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Observational studies of patients with coronary artery bypass grafting, associated with an unfavorable cardiopulmonary prognosis for at least one year after surgery.
This is Prospective, cohort, unblinded, observational comparable single center clinical trial. To compare the clinical, laboratory (including complete blood count, metabolic panel, and specific cardiac, inflammatory, infectious, and endothelial biomarkers), functional (ECG, echocardiography, ultrasound, spirometry, cardiopulmonary exercise testing), and radiological (chest X-ray/CT) phenotypes in patients with coronary artery bypass grafting with and without non-ventilator-associated postoperative, nosocomial pneumonia; to identify the factors of early and 1-years cardiopulmonary prognosis.
Increased risk of cardiovascular outcomes is related with the circulatory arrest, artificial circulation, perioperative trauma and respiratory complications of the postoperative period associating to the different severity and duration of the systemic inflammatory response, immune status disorders, hemostasis disorder, endothelial dysfunction, external respiration dysfunction, anatomic and functional disorders in the heart and lungs. Individual predictors of an unfavorable prognosis can be determined at the stage of before and just after surgery to conduct personalized prevention.
This study aimed to compare the clinical, laboratory (including complete blood count, metabolic panel, and specific cardiac, inflammatory, infectious, and endothelial biomarkers), functional (ECG, echocardiography, ultrasound, spirometry, cardiopulmonary exercise testing), and radiological (chest X-ray/CT) phenotypes in patients after coronary artery bypass grafting with and without non-ventilator-associated postoperative nosocomial pneumonia; to identify the factors of early and 1-years cardiopulmonary prognosis.
RESEARCH RELEVANCE Cardiovascular diseases (CVD), remain the leading cause of death worldwide. In 2017, mortality from cardiovascular diseases reached 862,895 people, or 587.6 per 100,000 of the population. Coronary artery disease (CAD) holds the leading position in the structure of causes of death from CVD. The annual mortality rate from CAD is 27%, with 42% of all deceased being of working age. Myocardial revascularization is one of the most common surgical procedures for the effective treatment of CAD. In the United States, over 200,000 coronary artery bypass grafting (CABG) surgeries are performed annually, with approximately 14% of patients being rehospitalized within 30 days after discharge and another 10% visiting emergency departments due to surgery-related complications and care issues. Pulmonary complications, primarily pneumonia (3%-42%), account for a significant proportion of the complications. Although pneumonia primarily affects the lungs, growing evidence suggests that it can have a negative impact on many systems and organs, particularly the cardiovascular system. The impact of pneumonia on the starting CVD consist the most evidences. The short-term and long-term impact of nosocomial pneumonia (NP) on the course of determined CVD, especially following myocardial revascularization performed using coronary bypass grafting (CABG) has not been previously assessed, and potential mechanisms have not been studied. It is known that the CABG leads to an enhanced systemic inflammatory response, is associated with nitric oxide deficiency, endothelial dysfunction, and procoagulant activity. Therefore, a postoperative complication in the form of NP in patients with multivessel CAD and not rare anatomic and functional myocardial disorders could potentially lead to a short-term additive enhancement of the inflammatory and endothelial response associated with the surgery, and to long-term activation of immune inflammation after CABG. The consequence of this may be an increased frequency of any complications within one year or more after surgery and a reduction in its effectiveness in reversing signs of coronary and heart failure. However, there is no confirmation of this assumption. The impact of pneumonia complications, such as respiratory failure, on the course of stable CAD is also insufficiently studied.
The study will be conducted at the Cardiology Research Institute - a branch of the Federal State Budgetary Scientific Institution "Tomsk National Research Medical Center of the Russian Academy of Sciences" (Cardiology Research Institute of the Tomsk NRMC) in Tomsk, Russia, from December 2024 to June 2027. The study was approved by the Biomedical Ethics Committee of the Cardiology Research Institute of the Tomsk NRMC on December 25, 2024. Informed consent will be obtained from all study participants after the nature, purpose, and potential risks of the study have been explained to them.
PRIMARY OBJECTIVE To test the hypothesis that in patients with stable coronary artery disease undergoing CABG, the occurrence of postoperative nosocomial pneumonia is associated with an adverse cardiopulmonary prognosis for at least one year after surgery.
SRCONDARY OBJECTIVES To compare the clinical, cellular, secretory, and instrumental profiles, as well as their in-hospital dynamics, between patients with an uncomplicated postoperative course and those complicated by nosocomial pneumonia.
To assess the sensitivity, specificity, and diagnostic accuracy of pulmonary and systemic criteria for diagnosing nosocomial pneumonia in patients with CAD following surgical myocardial revascularization; to identify the most specific systemic diagnostic criteria or propose new ones.
In a prospective one-year follow-up study of patients with CAD corrected by CABG, to evaluate the impact of nosocomial pneumonia on cardiopulmonary prognosis; to identify in-hospital predictors of an unfavorable prognosis for the purpose of personalized prevention.
The effectiveness of the study will be assessed by such a concept as "end point".
The primary endpoint was assessed at visits 5, 6, and 7 as the difference in parameters between the groups with pneumonia and without pneumonia and included the frequency of occurrence of one or more cardiovascular and/or respiratory endpoint events.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Main group with HAP after CABG | Patients with coronary artery disease (CAD) after Coronary Artery Bypass Grafting (CABG), complicated by postoperative nosocomial pneumonia. |
| |
| Control group without HAP after CABG | Patients with coronary artery disease (CAD) after Coronary Artery Bypass Grafting (CABG), without postoperative nosocomial pneumonia. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clinical, laboratory, and instrumental examination | Other | Clinical, laboratory, and instrumental examinations will be performed to achieve the specified primary and secondary endpoints. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of combined cardiovascular+respiratory endpoint (percentage); | The study will assess the incidence (percentage) of occurrence of combined cardiovascular+respiratory endpoint that includes the following events:
| 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Levels of procalcitonin (ng/ml); | Difference between groups in the levels of procalcitonin; | 12 months |
| Levels of interleukins 1 (pg/ml); | Difference between groups in the levels of interleukins 1. |
| Measure | Description | Time Frame |
|---|---|---|
| Systolic blood pressure (SBP) levels (mmHg); | Difference between groups in the levels of SBP | 12 months |
| Level of NT-proBNP (N-terminal pro-B-type natriuretic peptide) (pg/ml); | Difference between groups in the NT-proBNP level; |
Inclusion Criteria:
Pre-operative Exclusion Criteria:
Peri-operative Exclusion Criteria:
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Patient enrollment will take place at the Department of Atherosclerosis and Chronic Ischemic Heart Disease and the Department of Cardiovascular Surgery of the Cardiology Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences (Cardiology Research Institute, Tomsk NRMC).
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Roman S. Timoshenko, MD | Contact | +79539244630 | trs@cardio-tomsk.ru |
| Name | Affiliation | Role |
|---|---|---|
| Alla A. Boshchenko, MD, PhD | Cardiology Research Institute of Tomsk NRMC | Principal Investigator |
| Tatiana P Kalashnikova, MD, PhD | Cardiology Research Institute of Tomsk NRMC | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cardiology Research Institute of Tomsk NRMC | Recruiting | Tomsk | Tomsk Oblast | 634012 | Russia |
Deidentified individual participant data (text, tables, figures, and appendices), underlying the results of the trial, will be shared with researchers to achieve the aims in the approved proposal.
Proposals may be submitted up to 36 months following publication of the results of the trial. After 36 months, the data will be available in the Center's data ware house but without investigator support other than deposited metadata.
Information regarding submitting proposals and accessing data may be requested from the principal investigator by e-mail.
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| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| D000077299 | Healthcare-Associated Pneumonia |
| D011014 | Pneumonia |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D007753 | Laboratories |
| ID | Term |
|---|---|
| D000072182 | Non-Medical Public and Private Facilities |
| D006268 | Health Facilities |
| D005159 | Health Care Facilities Workforce and Services |
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Blood and urine speciments.
| 12 months |
| Changes in immune status (in percent); | Difference between groups in the changes in immune status; | 30 days |
| Level of endothelin-1 (ET-1) (pg/ml); | Difference between groups in the level of endothelin-1 (ET-1); | 6 months |
| Level of presepsin (pg/ml); | Difference between groups in the levels of presepsin | 6 months |
| Interleukins 6(pg/ml); | Difference between groups in the levels of interleukins 6; | 6 months |
| Tumor Necrosis Factor α (TNF-α)(pg/ml); | Difference between groups in the levels of TNF-α; | 6 months |
| Level of vascular endothelial growth factor (VEGF) (pg/ml); | Difference between groups in the level of vascular endothelial growth factor (VEGF); | 6 months |
| Difference between groups in the level of endocan (pg/ml); | Level of endocan . | 6 months |
| 6 months |
| Presence of life-threatening and symptomatic cardiac arrhythmias (in percent); | Difference between groups in the presence of life-threatening and symptomatic cardiac arrhythmias | 12 months |
| Severity of systemic inflammatory response syndrome manifestations (in percent); | Difference between groups in the severity of systemic inflammatory response syndrome manifestations (fever, leukocytosis, left shift in the leukocyte formula, categorized by phenotypes). | 12 months |
| Level of Troponin I (ng/ml); | Difference between groups in the Troponin I level; | 12 months |
| Heart failure class according to NYHA (New York Heart Association) (in percent); | Difference between groups in the Heart failure class according to NYHA | 12 months |
| Result of calculating inflammatory indices/scores (in percent); | Difference between groups in the result of calculating inflammatory indices/scores; | 12 months |
| Dynamics of ventilatory parameters during spiroergometry (in percent); | Difference between groups in the dynamics of ventilatory parameters during spiroergometry; | 12 months |
| Severity of ventilatory impairments during spirometry (in percent); | Difference between groups in the severity of ventilatory impairments during spirometry; | 12 months |
| Worsening of chronic heart failure by NYHA(New York Heart Association) Functional Class I or more during prospective follow-up (in percent); | Difference between groups in the worsening of CHF by NYHA Functional Class I or more during prospective follow-up; increase in dosage / initiation of diuretics; first-time prescription of antiarrhythmic drugs during prospective follow-up. | 12 months |
| Exercise tolerance during spiroergometry (in percent); | Difference between groups in the exercise tolerance during spiroergometry. | 6 months |
| Tiffeneau index (in percent); | Difference between groups in the Tiffeneau index, | 12 months |
| Frequency of glucocorticoid prescription (in percent); | Difference between groups in the frequency of glucocorticoid prescription; | 12 months |
| Frequency of transfer to the ICU (Intensive Care Unit) (in percent); | Difference between groups in the frequency of transfer to the ICU; | 30 days |
| Frequency of sepsis/septic shock development (in percent); | Difference between groups in the frequency of sepsis and septic shock development. | 12 months |
| Difference between groups in the onset of respiratory failure (RF) or its worsening by 1 grade or more (in percent); | Difference between groups in the onset of respiratory failure (RF) or its worsening by 1 grade or more during prospective follow-up; | 12 months |
| Exercise duration during spiroergometry, achieved heart rate (in percent); | Difference between groups in the exercise duration during spiroergometry, achieved heart rate; | 12 months |
| Level and dynamics of EQ-5D-5L quality of life questionnaire scores (in percent); | Difference between groups in the level and dynamics of EQ-5D-5L quality of life questionnaire scores; | 12 months |
| Need for and duration of respiratory support (in percent); | Difference between groups in the need for and duration of respiratory support; | 12 months |
| Level and dynamics of body temperature (°C); | Difference between groups in the level and dynamics of body temperature; | 30 days |
| Prescription of inhaled bronchodilators (in percent); | Difference between groups in the prescription of inhaled bronchodilators for continuous use during prospective follow-up. | 12 months |
