Clinical Significance of Functional Mitral Regurgitation and Disorders of Transmitral Blood Flow in Patients with Complicated Forms of Coronary Heart Disease

The dissertation is devoted to the study of functional mitral regurgitation (FMR) and disorders of transmitral blood flow in patients with complicated forms of coronary heart disease, including acute myocardial infarction and bradyarrhythmias in elderly and senile patients. The work combines clinical examination with the use of quantitative Doppler echocardiographic methods (PISA and Q-DE) to assess regurgitation and diastolic function. It investigates the influence of different modes of temporary cardiac electrical stimulation, as well as pharmacotherapy with ACE inhibitors (captopril) and angiotensin II receptor antagonists (valsartan), on hemodynamics and clinical outcomes.

Coronary heart disease (CHD) is the principal problem in clinical internal medicine and is characterized in WHO materials as the epidemic of the twentieth century. This is justified by the growing incidence of CHD among people of different age groups, the high percentage of disability, and the fact that it remains one of the leading causes of mortality. Death occurs as a result of progressive heart failure (HF) or suddenly, presumably due to ventricular tachyarrhythmias, bradyarrhythmias, and AV block. The loss of part of the functioning myocardium as a result of infarction, repeated ischemic episodes, and chronic pressure or volume overload of the heart is accompanied by a complex of structural changes involving both damaged and undamaged regions of the myocardium. These changes in the structure and geometry of the cardiac chambers, termed "cardiac remodeling," often precede the clinical manifestation of HF, may independently aggravate systolic and diastolic ventricular dysfunction, and adversely affect the quality of life and prognosis of patients.

Initial attempts at pharmacological influence on peri-infarction zones in order to prevent left ventricular (LV) myocardial remodeling, and subsequent attempts using modern pharmacological and other interventions, proved insufficiently effective but yielded a large body of clinically useful information for understanding the processes of LV myocardial remodeling in patients with myocardial infarction (MI). The problem of survival, quality of life, and restoration of working capacity in patients who have suffered acute myocardial infarction (AMI) is largely determined by treatment strategy. By the end of the first year, despite the use of modern treatment methods, about 25% of patients who have suffered Q-wave myocardial infarction die.

In recent years, it has been established that some patients with AMI develop functional mitral regurgitation (FMR), which is of no small importance in the development and progression of heart failure (HF). However, its role in the process of LV myocardial remodeling has not been fully clarified. Investigation of the features of FMR in patients with AMI will broaden our fundamental knowledge in the field of LV remodeling and clarify the sequence of events occurring in the heart of patients with large-focal or transmural AMI and FMR.

According to the World Health Organization, the increase in the number of elderly and senile persons is a characteristic demographic phenomenon of our era [Kitzman D.W., 2001]. With increasing age, progression of sclerodegenerative processes in the myocardium affecting the cardiac conduction system leads to an increased frequency of bradyarrhythmias [Melent'yev A.S., 1995; D'Este D., 2001]. Disturbance of the spectrum and parameters of diastolic transmitral blood flow (DTMBF) in patients with CHD and bradyarrhythmias leads to the development of diastolic and subsequently systolic HF. Investigation of transmitral flow disorders and their role in the pathogenesis of HF in patients with CHD will make it possible to determine the place of pharmacological and non-pharmacological interventions aimed at normalizing transmitral blood flow. In recent years, studies have been conducted on the comparative evaluation of the efficacy of ACE inhibitors and angiotensin II receptor antagonists in the acute period of MI. The results of these studies are contradictory: the advantage of angiotensin II receptor antagonists in some studies and the absence of differences between them in others. The definitive answer to this question will be obtained when several large studies devoted to this problem are completed. At present, it is generally accepted that the use of angiotensin II receptor antagonists in patients with MI is advisable when there is intolerance to ACE inhibitors.

Relevance of the study

The problem of survival, quality of life, and restoration of working capacity in patients who have suffered AMI is largely determined not only by the extent of myocardial damage but also by the developing complications of the disease and treatment strategy. A number of recent works have shown [Enriquez-Sarano M., et al., 2000; Enriquez-Sarano M., et al., 2001] that 40% of patients with transmural or large-focal MI develop FMR, and mortality in this group reaches 36% of patients. Five-year survival of MI patients with severe FMR does not exceed 40% compared with 72% of patients without FMR.

