Fatigue syndrome in patients with chronic heart failure

The dissertation is devoted to the study of fatigue syndrome in patients with chronic heart failure (CHF). The work considers fatigue not as an isolated symptom but as an independent clinical syndrome that accompanies CHF from its early stages and is related to its severity. The study includes an assessment of the severity of clinical manifestations of fatigue depending on the severity of CHF, an analysis of the morpho-functional state of skeletal musculature, and the development of subjective (visual analogue scale, questionnaire, vocabulary of fatigue) and objective (muscle ultrasonography, tensiometry with a specially designed device, modified six-minute walking test with a pedometer) methods for its diagnosis. Special attention is given to a comparative evaluation of the efficacy of standard CHF therapy and its combination with metabolic agents (preductal and mildronate) for the correction of fatigue syndrome.

The problem of fatigue has remained one of the most topical issues in physiology for several centuries, since one of its main tasks is to study the human organism at the moment of performing work [122]. Fatigue is a natural physiological process; however, pathologically increased fatigability is a frequent symptom of many diseases, including chronic heart failure (CHF). Chronic heart failure is one of the most pressing medical and social problems in the majority of developed countries of the world [80]. Its relevance is aggravated by the steadily growing incidence of CHF and its unfavourable prognosis. Fatigue in this pathology ranks second in frequency after dyspnoea and occurs in 94.3% of cases [58]. However, it attracts little attention from physicians, especially at the early stages of the disease [38]. The fact of the occurrence of increased fatigability in patients with CHF has long been known, but the causes and mechanisms of the development of this phenomenon have not yet been fully elucidated, despite the close attention paid to them in recent years [76]. Both subjective and objective methods of assessing the severity of fatigue as one of the criteria of CHF are lacking. The diagnostic and prognostic value of fatigue as a criterion of heart failure deserves attention. The state of skeletal muscles, which play an important role both in the pathogenesis of fatigue and in the pathogenesis of CHF itself, has been insufficiently studied. The possibilities of therapeutic influence on fatigue in this pathology have not been investigated at all. The study of fatigue in CHF is also of considerable social significance with regard to assessing the severity of the disease, disability, and the development of preventive and rehabilitation measures aimed generally at improving the quality of life of the patient and maintaining his or her working capacity.

The aim of the study is to determine the severity of clinical manifestations of fatigue syndrome in chronic heart failure of varying severity, to develop methods of objective diagnosis, and to evaluate the possibilities of its correction by means of standard therapy and the additional use of metabolic agents.

Objectives:

1. To determine the severity of clinical manifestations of fatigue syndrome depending on the severity of chronic heart failure.

2. To compare morpho-functional changes in skeletal musculature with the severity of CHF and with the clinical manifestations of fatigue syndrome.

3. To develop methods of objective diagnosis of fatigability in CHF.

4. To determine the efficacy of standard therapy and of the additional use of metabolic agents (mildronate and preductal) in the treatment of fatigue syndrome in CHF.

Scientific novelty of the study

On the basis of the data obtained, fatigue in CHF has for the first time been described not as a symptom but as a syndrome. The association of its severity with the severity of the disease has been revealed. The state of skeletal musculature in patients with CHF has been investigated using new objective methods (muscle ultrasonography and tensiometry). For tensiometry, a device entitled "Apparatus for determining the contractile ability of the posterior group of muscles of the leg" has been developed, for which a utility model patent No. 57580 has been obtained. A modified six-minute walking test has been proposed, using an Omron HJ-113-E pedometer. The efficacy of the conventional scheme of therapy and of metabolic agents (preductal and mildronate) for its correction has been evaluated.

Practical significance

It has been shown that fatigue syndrome is also detected at the initial stages of CHF. The necessity of early diagnosis of this syndrome in patients with heart failure has been substantiated. Original methods of individual assessment of fatigue severity (a visual analogue scale and a questionnaire) have been developed, and a vocabulary of fatigue has been compiled, which can be used in diagnosing both fatigue syndrome and the severity of CHF itself. The work presents new methods of objective investigation of peripheral musculature (ultrasonography and tensiometry), which can also be applied for monitoring the state of muscles during treatment. The original method of ultrasonography can be used for assessing the state of muscles in other diseases as well. A modified six-minute walking test has been developed using an Omron HJ-113-E pedometer, which represents an individual means of self-monitoring of exercise tolerance by the patient.

The efficacy of the conventional scheme of CHF treatment and of metabolic agents (preductal and mildronate) for the correction of fatigue syndrome has been demonstrated. On the basis of the data obtained, the use of metabolic agents as symptomatic remedies in addition to the main therapy of CHF has been proposed for the treatment of pronounced fatigue syndrome.

Approbation of the work

The materials of the dissertation were presented and discussed at the First All-Russian Congress of the Society of Specialists in Heart Failure "Heart Failure ' 2004" (Moscow, 2004), as well as at regional scientific and practical conferences of young scientists and specialists (Orenburg, 2004, 2005, 2006, 2008).

Publications

Thirteen scientific works have been published on the topic of the study, and a utility model patent No. 57580 dated 27 October 2006 has been obtained.

Main propositions submitted for defence

1. All manifestations of fatigue in CHF can be combined into a fatigue syndrome, which accompanies it from the earliest stages and is one of the criteria of disease severity in diagnosis and assessment of treatment efficacy.

2. Skeletal muscles in CHF undergo structural and functional remodelling, beginning from the early stages of the disease, when it is of an adaptive character, while at the later stages the process becomes maladaptive.

3. The use of a pedometer in conducting the six-minute walking test does not diminish its diagnostic value and can be introduced into broad practice as a means of monitoring exercise tolerance for its assessment both by the physician and by the patient with CHF himself or herself.

4. Adequate treatment of CHF makes it possible to reduce the severity of fatigue syndrome and to improve exercise tolerance, with metabolic agents (preductal and mildronate) being applicable symptomatically specifically for the correction of this syndrome.

Implementation of the study results into healthcare practice

The data obtained are used in the in-patient department of the Orenburg Regional Clinical Hospital No. 2, as well as in the educational process of the Department of Hospital Therapy named after R.G. Mezhehovsk. An informational letter has been prepared for the dissemination of the results obtained in the Orenburg region.

Structure and volume of the dissertation

The work is presented on 146 pages of computer-typed text and is illustrated with 26 figures and 24 tables. The dissertation consists of an introduction, a literature review, a chapter on observed patients and methods of investigation, two chapters of results of original investigations, a chapter of discussion, conclusions, practical recommendations, and an appendix. The bibliography includes 250 references, of which 107 are by Russian and 143 by foreign authors.