Clinical trial NCT06393595: Prediction of Outcomes in Patients With Chronic Heart Failure Based on Tissue Raman Spectroscopy
Official title: Prediction of Outcomes in Patients With Chronic Heart Failure Based on Tissue Raman Spectroscopy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Heart Failure
Keywords: cumulative death
cardiovascular death (CVD)
CVD or hospitalization for heart failure exacerbation
surface enhanced Raman Spectroscopy
skin Raman Spectroscopy
Lead sponsor: Samara State Medical University
Sponsor class: OTHER
Collaborators: name: City Clinical Hospital No.1 named after N.I. Pirogov
First posted: 2024-05-01
Enrollment: 200
Sex: ALL
Minimum age (years): 35
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The researchers included participants from among those hospitalized in the cardiology department of an urban acute care hospital (groups 1,3,4)because of first-diagnosed chronic heart failure or its exacerbation.

Group 2 consisted of patients with clinically and instrumentally proven chronic ischemic heart disease without manifestations of CHF also hospitalized. Reasons for hospitalization in this group were related to BP elevation, paroxysms of atrial fibrillation/atrial flutter.

Selection into the study was made among consecutively admitted patients, provided that the inclusion criteria were met

Brief summary: Chronic heart failure (CHF) is a syndrome complicating heart disease, the prevalence of which has reached epidemic levels. According to global statistics the most common causes of CHF are coronary heart disease (CHD): 26.5%, arterial hypertension (AH):26.2% . The category of patients with CHD complicated by CHF prevails in clinical practice, requiring an optimized approach to determining prognosis in order to improve the effectiveness of therapy. In the literature, this issue has been studied with the use of general clinical, biochemical, instrumental criteria. Nevertheless, the problem of optimized prognosis in patients with CHF remains. Its solution may lie in the study of metabolic parameters of biological media - skin, blood serum by Raman spectroscopy.

Skin is an accessible tissue for studying the effects of a wide range of age-dependent noncommunicable diseases, including cardiovascular disease, type 2 diabetes mellitus, and chronic kidney disease. We were one of the first to use skin RS as a method of determining renal dysfunction, a necessary component of chronic kidney disease. However, the applicability of RS/SERS in the diagnosis and prognosis of specific diseases, as well as in the collection of statistical data for this analytical approach, remains an open question . Despite the fact that the method is classified as analytical, it can be used to identify not so much specific chemical molecules as their specific loci, which provide vibrations that change the wavelengths of the scattered spectrum. The resulting spectrum can be presented as a metabolic "portrait" of the disease, with the most informative loci, the combination of which is associated with a negative prognosis.

The innovative analytical methods of optical spectroscopy proposed in this project provide new level information about hundreds of molecules and their active centers that have prospects as biomarkers. This study aims to determine the clinical relevance of skin and serum RS in patients with CHF, realized on state-of-the-art instrumentation in a comprehensive patient study setting. The research proposed in this project will contribute to the development of high-tech production of new optical devices for rapid diagnosis and prognosis of a wide range of diseases.

Detailed description: This study included participants hospitalized in the cardiology unit of Samara city Clinical Hospital No.1 n.a. N.I.Pirogov of Emergency Medical Aid.The reason for hospitalization was newly diagnosed chronic heart failure or its exacerbation.

Objective: 1) to develop a personalized approach to prediction of total mortality, cardiovascular death in patients with CHD complicated by CHF on the basis of Raman spectra of skin, plasma, blood serum.

2)To develop a classification of Raman spectra characteristic for CHF, as well as its phenotypes and relevant comorbid conditions - Chronic kidney disease (CKD) and glycemic status.

Study Material:

1. Group with CHF based on CHD of both sexes aged 35 to 84 years (200 participants);
2. Group with CHD without CHF (70 participants);
3. Group with CHF with non-ischemic cardiomyopathies (50 participants);
4. group with CHF and valvular cardiomyopathies (40 participants)

The study design is divided into two consecutive parts:

A)cross-sectional cohort . B)prospective

Cross-sectional study (part 1). Material: groups 1-4.

Objectives:

1. To identify Raman spectral characteristics specific to the CHF syndrome, skin RS and serum SERS would be performed in groups of different CHF etiology: noncomplicated CHD ; CHD complicated by CHF; non-ischemic Cardiomyopathies (CMP) complicated by CHF(Dilated CMP, Inflammatory CMP,; valvular CMPs ).
2. To study the influence of CHF phenotypes (divided by Left Ventricular ejection fraction (LVEF)), as well as comorbidity - chronic kidney disease, type 2 diabetes mellitus(DM2) on skin and serum Raman spectra, biochemical parameters in the group with CHD.

   Prospective study (part 2) Study material: group 1.

   Objectives:
3. To establish the possibilities of serum SERS and skin RS parameters in predicting overall mortality in patients with CHD complicated by CHF in comparison with prediction models based on parameters of clinical, biochemical and instrumental routine techniques.
4. Develop prediction models for total mortality, CV mortality, and CV mortality in combination with hospitalizations for CHD participants with CHF .
5. To establish relationships with the most prognostically important spectral components of RS and known markers of atherosclerosis and cardiovascular diseases (CVD): CKD parameters; troponin T, glucose; cholesterol spectrum parameters.

