Cardiac Pacing in the Correction of Chronic Heart Failure: Clinical and Instrumental Evaluation of Efficacy, Quality of Life, Stratification of Complications and Outcomes Based on a 5-Year Prospective [Study]

The dissertation is devoted to studying the possibilities of permanent cardiac pacing in the correction of chronic heart failure (CHF). Based on a five-year retrospective analysis, the effectiveness of different pacing modes (single-chamber VVI and dual-chamber DDD) is evaluated, along with a method of individual parameter selection using stress echocardiography. The work separately considers the influence of intraventricular electromechanical asynchrony on the course of CHF and a comparative analysis of drug treatment and cardiac resynchronization therapy (CRT) using biventricular pacing. The study covers the clinical and instrumental assessment of disease dynamics, quality of life, frequency of complications, hospitalizations, and survival of patients with implanted pacemakers.

GENERAL CHARACTERIZATION OF THE WORK

Relevance of the topic

Decompensation of chronic heart failure (CHF), despite certain advances in drug treatment, is one of the most common causes of hospitalization in persons aged 65 and over, ranking third worldwide among causes of hospitalization. [Gottdiener J.S. et al., 2000; McMurray J., Stewart S., 2000; Baydina O.I., 2002]. In the population over 45 years of age, the number of CHF cases doubles every 10 years [Mareev V.Yu., 2007].

Progression of CHF is accompanied by a significant deterioration in patients' quality of life and is one of the main causes of death in the population. This applies primarily to cases with high grades of functional class (FC) according to NYHA and to the development of resistance to drug therapy. In 2002, the Russian Federation had 8.1 million persons with documented signs of CHF, of whom 3.4 million had FC III–IV of the disease. In Russia, between 880 and 986 thousand patients die from CHF annually [Danielyan M.O. 2001; Olbinskaya L.I., Sizova Zh.M., 2001; McCullough P.A. et al., 2002; Ansari M., Massie B., 2003; Levy D. et al., 2004].

Myocardial dysfunction with its structural remodelling is a key link in the development and progression of heart failure [Braunwald E., 1997; Sidorenko B.A., Preobrazhensky D.V., 2004]. Identification of myocardial dysfunction is a mandatory condition for the diagnosis of CHF [Mareev V.Yu., Belenkov Yu.N. 2002; Boytsov S.A. 2005; Mareev V.Yu. 2007]. A promising method for studying cardiac muscle function is echocardiography with Doppler imaging, including tissue Doppler imaging of the myocardium [Pavlyukova E.N. et al., 2003; Alekhin M.N., 2005]. However, the possibilities of using tissue Doppler imaging in CHF patients have been insufficiently studied, and the available research findings are contradictory.

In Russia, CHF is associated with arterial hypertension (AH) in 4/5 of cases and with coronary heart disease (CHD) in 2/5 of cases [Ageev F.T., Danielyan M.O. 2004]. A decrease in coronary blood flow is accompanied by changes in metabolism and reduced myocardial perfusion, and consequently by the development of hibernating myocardium, which leads to the progression of systolic and diastolic myocardial dysfunction [Shumakov V.I. et al., 2003; Shlyakhto E.V. et al., 2005; Schulz R., Heusch G., 2000; Saidova M.A., 2005].

In most cases, the course of CHF is accompanied by the development of rhythm and conduction disorders. The occurrence of arrhythmias markedly aggravates the disease and promotes rapid progression of CHF [Shlyakhto E.V., Novikova I.V. 2001]. The frequency of arrhythmias in patients with CHD is extremely high. Thus, supraventricular extrasystole occurs in 40–50% of cases, ventricular extrasystole in 80–90% of cases, and intraventricular conduction disorders are detected in 80% of cases. Supraventricular and ventricular extrasystole, atrial fibrillation, and sustained and non-sustained ventricular tachyarrhythmias can complicate the course of CHF. In severe CHF, sudden death may also occur against a background of bradyarrhythmias [Schaurte P., Scherlag B. et al. 1998; Eckardt L., Haverkamp W., et al., 2000]. Therefore, one of the directions in the treatment of CHF is the management of rhythm and conduction disorders.

