Clinical and instrumental features of coronary heart disease in patients without haemodynamically significant coronary artery stenoses

The dissertation is devoted to the study of clinical and instrumental features of coronary heart disease in patients in whom coronary angiography does not reveal haemodynamically significant coronary artery stenoses. It addresses the problem of coronary syndrome X (microvascular angina), the pathogenetic mechanisms of which remain a subject of debate, as well as the issues of differential diagnosis using non-invasive methods. Particular attention is paid to the capabilities of stress echocardiography in detecting myocardial ischaemia and in refining the indications for referring patients to invasive examination.

Relevance of the work. In Russia, almost 15 million people suffer from cardiovascular diseases every year, and in the mortality structure the share of this pathology exceeds 55% (Bokeriya L.A. et al., 1999; Tozhiev M.S. et al., 2000; Oteva E.A. et al., 2002). In recent years a tendency towards an increase in cardiovascular pathology has been observed.

Attention to the problems of coronary heart disease (CHD) and its insufficiently studied forms is justified not only by the leading place of CHD in the morbidity and mortality structure of the population. CHD also leads to disability and substantially reduces the quality of life.

The study of the state of the coronary bed in CHD patients is of great importance for diagnosis and for the development of treatment approaches. At present, coronary angiography (CAG) is the most widely used method, the so-called "gold standard". Despite its clear diagnostic advantages, this invasive diagnostic method is justified only in stenosing atherosclerotic lesions of the coronary arteries, when CAG can be combined with angioplasty and stenting and with the planning of coronary artery bypass surgery. For patients with intact coronary arteries, CAG is an expensive and of little benefit procedure. At first glance, modern non-invasive diagnostic methods simplify the problem of diagnosing CHD and allow an accurate diagnosis to be made in most cases. In practice, however, the situation is different. Failure to follow clear diagnostic algorithms for the various forms of CHD results in unjustified referral of patients to cardiac surgery hospitals for complex invasive, costly and unsafe investigations (Gasilin V.S. et al., 1995).

From 15 to 30% of patients undergoing CAG have unchanged or only minimally changed coronary arteries (Poltavskaya M.G. et al., 1993; Maychuk E.Yu. et al., 1997). Given the overall prevalence of CHD, the number of patients with anginal symptoms and unchanged coronary arteries represents a substantial population.

Microvascular angina (or coronary syndrome X) was first described in the 1970s of the last century but still remains a subject of discussion among clinical researchers. The key point is the absence of atherosclerotic changes in the subepicardial coronary arteries in the presence of typical angina and ECG signs of myocardial ischaemia. Because of the severity of the symptoms and the chronic nature of the disease, patients undergo costly diagnostic work-up in clinics of various profiles and are treated, as a rule, for long periods and ineffectively, with the use of a large arsenal of drugs. The study of the pathogenetic mechanisms of coronary syndrome X (CSX) has been the subject of numerous investigations over recent decades (Chilian W.B., 1990; Maseri A. et al., 1991; Chauhan A., 1993; Lanza G.A., 1999; Bagger J.P., 2000). Some researchers associate the main cause of CSX with myocardial ischaemia (Bortone A.S. et al., 1989). Other authors consider impaired pain (nociceptive) sensitivity to be the primary cause of the disease (Shapiro L.M. et al., 1988; Fedele F., 1998).

It is known that one of the early and sensitive markers of myocardial ischaemia is regional wall motion abnormalities, which appear during stress before ECG ischaemic changes and precede the onset of anginal syndrome. The currently available literature data point to a high diagnostic value of stress echocardiography (stress-ECHO). Thus, E. Picano (2003) indicates a high sensitivity (78%) and specificity (86%) of stress-ECHO in the presence of coronary artery stenosis exceeding 70%. No significant decrease in sensitivity or specificity was found in different clinical groups. It has been shown that a negative result of stress echocardiography in most cases supports continued conservative treatment and the absence of need for invasive intervention, while a positive result supports myocardial revascularisation in 66% of cases. When choosing treatment strategy, stress-induced wall motion abnormalities can serve as evidence of haemodynamic significance of a coronary artery stenosis (or restenosis) in 50–70% of cases. At the same time, data have been reported on the high prognostic value of stress-ECHO in predicting adverse events in CHD patients. With a positive stress-ECHO result, the probability of adverse events increased fivefold, reaching 15% (D.V. Duplyakov et al., 2004).

However, until now the diagnostic capabilities of this method in CHD patients without lesions of the main coronary arteries have been little studied, and the available literature data are rather contradictory. Thus, N.N. Mikheev (2004) points to a high sensitivity of stress-ECHO in detecting myocardial ischaemia in coronary syndrome X. According to this study, the sensitivity of dipyridamole stress-ECHO at medium doses reached 97.6%, while that of transoesophageal atrial pacing stress-ECHO and of bicycle ergometry stress-ECHO was 76.7%. In contrast, foreign literature reports low sensitivity of stress-ECHO with respect to ischaemia developing in coronary syndrome X (E.G. Zouridakis, 2000).

Thus, defining the role of non-invasive diagnostic methods in the assessment of myocardial ischaemia and of the state of the coronary bed in syndrome X is a highly relevant problem of considerable practical importance. In this regard, the use of the capabilities of stress echocardiography in refining the diagnosis in patients with microvascular angina appears to be a promising and practically feasible approach.

Aim of the study

To investigate the clinical and instrumental criteria for the diagnosis of coronary heart disease in patients without haemodynamically significant stenosing lesions of the coronary bed.

Objectives of the study

1. To study the clinical and instrumental characteristics of patients without haemodynamically significant coronary artery stenoses on coronary angiography.

2. To assess the features of the angiographic picture in patients without haemodynamically significant coronary artery stenoses.

3. To study the features of the results of functional exercise ECG and ECHO tests in patients with coronary syndrome X.

4. To compare the results of stress echocardiography in patients with and without coronary syndrome X.

5. To determine the value of stress echocardiography in the diagnosis of coronary syndrome X.

Scientific novelty

Based on the analysis of the results of the clinical and instrumental examination of patients without haemodynamically significant coronary artery stenoses, heterogeneous groups of patients have been identified, including those with coronary syndrome X, as well as patients with specific features of the coronary bed structure and coronary artery spasm.

In patients without haemodynamically significant coronary artery stenoses, the frequency of detection of specific features of the coronary bed structure (hypoplasia, dilatation, myocardial bridges, and tortuosity of the coronary arteries) has been established.

In patients without haemodynamically significant coronary artery stenoses, specific features of coronary haemodynamics have been revealed, consisting in delayed passage of contrast medium through the coronary arteries.

The work demonstrates the significance of stress echocardiography in the diagnosis of coronary syndrome X. A relationship has been found between the results of stress echocardiography and the features of the coronary bed structure. It has been established that in patients with coronary syndrome X, in contrast to patients without this syndrome, discordance between stress echocardiography results by ECHO and ECG criteria is observed more frequently.

Practical significance

The work substantiates the feasibility of using stress echocardiography in cases with positive results of an exercise ECG test.

Taking into account the results obtained from the comprehensive instrumental examination, the criteria for referring patients to coronary angiography have been refined.

Main statements defended

1. Patients without haemodynamically significant coronary artery stenoses constitute a heterogeneous group, including patients with coronary syndrome X, as well as patients with specific features of the coronary bed structure and coronary artery spasm.

2. Stress echocardiography, as a supplement to the exercise ECG test, increases the diagnostic efficiency for coronary syndrome X.

3. The use of a comprehensive instrumental examination of patients with suspected coronary heart disease allows refinement of the criteria for their referral to coronary angiography.

The work was approved on 14 November 2008 at a joint meeting of the Department of Cardiology and General Therapy of the FSI "ESMC" of the Presidential Administration of the Russian Federation with the participation of physicians of the FSI "Central Clinical Hospital with Outpatient Clinic" of the Presidential Administration of the Russian Federation, and on 6 January 2009 at a joint meeting of the Departments of Internal Medicine I and Resuscitation, Internal Medicine II, Propaedeutics of Internal Medicine I and II, and Clinical Pharmacology of the Azerbaijan Medical University.

Publications

Three works have been published on the topic of the dissertation, two of which appear in central press.

Scope and structure of the work. The dissertation consists of an introduction, four chapters, conclusions, practical recommendations and a list of references. The text of the dissertation is set out on 116 pages and contains 18 figures and 14 tables. The bibliography includes 35 domestic and 147 foreign sources of information.