in Patients with Heart Failure with Reduced Ejection Fraction

A contemporary view on endothelial function in heart failure

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