| Forced expiratory volume (L/s); | Difference between groups in the forced expiratory volume is measured in liters per second (L/s). | 12 months |
| Forced vital capacity (L) | Difference between groups in the forced vital capacity is measured in liters (L). | 12 months |
| Vital capacity (L) | Difference between groups in the vital capacity is measured in liters (L). | 12 months |
| The Six-Minute Walk test (6MWT) (in meters); | Difference between groups in the Six-Minute Walk test (6MWT) | 12 months |
| Level of the Medical Research Council (from 0 to 4) dyspnea scale; | Difference between groups in the level of the Medical Research Council (from 0 to 4) dyspnea scale. 0 - Not troubled by breathlessness except on strenuous exercise
| 12 months |
| Respiratory rate (RR) (bpm); | Difference between groups in the respiratory rate is measured in breaths per minute. | 12 months |
| Length of hospital stay after surgery (days); | Difference between groups in the length of hospital stay after surgery; | 30 days |
| Level of peripheral capillary oxygen saturation (SpO2) (in percent); | Difference between groups in the SpO2 levels | 12 months |
| Medication adherence (in percent); | Difference between groups in the medication adherence; | 12 months |
| Degree of respiratory failure (in percent); | Difference between groups in the degree of respiratory failure; | 12 months |
| Any other postoperative complications (in percent); | Difference between groups in any other postoperative complications. | 12 months |
| Right ventricular fractional area change (RVFAC) (in percent); | Difference between groups in the Right ventricular fractional area change (RVFAC); | 12 months |
| Right ventricular systolic pressure (RVSP) (mmHg); | Difference between groups in the Right ventricular systolic pressure (RVSP); | 12 months |
| Left Ventricular Global Longitudinal Strain (LV GLS) (in percent); | Difference between groups in the Left Ventricular Global Longitudinal Strain | 12 months |
| Left ventricular end-diastolic volume index (EDVI); | Difference between groups in the left ventricular end-diastolic volume index (EDVI) | 12 months |
| Angina Functional Class (in percent); | Difference between groups in the Angina Functional Class | 12 months |
| Heart rate (HR) (bpm); | Difference between groups in heart rate is measured in beats per minute. | 12 months |
| Diastolic blood pressure (DBP) Levels (mm Hg); | Difference between groups in the levels of DBP; | 12 months |
| Left ventricular stroke index (SI) (in percent); | Difference between groups in the left ventricular stroke index (SI). | 12 months |
| Left ventricular ejection fraction (LVEF) (in percent); | Difference between groups in the left ventricular ejection fraction (LVEF). | 12 months |
| Wall motion score index (WMSI); | Difference between groups in the wall motion score index (WMSI); | 12 months |
| Frequency of significant ST-segment depression during spiroergometry (in percent); | Difference between groups in the frequency of significant ST-segment depression during spiroergometry. | 6 months |
| Depth and time of onset of ST-segment depression during spiroergometry (in percent); | Difference between groups in the depth of ST-segment depression during spiroergometry; | 6 months |
| Time of onset of ST-segment depression during spiroergometry (in percent); | Difference between groups in the time of onset of ST-segment depression during spiroergometry; | 6 months |
| Cardiac arrhythmias during spiroergometry (in percent); | Difference between groups in the cardiac arrhythmias during spiroergometry; | 6 months |
| Increase in dosage / initiation of diuretics; first-time prescription of antiarrhythmic drugs during prospective follow-up (in percent); | Difference between groups in the increase in dosage / initiation of diuretics during prospective follow-up. | 12 months |
| First-time prescription of antiarrhythmic drugs during prospective follow-up (in percent); | Difference between groups in the first-time prescription of antiarrhythmic drugs during prospective follow-up. | 12 months |
| Irina V. Kologrivova, MD, PhD |
| Cardiology Research Institute of Tomsk NRMC |
| Study Chair |
| Natalia V. Rebrova, MD, PhD | Cardiology Research Institute of Tomsk NRMC | Study Chair |
| Arina S Zinovieva, MD | Cardiology Research Institute of Tomsk NRMC | Study Chair |
| Ulia A Arseneva, MD | Cardiology Research Institute of Tomsk NRMC | Study Chair |
| D001161 |
| Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D003428 | Cross Infection |
| D007239 | Infections |
| D012141 | Respiratory Tract Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D007049 | Iatrogenic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |