Diastolic heart failure in patients with type 2 diabetes mellitus combined with essential arterial hypertension

The dissertation is devoted to the study of diastolic chronic heart failure in patients with combined pathology — type 2 diabetes mellitus and essential arterial hypertension. The work aims to clarify the clinical features of diastolic CHF in this category of patients, to evaluate structural and functional changes of the heart with emphasis on the diastolic function of both the left and the right ventricles, and to analyse the 24-hour blood pressure profile. The possibilities of pharmacological correction of the revealed disorders using the angiotensin-converting enzyme inhibitor spirapril and the α-β-adrenoblocker carvedilol, including in comparison with monotherapy, are considered separately.

The scientific significance of the research is determined by a comprehensive approach to the assessment of diastolic dysfunction of both ventricles and interventricular interaction, which have been insufficiently covered in the literature for this comorbidity, as well as by the analysis of the dependence of structural and functional changes on the duration and degree of compensation of type 2 diabetes mellitus and arterial hypertension. The practical value of the work is associated with the substantiation of the need for early diagnosis of diastolic CHF in patients with the combination of type 2 DM and essential AH, and with the proposal of combined therapy with spirapril and carvedilol for this category of patients.

The problem of chronic heart failure (CHF) remains one of the most important issues for the healthcare systems of many countries around the world. Recently, interest in diastolic heart failure has increased, because the number of patients in whom symptoms of decompensation develop against the background of preserved left ventricular contractile function has grown [25, 89].

According to the Euro Heart Survey HF Study (2001), the proportion of patients with diastolic CHF is 30% [139]. The results of the Russian epidemiological study EPOKHA-CHF (2003) indicate that in 56.8% of examined patients with heart failure the ejection fraction was above 50%, and in 85.6% it was above 45% [95, 123].

The high prevalence of diastolic heart failure dictates the need for its early diagnosis and the timely initiation of effective therapy.

In Russia, the development of CHF is largely determined by essential arterial hypertension (AH) and type 2 diabetes mellitus (DM) [123, 139]. In this connection, the study of diastolic heart failure in patients with type 2 diabetes mellitus combined with essential arterial hypertension appears to be highly relevant.

The difficulties in detecting diastolic CHF in patients with combined pathology are considerable. This is due to the fact that the minimal manifestations of diastolic heart failure are often "masked" by the symptoms of the underlying disease (essential AH, type 2 DM) and its complications.

When analysing the available literature, only isolated works devoted to studying left ventricular diastolic function in patients with type 2 DM and AH can be found. The question of right ventricular diastolic function and interventricular interaction in patients with type 2 DM and AH remains unstudied.

At present, there are no clear recommendations for the treatment of diastolic heart failure. The main reason lies in the absence of a sufficient number of serious clinical observations on this problem. The results of studies that included patients with systolic heart failure are usually extrapolated to patients with impaired diastolic function, which makes treatment less effective.

In turn, the success and effectiveness of treatment of diastolic CHF is determined by the early and timely diagnosis of structural and functional changes in the heart.

Taking the above into account, the present work has been undertaken.

Aim of the study

To investigate the characteristics of diastolic heart failure and the possibilities of its pharmacological correction in patients with type 2 diabetes mellitus combined with essential arterial hypertension.

Objectives of the study

1. To clarify the clinical features of diastolic heart failure in patients with type 2 diabetes mellitus combined with essential arterial hypertension.

2. To evaluate the structural and functional parameters of the heart in diastolic heart failure caused by type 2 diabetes mellitus and essential arterial hypertension.

3. To study the diastolic function of both the left and the right ventricles of the heart, as well as interventricular interaction, in this category of patients.

4. To examine the 24-hour blood pressure profile in diastolic heart failure in patients with type 2 diabetes mellitus and arterial hypertension.

5. To analyse the dynamics of the above parameters under the influence of pharmacological therapy for diastolic heart failure.

Main propositions submitted for defence:

1. Analysis of the clinical course of diastolic heart failure and of the structural and functional parameters of the heart in patients with type 2 DM and essential AH has revealed a number of features concerning the development of pronounced structural changes in the myocardium and of diastolic dysfunction of both the left and the right ventricles of the heart in the presence of CHF of only FC I–II.

2. In diastolic heart failure in patients with type 2 DM combined with essential AH, without pathology of the respiratory system, RV diastolic function becomes impaired only after 10 years of uncontrolled AH and in the presence of marked decompensation of type 2 DM.

3. The 24-hour BP profile in patients with diastolic heart failure is characterised by systolic-diastolic AH, an increase in the time index and BP variability regardless of the time of day, and a predominance of "non-dippers" among the patients.

4. Therapy of diastolic heart failure with spirapril in combination with carvedilol is more effective compared with spirapril monotherapy in patients with type 2 diabetes mellitus combined with essential arterial hypertension.

Scientific novelty

For the first time, along with studying the features of the clinical course of diastolic heart failure in patients with type 2 diabetes mellitus and essential arterial hypertension, an analysis of the indices of the structural and functional state of the heart has been carried out.

For the first time, the diastolic function of not only the left but also the right ventricle, as well as interventricular interaction, have been investigated in patients with diastolic CHF caused by type 2 DM and essential AH.

For the first time in this category of patients, the dependence of structural and functional changes in the heart on the duration of essential arterial hypertension, type 2 diabetes mellitus and the degree of its compensation has been analysed.

The advantage of combined therapy of diastolic heart failure with the ACE inhibitor spirapril and the α-β-adrenoblocker with vasodilating properties carvedilol over spirapril monotherapy has been demonstrated in patients with type 2 diabetes mellitus combined with essential arterial hypertension.

Practical significance of the work

The necessity of assessing the diastolic function of both ventricles of the heart in patients with type 2 diabetes mellitus and essential arterial hypertension has been proved in order to ensure timely detection of diastolic heart failure. For its pharmacological treatment in this category of patients, it is recommended to use a combination of the ACE inhibitor spirapril and the α-β-adrenoblocker with vasodilating properties carvedilol.

Implementation of the study results

The results of the study have been implemented into the practice of the Neuroendocrinology Department of the N. A. Semashko Nizhny Novgorod Regional Clinical Hospital and into the teaching process of the V. G. Vogralik Department of Hospital Therapy of the Nizhny Novgorod State Medical Academy.

Approbation of the work

The materials and main propositions of the dissertation were presented at the I Congress of the Society of Heart Failure Specialists "Heart Failure 2006" (Moscow, 2006), at a meeting of the Nizhny Novgorod Regional Branch of the Russian Association of Endocrinologists (Nizhny Novgorod, 2008), at the 14th Nizhny Novgorod Session of Young Scientists (Nizhny Novgorod, 2009), and at a joint meeting of the staff of the V. G. Vogralik Department of Hospital Therapy and the Problem Commission "Internal Diseases, Cardiology, Toxicology, Allergology, Endocrinology, Pharmacology" (Nizhny Novgorod, 2009).

Publications

On the topic of the dissertation, 11 printed works have been published, including 2 articles in journals included by the Higher Attestation Commission of the Ministry of Education of the Russian Federation in the "List of periodic scientific publications recommended for the publication of scientific works reflecting the main scientific content of candidate dissertations."

Structure and scope of the work

The dissertation is presented on 163 pages of typewritten text. It consists of an introduction, a literature review, materials and methods, four chapters of original research, a conclusion, conclusions, practical recommendations, and a bibliography. The list of references contains 179 sources by domestic authors and 81 by foreign authors. The work is illustrated with 39 tables and 20 figures.