Functional mitral regurgitation develops in myocardial infarction as a result of local or generalized LV dysfunction in patients with normal leaflets and chordae. An important role in the development of FMR is played by the change in LV shape from ellipsoidal to spherical, leading to displacement of the papillary muscles [Kono T., et al., 1992], restriction of mitral valve mobility, and impaired leaflet coaptation [Faggiano P., et al., 2000]. Dilatation of the mitral annulus and certain other factors influence the appearance and development of FMR. The development of optimal clinical methods for the early diagnosis of FMR and the assessment of its influence on diastolic transmitral blood flow (DTMBF) is a promising line of research on this relevant cardiological problem.

Investigation of DTMBF disorders and their role in the pathogenesis of HF in patients with complicated forms of CHD (FMR, bradyarrhythmias) will make it possible to determine the place of pharmacological and non-pharmacological (invasive) interventions aimed at normalizing transmitral blood flow. This will make it possible to slow the progression of HF and improve the prognosis of this group of patients. Investigation of this relevant problem will serve as a stimulus for further in-depth studies in this scientific area of cardiology.

Aim of the study

To develop diagnostic approaches and methods for the correction of functional mitral regurgitation and disorders of diastolic transmitral blood flow in patients with complicated forms of CHD.

Objectives of the study

1. To study the main quantitative indicators of the regurgitant blood flow: regurgitant orifice area, regurgitant volume, and regurgitant fraction using quantitative Doppler echocardiography methods (PISA and Q-DE methods) in patients with AMI and FMR.

2. To compare the results of determining the quantitative indicators of FMR calculated by the color Doppler mapping of the proximal isovelocity regurgitant flow (PISA method) with the results of quantitative Doppler echocardiography (Q-DE method) in patients with AMI.

3. To determine the clinical significance of the main quantitative indicators of FMR in patients with AMI that are the most significant (informative) for assessing the severity of mitral regurgitation.

4. To develop a classification of FMR severity in patients with AMI, based on the value of the regurgitant fraction calculated from Doppler echocardiography data (PISA and Q-DE methods).

5. To study the influence of mitral regurgitation on DTMBF in patients with AMI complicated by FMR.

6. To analyze the efficacy and safety of captopril and valsartan in patients with AMI and FMR.

7. To investigate age-related features of disorders of diastolic transmitral blood flow and of diastolic and systolic LV functions in elderly and senile patients with CHD and bradyarrhythmias and to evaluate the clinical and hemodynamic effect of different methods of cardiac pacing.

8. To evaluate the clinical and hemodynamic efficacy of captopril in elderly patients with CHD and bradyarrhythmias during temporary cardiac electrical stimulation (ES).

Scientific novelty of the study

The quantitative indicators of FMR in patients with AMI have been studied and their influence on clinical and hemodynamic parameters and on LV remodeling processes in the acute period of the disease has been evaluated.

The fundamental possibility of, and methodological development for, the combined use of quantitative Doppler echocardiography with color mapping of the proximal isovelocity regurgitant flow region has been demonstrated in order to improve the accuracy of assessment of the regurgitant flow and the severity of mitral regurgitation in patients with AMI.

A classification of the severity of mitral regurgitation in patients with AMI and FMR has been developed on the basis of the regurgitant fraction value, allowing the severity of regurgitation to be objectified and the prognosis and treatment strategy of AMI patients complicated by FMR to be determined. The clinical and hemodynamic efficacy and safety of ACE inhibitors and angiotensin II receptor antagonists in AMI patients complicated by FMR have been evaluated.

Age-related features of changes in DTMBF and LV systolic function in CHD patients with bradyarrhythmias and their role in the development of HF have been studied. The influence of different modes of temporary cardiac pacing on DTMBF and LV systolic function in elderly and senile CHD patients with bradyarrhythmias has been evaluated.

The possibility of non-pharmacological correction of hemodynamic disorders in elderly and senile CHD patients by means of dual-chamber pacing has been demonstrated, with evaluation of the influence of different AV intervals on transmitral blood flow and LV contractility.

The hemodynamic efficacy of the ACE inhibitor captopril in elderly and senile CHD patients with an artificial pacemaker has been evaluated in relation to the method of cardiac electrical stimulation and the indicators of diastolic transmitral blood flow.

Practical significance

The conducted studies have made it possible to form a more accurate idea of the interrelation between FMR, transmitral blood flows, LV systolic and diastolic functions, and the state of hemodynamics in patients with different forms of CHD.

For an objective assessment of the severity of the patient's condition and disease prognosis in AMI patients with FMR, quantitative indicators of regurgitation must be determined: the regurgitant fraction, the regurgitant orifice area, and the regurgitant volume.

For a more accurate determination of FMR indicators in AMI patients, the combined use of two quantitative Doppler echocardiography methods (Q-DE and PISA) is necessary. The results of measurement of the regurgitant fraction, objectively characterizing the severity of FMR in AMI patients, should be reflected in the diagnosis, which is important for assessing the patient's condition and choosing treatment methods. To reduce mitral regurgitation in the acute period of myocardial infarction complicated by FMR, the use of angiotensin II receptor antagonists (valsartan) is useful and safe.

In view of the rapid development of HF in elderly and senile CHD patients with bradyarrhythmias against the background of age-related structural and functional changes in the cardiovascular system, immediate use of cardiac pacing is necessary.

It has been demonstrated that in elderly and senile patients, when choosing the optimal type and mode of temporary cardiac pacing, it is necessary to take into account the influence of the artificial pacemaker on LV diastolic filling, which is of essential importance for the hemodynamic function of the heart in patients over 60 years of age. The AV interval in elderly and senile patients with dual-chamber pacing should not exceed 150 ms.

Forms of implementation and publications

The results of the study are successfully used in the work of the cardiac resuscitation unit with the department of emergency cardiology of City Clinical Hospital No. 7 and in the teaching and research process of the Department of Hospital Therapy No. 2 of I.M. Sechenov Moscow Medical Academy.

Based on the materials of the dissertation, the following works have been published:

1. Influence of temporary sequential atrioventricular cardiac pacing on hemodynamics // Kardiologiya. — 1984. — Vol. 24. — No. 6. — P. 49–51. (co-authors: Kapralova T.A., Gilyarovsky A.K.).

2. Temporary cardiac pacing in paroxysmal arrhythmias in patients with coronary heart disease // Kardiologiya. — 1986. — Vol. 26. — No. 4. — P. 42–44. (co-authors: Gilyarovsky A.K., Simonov V.I.).

3. Complications of temporary transvenous cardiac pacing // Kardiologiya. — 1987. — Vol. 27. — No. 5. — P. 94–95. (co-authors: Gilyarovsky V.K., Simonov V.I.).

4. Features of hemodynamics during dual-chamber cardiac pacing // Kardiologiya. — 1987. — Vol. 27. — No. 9. — P. 72–77. (co-authors: Drogaytsev A.D., Gruzdev A.K., Gilyarovsky A.K.).

5. Electrophysiological localization of blocks in patients with atrioventricular conduction disturbance // Kardiologiya. — 1987. — Vol. 27. — No. 7. — P. 105–108. (co-authors: Gilyarovsky A.K., Simonov V.I.).

6. Aortocoronary bypass grafting in the early period after the onset of myocardial infarction // Kardiologiya. — 1989. — Vol. 29. — No. 6. — P. 9–15. (co-authors: Solov'yov G.M., Mikheev A.A., Petrovsky P.F.).

7. Electrical destruction of the atrioventricular junction in a patient with post-infarction ventricular tachycardia // Kardiologiya. — 1991. — Vol. 31. — No. 3. — P. 71–72. (co-authors: Gilyarovsky A.K., Cherkasova N.A., Simonov V.I.).

8. Diastolic function of the left ventricle in patients with coronary heart disease // Kardiologiya. — 1993. — No. 5. — P. 12–15. (co-authors: Pavlova I.F., Simonov V.I., Batishchev A.A.).

9. Damage to the cardiac conduction system in patients with neural amyotrophy of Charcot-Marie // Kardiologiya. — 1994. — Vol. 34. — No. 7. — P. 93–94. (co-authors: Simonov V.I., Cherkasova N.A., Golshmid M.V.).

10. Doppler echocardiographic study of left ventricular diastolic function in patients with coronary heart disease during temporary single- and dual-chamber cardiac pacing // Kardiologiya. — 1995. — Vol. 35. — No. 6. — P. 43–45. (co-authors: Pavlova I.F., Simonov V.I., Cherkasova N.A.).

11. Certain features of intracardiac hemodynamics in patients with bradyarrhythmias during VVI, DVI, AAI cardiac pacing and their clinical significance // Kardiologiya. — 1999. — No. 2. — P. 56–59. (co-authors: Petrovskaya N.V., Golshmid M.V., Simonov V.I.).

12. Echocardiographic quantitative assessment of functional mitral regurgitation in patients with acute myocardial infarction // Ekhografiya. — 2003. — Vol. 4. — No. 3. — P. 273–280. (co-authors: Komarova I.S., Mikhailov A.A.).

13. Assessment of quantitative indicators of mitral regurgitation in patients with myocardial infarction // Current Issues of Clinical Medicine. / Edited by Karaulov A.V. — Moscow. — Regional Association of the Russian Academy of Natural Sciences. — 2002. — Vol. 2. — P. 31–32. (co-authors: Komarova I.S., Lazutin V.K., Cherkasova N.A.).

14. Mitral regurgitation in patients with myocardial infarction // Ultrasound and Functional Diagnostics. — 2004. — No. 1. — P. 75–80. (co-authors: Komarova I.S., Mikhailov A.A.).

15. Functional mitral regurgitation in patients with myocardial infarction // Russian National Congress of Cardiologists. From Preventive Check-ups to High Technologies. — Moscow. — 2006. — P. 143. (co-authors: Komarova I.S., Shik M.V.).

16. Transvenous electrical destruction of the AV junction in elderly patients // Clinical Gerontology. — 1995. — No. 2. — P. 8–10. (co-authors: Cherkasova N.A., Simonov V.I., Gilyarovsky A.K.).

17. Changes in left ventricular diastolic function in patients with different types of cardiac pacing during captopril treatment // Collection of Research and Practical Papers of the Research and Practical Conference of the Polyclinic of the Russian Ministry of Foreign Affairs / Ministry of Foreign Affairs of the Russian Federation. Administrative Department. — Moscow. — 1999. — P. 29–30. (co-authors: Golshmid M.V., Simonov V.I., Lazutin V.K.).

18. Age-related features of central and intracardiac hemodynamics in patients with bradyarrhythmias over 60 years of age // Current Issues of Clinical Medicine. / Edited by Karaulov A.V. — Moscow. — Regional Association of the Russian Academy of Natural Sciences. — 2002. — Vol. 2. — P. 24–25. (co-authors: Petrovskaya N.V., Golshmid M.V., Simonov V.I.).

19. Hemodynamic efficacy of captopril in the treatment of heart failure in elderly and senile patients with an artificial pacemaker // Current Issues of Clinical Medicine. / Edited by Karaulov A.V. — Moscow. — Regional Association of the Russian Academy of Natural Sciences. — 2002. — Vol. 2. — P. 33–34. (co-authors: Petrovskaya N.V., Golshmid M.V., Simonov V.I.).

Propositions submitted for defense

1. Functional mitral regurgitation is one of the severe complications of AMI, contributing to dilatation of the cardiac chambers, development of HF, and worsening of the prognosis.

2. Determination of the quantitative indicators of FMR makes it possible to objectify the severity of mitral regurgitation and the treatment strategy in patients with AMI.

3. To improve the accuracy and quality of FMR measurements, two diagnostic methods must be used: color Doppler mapping of the proximal isovelocity surface area (PISA method) and quantitative Doppler echocardiography (Q-DE method).

4. The main indicators determining the severity of FMR are the regurgitant fraction, the regurgitant orifice area, and the regurgitant volume.

5. Disturbance of transmitral blood flow caused by AV dissociation worsens diastolic filling and systolic function of the LV, which disturbs intracardiac hemodynamics and accelerates the development of HF in CHD patients with bradyarrhythmias.

6. Restoration of the normal sequence of cardiac chamber contraction and optimization of the AV interval during dual-chamber electrical stimulation prevents the development of the pacemaker syndrome and improves hemodynamic indicators in CHD patients with bradyarrhythmias.

7. The use of angiotensin II receptor antagonists (valsartan) in AMI patients with FMR reduces the indicators of regurgitation and the HF class. Captopril in elderly and senile CHD patients with an artificial pacemaker improves the clinical condition of patients and LV systolic and diastolic function.

Approval of the dissertation and implementation of the research results

The dissertation was approved at the joint conference of the Department of Hospital Therapy No. 2 of the Faculty of Medicine of I.M. Sechenov Moscow Medical Academy and the staff of City Clinical Hospital No. 7, Moscow. The research results and the principal methods are used in the work of the cardiac resuscitation unit and the department of emergency cardiology of City Clinical Hospital No. 7, and in the teaching and research process of the Department of Hospital Therapy No. 2 of I.M. Sechenov Moscow Medical Academy.

Structure and volume of the work

The dissertation is presented on 268 pages of typewritten text, includes 37 tables, is illustrated with 89 figures, and consists of an introduction, seven chapters, a conclusion, findings, and practical recommendations. The bibliography includes 72 works by domestic and 215 by foreign authors.