Evaluation of the Effectiveness of Pharmacological Treatment of Chronic Heart Failure in Patients with Ischemic Heart Disease

The dissertation is devoted to the evaluation of the effectiveness of pharmacological treatment of chronic heart failure (CHF) in patients with ischemic heart disease, with a cardiac surgery cohort included for comparative analysis. The work examines clinical, laboratory and instrumental criteria used to assess CHF severity in the decompensation phase and after stabilization, as well as in the early and late postoperative periods in cardiac surgery patients. Particular attention is given to the brain natriuretic peptide (BNP) system as a biomarker of CHF severity and of postoperative complications, and to a comparative evaluation of patients' quality of life under therapeutic and surgical treatment regimens.

Relevance of the study.

Every year, new and new cases of chronic heart failure (CHF) are diagnosed worldwide. According to the World Health Organization (WHO), CHF is the most frequent cause of hospitalization in elderly people. Direct and indirect costs of heart failure (HF) worldwide are estimated at billions of dollars. WHO experts consider CHF an "epidemic of the 21st century." According to their conclusions, a worsening of the situation and an increase in the scale of the problem are expected in the future, since with an increase in average life expectancy the number of people suffering from CHF will also grow. Five-year survival after diagnosis is 50%, and ten-year survival is less than 25% [The Task Force of the Working Group on Heart Failure of the European Society of Cardiology. The treatment of heart failure, 1997]. According to epidemiological studies of the past 5 years conducted in our country under the auspices of VNOK and OSSN, in 2002 in the Russian Federation there were 8.1 million people with clear signs of CHF, of whom 3.4 million had terminal, FC III — IV disease [Ageev F.T. et al., 2004; Russian National Recommendations of VNOK and OSSN on the Diagnostics and Treatment of CHF, 2007].

One-year mortality of patients with clinically evident HF reaches 26–29%, meaning that between 880 and 986 thousand patients with HF die each year in the Russian Federation [Belenkov Yu.N., Oganov R.G., 2007]. In 2003, decompensation of CHF was the cause of hospitalizations in hospitals with cardiology departments in almost every second patient (49%), and CHF appeared in the diagnosis of 92% of patients hospitalized in such hospitals. In 4/5 of all HF patients in Russia, the disease is associated with arterial hypertension, and in 2/3 of patients with IHD. Until recently, the treatment of ischemic CHF and ischemic cardiomyopathy was the prerogative of cardiologist-therapists [Belenkov Yu.N., Mareev V.Yu., Ageev F.T., 2006]. However, over the past 8–10 years, in connection with the rapid progress of high technologies, surgical methods of treatment have been increasingly used in the management of ischemic CHF [Joyce D., et al., 2003; Baker D.W., et al., 1994; Yusuf S., Zucker D., 1994; Tsuyuki R.T., et al., 2006; Hirashiki A., et al., 2006]. First of all, it is necessary to single out as the most popular intervention the operation of direct myocardial revascularization, various modifications of cardiomyoplasty, partial ventriculotomy, the application of a restrictive elastic mesh, and finally heart transplantation [Belenkov Yu.N., 2002; Shumakov V.I., 1995.]. Methods of cardiac resynchronization therapy and implantation of mechanical circulatory support devices, called left ventricular "bypass," are becoming increasingly widespread [Bokeriya L.A., 2000; Bristow M., et al., 2004; Cleland J., et al., 2005]. The proportion of IHD patients with very low EF (<30%), ischemic cardiomyopathy and CHF FC III — IV is steadily growing [Mareev V.Yu., 2006]. For example, in 2000 at the P.A. Kupriyanov Clinic of Cardiovascular Surgery there were 9 such patients out of 116 coronary bypass operations, amounting to 8%, and by December 2005 there were 37 patients out of 254 bypass operations (i.e., 14.5%). How should the effectiveness of the performed operation be evaluated in this category of patients, and according to which criteria? For the cardiologist it is the most pressing question [Belenkov Yu.N., 1996]. Uniform recommendations and approaches have not yet been developed. If for patients with angina the criterion of effectiveness of surgical intervention is the increase in physical activity in the absence of angina syndrome, then with respect to HF regression such conclusions are invalid. The presence of dyspnea, atelectasis, moist rales in the lungs, fluid in the pleural cavity, and features of postoperative hemodynamics in the form of tachycardia and hypervolemia often mask the main symptoms of HF and greatly complicate assessment of its severity. According to L. Goldman et al., agreement between two independent experts on the functional class of CHF was noted in 55% of cases, and when compared with VEM data only in 50%. According to the Heart Failure Department of the A.L. Myasnikov Institute of Cardiology [Gerasimova V.V., 1991], the opinions of three independent experts in the assessment of the condition of 1034 patients with CHF coincided only in 63.4% of cases. What then can be said about assessment of the condition of one and the same patient by different specialists, a cardiologist and a cardiac surgeon [Mareev V.Yu., 2004]. That is why there are such contradictory evaluations of the effectiveness of surgical treatment of CHF on the part of the operating surgeons and the cardiologists who subsequently observe the patients [Packer M., 1993].

The unresolved problem of reliable and highly sensitive evaluation of the effectiveness of surgical treatment of CHF in the early and late postoperative periods determined the goal of our study. Aim of the study: on the basis of a comparative analysis of clinical, laboratory and instrumental methods of examination, to evaluate the effectiveness of pharmacological and surgical treatment of patients with chronic heart failure. Research objectives:

1. To establish the most significant clinical, echocardiographic and biochemical indicators for diagnosing the severity of CHF in patients in the decompensation and compensation phases.

2. To determine the most informative criteria for diagnosing the severity of CHF in patients undergoing cardiac surgery under conditions of cardiopulmonary bypass and on the beating heart in the early and late postoperative periods.

3. To carry out a comparative evaluation of the effectiveness of therapeutic and surgical methods of CHF treatment from the standpoint of assessing patients' quality of life.

4. To investigate the brain natriuretic peptide system in cardiac surgery patients and the influence of various intraoperative factors on it.

5. To study the prognostic role of the brain natriuretic peptide level in cardiac surgery patients.

Statements submitted for defense:

1. Brain natriuretic peptide is a more sensitive criterion than echocardiographic indicators reflecting changes in the severity of heart failure; it significantly correlates with the cardiac index and pulmonary artery wedge pressure measured directly. The absence of rapid dynamics of brain natriuretic peptide against the background of intensive therapy is a poor prognostic factor.

2. An increase in the plasma concentration of brain natriuretic peptide is observed in all patients after myocardial revascularization, both with and without the use of cardiopulmonary bypass. In the early postoperative period, the level of brain natriuretic peptide cannot serve as a criterion for evaluating the success of surgical treatment of chronic heart failure.

3. The quality of life of patients with severe heart failure whose treatment is supplemented by myocardial revascularization is higher than that of patients receiving only conservative therapy.

4. There is a strong direct correlation between the preoperative level of brain natriuretic peptide and the frequency of occurrence of low cardiac output syndrome and rhythm disturbances (atrial fibrillation–flutter) in the early postoperative period, which makes it possible to predict and timely prevent the development of dangerous postoperative complications.

Scientific novelty of the study:

The scientific novelty of the work is determined by the presentation of new facts concerning the diagnostic significance of the main hemodynamic and biochemical parameters in determining the severity of CHF. On the basis of correlation analysis of the results of comprehensive clinical and instrumental examination of patients with chronic heart failure, the most sensitive and specific diagnostic criteria have been identified, allowing high-reliability assessment of the effectiveness of one or another type of treatment.

The prognostic role of brain natriuretic peptide in the early and late postoperative periods, as well as the influence of various intraoperative factors on it, has been investigated; predictors of complicated course of the postoperative period in cardiac surgery patients have been determined.

A comparative evaluation of the effectiveness of therapeutic and surgical methods of CHF treatment has been carried out from the standpoint of assessing patients' quality of life.

Practical significance:

A set of the most reliable and informative criteria for diagnosing the severity of CHF in patients receiving conservative and cardiac surgical treatment has been defined, combining the accessibility of the methods for the practicing physician, safety for the patient and economic efficiency for the health care system. The combination of ultrasound and biochemical indicators in comprehensive non-invasive examination of patients makes it possible to assess with high sensitivity the effectiveness of the therapy being conducted or the cardiac surgery performed.

The data presented in the work on the prognostic significance of BNP will allow cardiac surgeons to carry out risk stratification of patients planned for surgical treatment of CHF.

Implementation of research results:

The results of the study are used in the scientific and clinical-diagnostic work of the Department and Clinic of Faculty Therapy, the 1st Department of Surgery for Advanced Training of Physicians, the Department of Naval Hospital Therapy of the Military Medical Academy, the cardiology departments of the 442nd Military Clinical Hospital of the Ministry of Defense of the Russian Federation, in lecture courses on clinical pharmacology for the 6th year of the II and IV faculties of physician training and for clinical residents of 2–3 years of study, in cardiology training cycles of the VI faculty.

Approbation and publication of research materials:

The results of the research were reported and discussed at the IV, V, VI All-Russian Conference of the Society of Heart Failure Specialists (2003–2005), the 1st All-Russian Congress of the Society of Heart Failure Specialists, the I and II Congress on Heart Failure (Moscow, 2007–2008), the Jubilee Conference dedicated to the 170th anniversary of the Department of Faculty Therapy of the Military Medical Academy (Saint Petersburg, 2006). Eleven publications have been published on the topic of the study. Volume and structure of the work.

The dissertation is presented on 139 pages of typewritten text and consists of an introduction, 5 chapters, a conclusion, findings, practical recommendations, appendices and a bibliography comprising 199 sources, including 41 domestic and 158 foreign ones. The text is illustrated with 21 tables, 7 figures and graphs.