Therapy for CHF using a combination of ACE inhibitors and beta-blockers, as well as other medications, has its limits of effectiveness and at a certain stage becomes ineffective. [Feldman A., 2001; Grassi G., et al., 2004].

In this regard, in recent decades great hopes in correcting disorders associated with CHF have been placed on the use of permanent cardiac pacing, both with the traditional single-chamber or dual-chamber pacing and with the modern method — cardiac resynchronization therapy (CRT) by means of biventricular pacing.

The main efforts in the treatment of CHF should be directed at restoring the ability of the heart to fill with blood during diastole and to contract during systole, as close as possible to the working mode of a healthy myocardium [Novikov V.I., Samoilovich T.M., 2001; Obrezan A.G., Vologdina I.V., 2002]. The use of cardiac pacing methods makes it possible not only to restore rhythm and conduction disorders but also to improve systolic and diastolic myocardial function.

The implantation of a pacemaker does not halt the progression of CHD, but the clinical picture of CHD in these patients changes. [Kolletis T., Kremastinos D. et al., 1995; Barold S., Stroobandt R., 2004]. The use of electrocardiographic techniques to detect the progression of coronary insufficiency in patients with ventricular pacing provides extremely little information. Therefore, methods that allow visualization of the myocardium, in particular echocardiography and its modification, stress echocardiography, are of particular importance in this category of patients.

Until now, in most cases, standard averaged values of pacing parameters are used when selecting pacing parameters. The use of cardiac pacing in patients with chronic heart failure, especially in cases caused by CHD, requires an individual approach to the selection of pacing parameters [Rybkina T.V., 1996; Yuzvinkevich S.A., 1998; Barold S., 2004; Iskenderov B.G. 2005]. Studies devoted to this issue are few, and there are no long-term observations of hemodynamic parameters, quality of life, and survival with different methods of selecting parameters and pacing modes.

In recent years, close attention has been paid to disorders of coordinated work of individual myocardial regions, united under the term intraventricular asynchrony [Martsinkevich G.I., Sokolov A.A., 2005]. Many patients with CHF have asynchronous electrical activation of the ventricles. The main marker of electrical asynchrony is a QRS width > 120 ms. According to the data of V.S. Nikiforov (2006), the deterioration of systolic and diastolic function, as well as the progression of CHF, is accompanied by an increase in intraventricular asynchrony. The identification of this category of patients as a separate group is of practical importance, since the presence of intraventricular asynchrony leads to a significant increase in the probability of sudden cardiac death and a shortening of the lifespan. Drug therapy proves to be of little effectiveness both in restoring synchrony and in preventing the progression of CHF.

Relatively recently, a modern electrophysiological method — cardiac resynchronization therapy — has appeared in the arsenal of heart failure treatment. With the help of biventricular pacing, the electrical activity of the right and left ventricles is synchronized, which leads to improved cardiac contractility [Khirmanov V.N. et al., 2001; Abraham W., 2003; Kuznetsov V.A. et al., 2005]. However, there are data on the low effectiveness of CRT in 30% of persons with signs of electrical asynchrony [Reuter S. et al., 2002; Kass D., 2003]. Therefore, an extremely important task is the identification of additional markers of intraventricular asynchrony, on the basis of which an optimal approach to the use of cardiac resynchronization therapy could be developed. In addition, there is a need to select biventricular pacing parameters during the follow-up of these patients [Lane R.E. et al., 2004].

The aim of the work is to study the possibilities of cardiac pacing in correcting myocardial dysfunction in CHF using different pacing modes and methods of selecting pacing parameters through a five-year retrospective analysis of treatment effectiveness, quality of life, complications, and outcomes of the disease.

Research objectives:

1. To evaluate the effect of single-chamber VVI and dual-chamber DDD cardiac pacing on disease dynamics in CHF patients with established indications for pacemaker implantation.

2. To compare the effect of single-chamber and dual-chamber cardiac pacing on the course of CHF depending on the method of selecting pacing parameters — the empirical method of selection and the selection of pacing parameters using stress echocardiography with a sequential increase in the pacing rate of the implanted pacemaker.

3. To study changes in the clinical picture of CHD in patients with an implanted pacemaker under different pacing modes and different methods of selecting pacing parameters.

4. To study the effect of intraventricular asynchrony on the course of chronic heart failure.

5. To determine the effectiveness of correcting intraventricular asynchrony using drug treatment and cardiac resynchronization therapy with biventricular pacing, assessing disease dynamics, quality of life, and survival in patients with CHF.

6. To determine additional criteria for selecting CHF patients for cardiac resynchronization therapy, as well as parameters and methods for selecting the biventricular pacing mode.

Scientific novelty

1. It has been proved that the implantation of a single-chamber pacemaker (PM) is accompanied by marked progression of CHF. After one year, the severity indicators of CHF are significantly worse than the baseline values. The effectiveness of drug therapy is significantly higher than that of this pacing mode.

2. For the first time in CHF patients with established indications for PM implantation, a five-year analysis of disease dynamics has been performed depending on the pacing mode and the method of selecting pacing parameters. It has been established that the use of stress echocardiography with reprogramming of the implanted PM rate as a method of individual selection of pacing parameters makes it possible to significantly improve the course of CHF and quality of life parameters, which is accompanied by reduced mortality from cardiovascular causes and improved survival, regardless of the pacing mode. Medical care seeking, frequency of hospitalizations, and the need for PM reprogramming are also reduced.

3. For the first time in patients with PM syndrome, a study has been conducted to detect the progression of coronary insufficiency using stress echocardiography. It has been revealed that PM syndrome masks the progression of coronary insufficiency. An analysis has been performed of the frequency of ultrasound ischemic markers depending on the severity of PM syndrome. It has been established that ultrasound markers of ischemia were recorded significantly more often in patients with a moderate severity of PM syndrome.

4. It has been revealed that the implantation of a pacemaker in patients with CHD leads to a change in the character of the pain syndrome. The use of stress echocardiography by reprogramming the pacing rate of the PM makes it possible to detect the progression of coronary insufficiency and to select adequate anti-ischemic therapy, which leads to a reduction in death from myocardial infarction.

5. The effect of intraventricular asynchrony on CHF dynamics, quality of life, and survival over 3 years of follow-up has been studied. It has been proved that in patients with electrical asynchrony, markers of electromechanical asynchrony such as intraventricular and interventricular asynchrony are detected significantly more frequently. It has been shown that the presence of intraventricular asynchrony in general, and electrical asynchrony in particular, leads to the progression of CHF, deterioration of quality of life, and reduced survival. It has been proved that electromechanical asynchrony reduces survival among CHF patients to a greater extent than electrical asynchrony. An algorithm for detecting asynchrony in CHF patients has been proposed for the first time.

6. An analysis of the effect of drug treatment and cardiac resynchronization therapy (CRT) using biventricular pacing on intraventricular asynchrony in CHF patients has been performed. It has been proved that the use of CRT significantly improves and/or restores intraventricular synchrony, which is accompanied by a long-term (within 3 years) positive dynamics of CHF, improved quality of life parameters, reduced frequency of hospitalizations, and improved survival.

7. It has been revealed that the effectiveness of CRT is related to a greater extent to the restoration of electromechanical synchrony parameters than to electrical synchrony alone. It has been established that, for the selection of patients for CRT, it is necessary to examine not only the QRS width as a marker of electrical asynchrony but also such parameters as the mechanical interventricular delay and the intraventricular asynchrony index (according to echocardiography using pulsed-wave Doppler and tissue Doppler imaging). The possibility of echocardiographic techniques using pulsed-wave Doppler and tissue Doppler myocardial imaging in selecting atrioventricular and interventricular delay parameters in patients with CRT using a biventricular pacemaker has been demonstrated.

Practical significance

1. It has been established that the use of single-chamber VVI pacing in CHF patients with identified indications for pacemaker implantation leads to the progression of CHF; after one year the severity indicators of CHF are significantly worse than the baseline values, which indicates the inexpediency of using this pacing mode in CHF patients.

2. The method of stress echocardiography with reprogramming of the rate of the implanted PM has been introduced into clinical practice. The selection of individual pacing parameters using this method leads to positive dynamics of CHF, improved quality of life parameters, reduced frequency of hospitalizations, reduced medical care seeking, reduced need for PM reprogramming, and improved survival. A positive response to pacing using individual parameters determined by stress echocardiography does not depend on the pacing mode.

3. The character of the pain syndrome in patients with an implanted PM changes, and the use of echocardiography becomes the main method for detecting the progression of CHD. The proposed method of stress echocardiography with reprogramming of the pacing rate of the implanted pacemaker allows early detection of signs of coronary insufficiency. Patients with a moderate severity of PM syndrome are indicated for examination to detect the progression of CHD.

4. Intraventricular electromechanical asynchrony leads to the progression of CHF. The determination of electromechanical asynchrony has important prognostic significance and requires early active detection of its signs in order to timely refer them for treatment using cardiac resynchronization therapy. A diagnostic algorithm for detecting intraventricular asynchrony in CHF patients has been developed and tested.

5. Cardiac resynchronization therapy using biventricular pacing restores intraventricular synchrony, which is accompanied by long-term (within 3 years) positive dynamics of CHF, reduced frequency of hospitalizations and medical care seeking, improved quality of life, and improved survival compared with drug treatment.

6. When selecting patients for CRT, attention should be paid to such parameters of electromechanical asynchrony as the mechanical interventricular delay and the intraventricular asynchrony index (according to echocardiography using pulsed-wave Doppler and tissue Doppler imaging), and not only to QRS width. When selecting atrioventricular and interventricular delay parameters in patients with CRT using a biventricular pacemaker, it is necessary to use echocardiography with pulsed-wave Doppler and tissue Doppler myocardial imaging.

Implementation of the study results

The results of the study are used in the scientific and clinical activities of the Departments of Therapy and Cardiology of the State Institute for Advanced Medical Training of the Ministry of Defence of the Russian Federation, in the cardiology departments of the Main Military Clinical Hospital named after Academician N.N. Burdenko and the Central Military Hospital named after Academician A.A. Vishnevsky.

Approval of the dissertation

The main provisions of the work were presented as reports and discussed at the All-Army Conference on the Effectiveness of Treatment and Improvement of the Quality of Life of Patients with Cardiovascular Diseases (Moscow, 2005), the Moscow Society of Therapists (Moscow, 2007), the All-Russian Educational Internet Program for Physicians "Problems of the Internist" (2007), and the III International Symposium on Interventional Arrhythmology jointly with the educational seminar of the European Cardiac Arrhythmia Society (ECAS) "Modern Aspects of Pathogenesis, Diagnosis and Treatment of Supraventricular Tachyarrhythmias" (2007). Abstracts of materials: Moscow, 2007. — P. 93.

Based on the results of the work, the following have been published: "Methodological Recommendations for the Diagnosis and Treatment of Chronic Heart Failure", "Collection of Methodological Recommendations on Cardiology", "Guidelines for the Diagnosis and Treatment of Patients with Coronary Heart Disease", "Teaching Aid for the Diagnosis and Treatment of Left Ventricular Diastolic Function".

Publications

On the topic of the dissertation, 31 scientific works have been published, of which 11 are in central press.

Volume and structure of the dissertation

The dissertation is presented on 297 pages of typewritten text and consists of an introduction, 7 chapters (literature review, description of materials and research methods, own results and their discussion), conclusions, practical recommendations, appendices, and a list of references comprising 350 sources (118 domestic and 232 foreign authors). The text is illustrated with 89 tables and 38 figures.