Functional Changes of the Myocardium in Patients with Coronary Artery Disease and Paroxysmal Atrial Fibrillation and the Possibilities for Their Correction

The dissertation is devoted to the study of functional changes of the myocardium in patients with coronary artery disease complicated by the paroxysmal form of atrial fibrillation and to the substantiation of possible directions for correction of these changes. The research correlates the clinical features of the course of coronary artery disease with the structural and functional changes of the myocardium assessed by echocardiography, stress echocardiography with tissue Doppler imaging, 24-hour ECG monitoring, exercise tests, perfusion scintigraphy and coronary angiography, and with the characteristics of arrhythmogenic activity. On the basis of a comprehensive clinical and instrumental examination, the pathogenetic factors contributing to the occurrence of paroxysms of atrial fibrillation in coronary artery disease patients are analysed, and the effect of therapy with the angiotensin-converting enzyme inhibitor enalapril on arrhythmogenic activity and parameters of intracardiac haemodynamics is evaluated. The results obtained are intended to improve diagnosis and to refine the therapeutic and prophylactic measures in this category of patients.

Relevance of the research

Among all cardiac rhythm disturbances, paroxysmal atrial fibrillation currently ranks second in frequency of occurrence after extrasystole. This, together with the presence of a large number of life-threatening complications that often lead to persistent loss of working capacity in patients, accounts for the considerable interest in the problem of the aetiology, pathogenesis and treatment tactics of this type of arrhythmia (Kushakovskiy M.S., 1998; Ardashev V.N., 1998). Given that in the Russian Federation there is no unified approach to understanding the role of various aetiological factors in the genesis of paroxysms of atrial fibrillation, in the assessment of the condition and life prognosis of patients, and that clear standards for differential diagnosis and treatment of patients have not been defined, this problem acquires particular significance. The considerable economic expenditures of the state directed at the treatment of these patients give the problem not only medical but also substantial socio-economic importance (Egorov D.F., 1995; Bokeria L.A., 1999).

All disturbances of cardiac rhythm and conduction are symptoms of various pathological processes taking place in the cardiac muscle, which have different significance both in the clinical picture and in the treatment tactics of atrial fibrillation, as well as in the long-term prognosis for each patient. In some cases, paroxysms of AF may be the only symptoms reflecting damage to the cardiac muscle, while in other cases they may complement the clinical picture of the disease. It should be added that this type of cardiac rhythm disturbance may reflect not only myocardial damage but may also result from disturbances of neurohumoral regulation of cardiac activity, various electrolyte disorders and toxic effects on the myocardium (Grishkin Yu.N., 1993). An idiopathic form of atrial fibrillation is also distinguished, when its development cannot be proved by the presence of any pathological process or such processes cannot be identified by available diagnostic means.

Special concern is caused by the frequent assessment by practising physicians of AF as a banal pathology that does not require close attention and targeted treatment of the underlying aetiological cause, which includes a broad group of myocardial diseases. The existence of diverse and sometimes mutually contradictory approaches to the treatment of atrial fibrillation gives rise to the prescription of incorrect therapy and inappropriate treatment tactics in such patients (Revishvili A.Sh., 1990). All of the above explains the need for further research in this area aimed at the most detailed study of aetiological factors, pathogenetic mechanisms and triggering factors, and at the development of a unified approach to the diagnosis and treatment of this category of patients.

At present, the study of the mechanisms of onset and progression of atrial fibrillation is the subject of numerous investigations. The electrophysiological mechanisms of AF development have been covered in sufficient detail in the modern literature (Kushakovskiy M.S., 1998; Zipes D.P., 1988). Many works carried out over the last decade have been devoted to the investigation of diverse biophysical alterations of the cardiac conduction system, which became possible through the introduction into practice of endocardial electrophysiological studies (Bokeria L.A., 1995; Waldo A.L., 1995; Singh B.N., 1993). However, in our opinion, many of these unquestionably fundamental works are excessively abstract and theoretical in character, are not always applicable to practical activity, and do not fully take into account the influence of the entire spectrum of clinical and morphological features of the immediate aetiological cause that led to the generation of a paroxysm of atrial fibrillation. In this context, a direct comparison of the multiple aetiopathogenetic causes with the clinical picture and arrhythmogenic activity will provide an opportunity to develop new directions in the treatment of this type of cardiac rhythm disturbance.

Numerous published data show that the group of patients with atrial fibrillation is highly heterogeneous, and that the triggering mechanisms of the arrhythmia include both morphological and neurohumoral and electrophysiological changes of the myocardium. The group of diseases that may cause the development of paroxysms comprises coronary artery disease, myocarditis, thyrotoxicosis, rheumatic disease, cardiomyopathy and others. A connection is often drawn between the severity of morphological changes of the myocardium and the possibility of arrhythmia occurring (Chireykin L.V., 1996; Egorov D.F., 1997). Such an approach appears to us to be rather simplistic, since with an identical degree of myocardial damage some patients develop paroxysmal atrial fibrillation while in others the disease proceeds without rhythm disorders. Apparently, the relationship between myocardial damage and the occurrence of arrhythmia is of a more complex and multiform character. Thus, for example, in addition to the factors already studied, a certain role in the genesis of cardiac rhythm disturbances is assigned in some recently published works to the inflammatory factor. The greatest number of investigations has been carried out in the study of coronary artery disease (CAD), which is most frequently encountered in patients with paroxysmal atrial fibrillation. There are suggestions that disturbances of cardiac rhythm may serve as an indicator of exacerbation, progression or even of the «debut» of CAD in clinical terms.

Thus, the published data and the accumulated experience of our own clinical observations indicate that the group of CAD patients with cardiac rhythm disturbances of the paroxysmal atrial fibrillation type is not uniform, and that during examination and determination of treatment tactics for these patients all aspects of arrhythmogenesis must be taken into account.

Aim of the study:

To investigate the relationship between the clinical course of coronary artery disease, the structural and functional changes of the myocardium, and the arrhythmogenic activity in patients with the paroxysmal form of atrial fibrillation, and to outline possible avenues for the treatment and prevention of this type of arrhythmia.

Objectives of the study:

1. On the basis of a comprehensive examination of CAD patients, to determine the main and additional pathological factors contributing to the occurrence of paroxysmal atrial fibrillation.

2. To identify features of the clinical course of CAD in patients without cardiac rhythm disturbances and in those with PAF.

3. To determine the structural and functional changes of the myocardium (according to stress echocardiography) in patients suffering from CAD with paroxysmal atrial fibrillation.

4. Using coronary angiography and single-photon emission computed tomography of the heart, to assess the character and severity of atherosclerotic lesions of the coronary arteries in CAD patients with PAF.

5. To determine the optimal scheme of patient examination that would improve the effectiveness of treatment and prevention of atrial fibrillation in CAD patients.

Scientific novelty.

The scientific novelty of the work is determined by the identification of new facts supplementing the existing concepts regarding the causes of rhythm and conduction disturbances in CAD patients.

The main pathogenetic factors determining electrical instability of the myocardium in persons with coronary myocardial damage have been identified.

For the first time, a relationship has been revealed between changes in arrhythmogenic activity and different degrees of severity of structural and functional myocardial changes.

For the first time, the roles of chronic and transient myocardial ischaemia in the genesis of arrhythmic events have been assessed.

For the first time, features of coronary blood flow both at rest and under load have been assessed during myocardial SPECT and coronary angiography. The absence of a clear relationship between the localisation of atherosclerotic lesions of the coronary arteries and the electrical instability of the atria has been demonstrated.

Practical significance.

The totality of the parameters determined during the comprehensive examination of CAD patients makes it possible to obtain the most complete picture of the structural and functional changes of the myocardium that lead to the generation of paroxysms of atrial fibrillation.

The leading factors have been identified, knowledge of which enables practising cardiologists to adequately assess the risk of cardiac rhythm disturbances, with account taken of the possible mechanisms of their induction, and to decide on the need to correct the proarrhythmic components of CAD.

The main parameters characterising disturbances of cardiac electrical activity in coronary myocardial damage have been presented; their significance in the clinical picture of the disease has been determined; and the diagnostic capabilities of functional methods of examination of CAD patients with PAF have been refined.

The significance of the results of stress echocardiography in the prognosis of arrhythmic events and in the choice of treatment method for patients suffering from CAD with paroxysmal atrial fibrillation has been assessed.

Data have been obtained on the absence of a significant relationship between transient myocardial ischaemia, the severity of coronary insufficiency, and the presence and frequency of AF paroxysms.

The contribution of structural and functional changes of the myocardium to arrhythmogenesis has been demonstrated, which determines the need for therapeutic measures aimed at eliminating these shifts.

The necessity of pharmacological correction of the main pathological changes that contribute to the occurrence and progression of arrhythmic complications of CAD has been demonstrated. The possibilities of preventing PAF with the aid of medicinal agents that are not specific antiarrhythmic drugs but act upon the main links of the cardiovascular continuum have been determined.

Main propositions put forward for defence:

1. Paroxysmal atrial fibrillation in CAD patients results from the combined action of such factors as chronic myocardial ischaemia, the formation and progression of cardiosclerosis, an imbalance of the autonomic nervous system, and anatomical and electrophysiological remodelling of the myocardium.

2. The performance of a set of diagnostic procedures, including 24-hour ECG monitoring, echocardiography and stress echocardiography with low-dose dobutamine supplemented by tissue Doppler imaging, and exercise tests, makes it possible to obtain the most complete information on the structural and functional changes of the myocardium and to select the most optimal scheme of therapy for this category of patients.

3. The inclusion of angiotensin-converting enzyme inhibitors in the scheme of therapy of CAD patients with PAF, regardless of the degree of severity of heart failure and the level of arterial pressure, improves the arrhythmic prognosis of this category of patients.