Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04489355 |
| Other study ID # |
Tomsk NRMC ICM |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 28, 2013 |
| Est. completion date |
May 1, 2024 |
Study information
| Verified date |
April 2024 |
| Source |
Tomsk National Research Medical Center of the Russian Academy of Sciences |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The study focuses on the development of a new personalized approach to diagnostics and
surgical treatment of patients with ischemic cardiomyopathy. The algorithm for selection of
patients for certain type of cardiac surgery will be developed. The models for prediction of
the risks and outcomes of cardiac surgery will be elaborated to reduce the rate of
complications in the early and long-term postoperative period in patients with ischemic
cardiomyopathy. Imaging modalities, methods for assessement of structural and functional
state of the myocardium, biochemistry testing, immunohistochemical examination, and
myocardial biopsy studies will be used to achieve these goals.
Description:
The aim of the study is to develop a new personalized approach to diagnostics and surgical
treatment of patients with ischemic cardiomyopathy.
Research Objectives:
1. To assess the prognostic values of scintigraphic indicators of myocardial perfusion,
contractility, and metabolism in patients with ischemic cardiomyopathy in regard to the
development of cardiac remodeling and adverse cardiovascular events in the mid term
after surgery.
2. To assess the prognostic values of parameters of cardiac magnetic resonance imaging
(cMRI) allowing to predict the risks of surgical intervention and chronic heart failure
progression in patients with ischemic cardiomyopathy.
3. To analyze the relationships between the structural and functional state of the
myocardium and the effectiveness of various types of surgery in patients with ischemic
cardiomyopathy. The structural and functional state of the myocardium is assessed by the
instrumental methods including myocardial scintigraphy, cMRI, stress echocardiography,
spiroergometry, and intraoperative fluometry.
4. To identify the myocardial biopsy-based predictors of adverse outcome in patients with
ischemic cardiomyopathy in the early and mid term postoperative period in patients with
ischemic cardiomyopathy.
5. To study the relationships between tissue and molecular biomarkers, severity of ischemic
cardiomyopathy, and the outcomes in patients with ischemic cardiomyopathy in the
postoperative period.
6. To introduce new and to optimize existing methods of surgical treatment in patients with
ischemic cardiomyopathy.
7. To develop an algorithmic model for assessing the risks and predicting outcomes of
surgical intervention in patients with ischemic cardiomyopathy in the postoperative
period.
Methods:
1. Clinical status of the patient: collection of complaints, medical history, physical
examination, assessment of anthropometric indicators (measurement of body weight,
height, BMI), and demographic indicators before and in the control period after surgical
treatment.
2. General clinical examination: standard 12-lead ECG, general urine analysis, general
blood analysis, blood chemistry, coagulation, chest x-ray, ultrasound of the carotid and
femoral arteries.
3. Echocardiography: determination of the type of aneurysm according to Di Donato;
measuring the distance between the papillary muscles of the left ventricle; assessing
the depth of co-optation of the mitral valve cusps; measuring Vena contracta; measuring
the radius of the proximal regurgitation zone, cm; Effective Regurgitant Orifice Area
(EROA, cm2); assessing systolic index and sphericity index. Stress echocardiography with
dobutamine. Before stress echocardiography on a Vivid E9 ultrasound system (GE,
Healthcare), continuous intravenous administration of dobutamine HEXAL, starting from 5
μg/kg/min and increasing its dose every 3 minutes to 10, 15, 20, 30, and 40 μg/kg.
4. Coronarography for assessing the anatomy and condition of the coronary pool using an
angiographic unit (Axiom Artis/Innova 2121-IQ (General Electric, USA)).
5. Contrast-enhanced cMRI to assess the following parameters:
- mass of viable left ventricular myocardium;
- volumes of cardiac cavities;
- diameter of the mitral and tricuspid valve rings with the determination of
regurgitation degree;
- the long axis of the ventricle;
- left ventricular ejection fraction;
- visualization of akinetic and hypokinetic myocardium;
- the presence of blood clots in the cavities of the heart;
6. Six-minute walk test.
7. Spiroergometry by SCHILLER complex with a GanshornPowerCube gas analyzer.
8. Determination of the plasma and serum levels of the NT-proBNP, endothelin-1, troponin I,
galectin-3, ST-2, matrix metalloproteinases (MMP) 2 and 9, and C-reactive protein.
9. Evaluation of myocardial perfusion by single-photon emission computed tomography using
radiopharmaceuticals 199 Tl chloride or 99m Tc. Myocardial perfusion scintigraphy with
Tc-methoxyisobutylisonitrile (99mTc-MIBI) and iodine-123-labeled
iodine-123-phenylmethylmethylene diode and metabolic scintigraphy with 123I-FMPDKc.
Stress ventriculography with 99-Tc-pyrophosphate by GKS-301T gamma camera (VNIIMP-VITA,
Russia).
10. Intraoperative fluometry of coronary grafts during coronary artery bypass grafting using
the Medistim VeriQ System.
11. Myocardial biopsy: it is planned to take myocardial biopsy samples in patients with
ischemic cardiomyopathy intraoperatively. In case of aneurysmectomy, myocardial biopsy
will be sampled in the middle left ventricular (LV) parts of the anterior, posterior,
lateral walls and the endocardium, the wall of the aneurysm and the portion of the right
atrial appendage, the right atrial appendage in the absence of aneurysmectomy. The
preparation of histological samples will be carried out in a standard way: fixation of
biopts in formalin with further filling in a paraffin medium and staining with
hematoxylin and eosin with determination of morphometric indicators. For histochemical
reactions, biopsy samples freshly frozen in liquid nitrogen will be used. The enzymatic
activity of succinant dehydrogenase (LDH), lactate dehydrogenase (LDH), and
3-hydroxybutyrate dehydrogenase (3-HBDH) will be studied using the Lojda tetrazolium
method according to the intensity of staining of the structure using the ImageJ program
(NIH, USA).
12. Statistical processing of data:
Structured collection of patient data will be performed in a database formed on the platform
of the Microsoft Excel 2010 software (Microsoft Corp., USA). Statistical processing of the
results will be carried out using the SPSS 23.0 for Windows software package (IBM Corp.,
Armonk, NY, USA). The normality of the law of distribution of quantitative indicators will be
checked using the Shapiro-Wilks criterion. Normally distributed parameters will be presented
as mean value (M) and standard deviation (StD) in the form M ± StD; not normally distributed
parameters will be presented as median (Me) and the 1st and 3rd interquantile intervals (Q25
- Q75) in the form of Me [Q25; Q75]. Qualitative data will be described by the frequency of
occurrence or its percentage. To find statistical dependences, to determine their strength
and direction, the Pearson correlation coefficient (r) (for normally distributed parameters)
and Spearman correlation coefficient (for for not normally distributed parameters and for
qualitative indicators in the ordinal scale) will be calculated. Using logistic regression,
significant predictors will be identified for the values of reverse remodeling in the long
term after surgical treatment. When conducting a multivariate analysis of interconnections,
first, by means of a univariate analysis, the main parameters that influence the studied
value will be identified, then, based on the search for intergroup correlations, the signs
that have a moderate or strong relationship will be eliminated, and multivariate modeling of
the relationships will be performed.
Survival analysis will be performed using the Kaplan-Meier method. All statistics will be
considered significant at p <0.05.
During the work, the methods of statistical analysis can be revised and (or) supplemented.