Planned period of the cross-sectional phase of the study: November 2022 to May 2023.

Visit 1- Determination of inclusion/exclusion criteria for recruitment. Collection of clinical, biochemical, instrumental parameters. Determination of serum SERS and skin RS.

Planned period of the prospective study: November 2022-May 2024. Visit -1 is used to include only participants from group (1) in the prospective part of the study: CHD+CHF.

Visit-2 is planned at 4-6 months after the initial evaluation. The aim of visit-to assess patient's clinical status and compliance to prescribed medication.

Visit 3 (end of prospective follow-up ).The purpose of the visit - to collect information about hospitalizations and complications that occurred after visit 2. In case of death according to relatives' information, to confirm the fact of death in the electronic medical information analytical system (EMIAS).

Scientific novelty of the research: The technology of surface enhanced Raman spectroscopy (SERS) of blood serum on nanosilver substrate will be tested. Artificial intelligence technology is used for discriminative analysis based on SERS parameters.

Spectral features due to the influence of CVD, diabetes mellitus and renal dysfunction will be specified on RS of skin and serum SERS highlighted for the first time .

For the first time, the RS of skin, serum of non-ischemic CMPs and valvular CMPs is studied.

For the first time, a prognostic model using skin RS, SERS of patients with CHD complicated by CHF is proposed.

Based on the results of the study, models will be developed to predict mortality and cardiovascular complications in patients with CHD complicated by CHF.

Expected Results:

Mathematical models will be developed to predict cumulative mortality, CV mortality and cumulative target, including CV mortality and hospitalizations for exacerbations of CHF, based on independent predictors of biochemical, clinical, skin and serum Raman spectrometry parameters.

Spectral regions reflecting the influence of chronic heart failure syndrome as such will be identified (by comparing serum SERS of patients with different etiologies of CHF).

Spectral characteristics of three phenotypes of CHF will be identified: with preserved LVEF; moderately reduced LVEF; low LVEF.

Spectral characteristics specific for chronic kidney disease and DM2 will be identified.

Eligibility criteria: Inclusion Criteria:

Group 1(CHD+CHF): clinically evident CHF II-IV NYHA Classes,confirmed by NT-proBNP diagnostic levels. Any form of Coronary Heart Disease :angina pectoris up to and including 2 functional class, previous myocardial infarction, percutaneous coronary intervention or coronary arteries bypass grafts. possible functional insufficiency of A-V valves, arterial hypertension, possibly with chronic atrial fibrillation/atrial fibrillation of any form, ventricular extrasystoles of any class, Hiss bundle branch block not requiring implantation of devices, ability to self-care.

Group 2(CHD): Any form of Cronic Heart Disease :angina pectoris up to and including 2 functional class, previous myocardial infarction, percutaneous coronary intervention or coronary arteries bypass grafts, possible functional insufficiency of A-V valves of 1 stage, arterial hypertension, possibly with chronic atrial fibrillation/ flatter of any form, ventricular extrasystoles of any class, Hiss bundle branch block not requiring implantation of devices, ability to self-care.

Group 3 (NICMPs+CHF): clinically evident CHF II-IV NYHA Classes,confirmed by NT-proBNP diagnostic levels without signs of CHD in the history, without violation of coronary anatomy - stenoses (MSCT and coronary angiography). Possible functional insufficiency of A-B valves of the 1st degree, arterial hypertension, possible chronic forms of atrial fibrillation/ flatter, ventricular extrasystoles of any class, blockade of the Hiss legs not requiring implantation of devices, capable of self-care.

Group 4 (VCMPs+CHF):Valvular acquared cardiomyopathies with clinically evident CHF II-IV NYHA Classes,confirmed by NT-proBNP diagnostic levels without signs of CHD in the history, without violation of coronary anatomy - stenoses (MSCT and coronary angiography). Possible functional insufficiency of A-B valves of the 1st degree, arterial hypertension, possible chronic forms of atrial fibrillation/ flatter, ventricular extrasystoles of any class, blockade of the Hiss legs not requiring implantation of devices, capable of self-care.

Exclusion Criteria:Exclusion criteria (for groups 1-4): Acute myocardial infarction or unstable angina within the last 6 months, Dementia, lack of signed consent, CKD 4st or higher, tuberculosis, active cancer, liver cirrhosis of infectious etiology, chronic anemia : Hemoglobin less than 95 g/L, inability to self-care, type 1 diabetes mellitus,or insulin-dependent type 2 DM , anticipated heart valve surgery within one year, uncontrolled endocrine disease or malignancy likely to affect prognosis.

Primary outcomes:
measure: record in electronic medical information analitical system(EMIAS)
timeFrame: 01.11.2022-01.05.2024
measure: record in electronic medical information analitical system (EMIAS)
timeFrame: 01/11/2022-01/05/2024
Secondary outcomes:
measure: record in electronic medical information analitical system (EMIAS) and history of disease
timeFrame: 01/11/2022-01/05/2024
Other outcomes:
measure: Raman spectrum classification
timeFrame: 11/05/2023-20/06/2024
Locations:
city: Samara
country: Russian Federation
facility: city Samara hospital n.a. N.I.Pirogov
Study officials:
affiliation: chief of therapy chair of professional education department
name: Petr A Lebedev, professor
role: PRINCIPAL_INVESTIGATOR
References: