BIO-2-HEART: Identification of Biomarkers in T2DM and Heart Failure
- Conditions
- Diabetes Mellitus, Type 2Heart Failure
- Interventions
- Diagnostic Test: 6-minute walk testDiagnostic Test: Study specific questionnaireProcedure: Blood collection
- Registration Number
- NCT03323216
- Lead Sponsor
- RWTH Aachen University
- Brief Summary
The primary aim of the current study is a better understanding of the role of Type 2 Diabetes Mellitus (T2DM) in heart failure and, in particular, changes in cardiac metabolism, which may contribute to heart failure. Various biomarkers in the coronary artery blood, as well as in the arterial and peripheral venous blood, are to be identified for this purpose. Included are patients with and without T2DM and with or without heart failure (HFpEF, HFmrEF, HFrEF), who have a clinically indicated and guidance-appropriate Cardiac Resynchronisation Therapy (CRT) implantation or pulmonary vein ablation/electrophysiological examination.
Not all patients currently benefit from the implantation of a CRT system (so-called non-responder). Despite narrow inclusion criteria, these "non-responders" cannot be unmasked in advance of the implantation. A further aim of this study is to identify biomarkers, which can be determined in advance of implantation to differentiate between responders and non-responders.
- Detailed Description
The primary aim of the current study is a better understanding of the role of Type 2 Diabetes Mellitus (T2DM) in heart failure and, in particular, changes in cardiac metabolism, which may contribute to heart failure. Various biomarkers in the coronary artery blood, as well as in the arterial and peripheral venous blood, are to be identified for this purpose. Included are patients with and without T2DM, who have a clinically indicated and guidance-appropriate Cardiac Resynchronisation Therapy (CRT) implantation due to their cardiac insufficiency and patients who have a clinically indicated electrophysiological examination (EPU) or pulmonary vein ablation (PVI).
Not all patients currently benefit from the implantation of a CRT system (so-called non-responder). Despite narrow inclusion criteria, these "non-responders" cannot be unmasked in advance of the implantation. Thus, a further aim of this study is to identify biomarkers, which can be determined in advance of implantation to differentiate between responders and non-responders.
Patient selection is based on the previously defined inclusion and exclusion criteria. The patient is informed by the physician and gives written consent to participate in the study. Prior to the implantation of the CRT system/the electrophysiological examination(EPU)/pulmonary vein ablation(PVI), the patient first responds to a study-related questionnaire and performs a 6-minute walk test.
Afterwards the clinically indicated, elective CRT implantation/EPU/PVI is performed by experienced physicians of the Medical Clinic I. Routinely, an arterial pressure catheter for invasive blood pressure monitoring (usually arteria radialis) is inserted. In addition, 2 peripheral venous accesses are established. The system of the CRT system is carried out via a small pectoral section. The cardiac probes are inserted into the heart via the subclavian vein. First, the probe is implanted in the right ventricle and, if necessary, a probe is placed in the right atrium. For EPU/PVI a femoral vein acsess is established.
To establish the coronary sinus (CS) probe, the intubation of the coronary sinus is performed by means of a guide catheter, which can be used to take blood samples. After intubation of the coronary sinus, the coronary artery blood is taken from the guide catheter for the study as well as arterially via the underlying pressure catheter as well as peripheral venous over a horizontal venous catheter. During EPU/PVI the coronary sinus has also to be intubated due to the ablation protocol. The blood sampling does not take more than 1-2 minutes.
The surgery is then terminated as planned and postoperative care is performed according to the standard operation procedure (SOP) of the Medical Clinic I. Within the framework of a control visit routinely performed in the Medical Clinic I , an echocardiographic follow-up of heart failure, a history assessment and a laboratory-based blood analysis are performed 6 months after CRT implantation. In the context of this visit peripheral venous blood is collected again for the study. In addition, the 6-minute walk test is performed once more and the patient receives the same questionnaire again.
Laboratory routine blood analysis is performed in the central laboratory of the University Hospital of Aachen and is independent of the study. The analysis measures standard parameters such as electrolytes, blood count, retention parameters, glucose, HbA1c, liver values, N-terminal Brain Natriuretic Peptide (NT-pro-BNP) etc. .
A blood gas analysis of the study blood is performed out first. The remaining blood is processed and stored at -80 ° C, so-called "biobank", for further biomarker analysis, e.g. metabolite analysis, peptides/proteins and RNA.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 400
- guideline-appropriate clinical indication for CRT implantation/electrophysiologial examination/pulmonary vein ablation
- age of majority
- written declaration of consent
- persons who are able to work and mentally able to follow the instructions of the study staff
- free access routes
- anemia Hb <8 mg / dl
- patients with acute infectious disease (e.g. pneumonia)
- non-intubatable coronary sinus
- patients who do not have access to the subclavian vein (e.g. thrombosis of the subclavian vein or superior vena cava)
- patients with idiopathic hypertrophic, restrictive or constrictive cardiomyopathy, or heart failure due to a known inflammatory or infiltrating disease (e.g. amyloidosis, sarcoidosis) or a constrictive disease
- patients with heart failure by sepsis
- persons with acute myocardial ischaemia, e.g. by angina pectoris or ECG changes under load
- patients with acute coronary syndrome are not implanted in the past 3 months
- patients who were hospitalized during the last month due to heart failure and who had to be treated intravenously with diuretics or inotropic substances
- patients with mechanical aortic valve or tricuspid valve
- patients with heart transplant.
- patients with acute liver or renal failure
- pregnant and lactating women
- patients placed under an official or judicial order in an institution
- patients who are in a dependency or employment relationship with the sponsor or auditor
- taking an investigational medicinal product 30 days before the start of the study
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description No diabetes 6-minute walk test Patients without diabetes Type 2 diabetes Blood collection Patients with diagnosis of type 2 diabetes (new/established) Prediabetes Study specific questionnaire Patients with an intermediate state of hyperglycemia with glycemic parameters above normal but below the diabetes threshold. No diabetes Study specific questionnaire Patients without diabetes Type 2 diabetes 6-minute walk test Patients with diagnosis of type 2 diabetes (new/established) Type 2 diabetes Study specific questionnaire Patients with diagnosis of type 2 diabetes (new/established) Prediabetes 6-minute walk test Patients with an intermediate state of hyperglycemia with glycemic parameters above normal but below the diabetes threshold. No diabetes Blood collection Patients without diabetes Prediabetes Blood collection Patients with an intermediate state of hyperglycemia with glycemic parameters above normal but below the diabetes threshold.
- Primary Outcome Measures
Name Time Method Glucose [mg/dl] 6 months after CRT-implantation Results of blood gas analysis:
Glucose \[mg/dl\]Aspartate aminotransferase [µg/L] 6 months after CRT-implantation Markers of myocardial ischemia and heart failure:
Aspartate aminotransferase \[µg/L\]Lactate dehydrogenase [µg/L] 6 months after CRT-implantation Markers of myocardial ischemia and heart failure:
Lactate dehydrogenase \[µg/L\]High-sensitive C-reactive protein (CRP) [µg/L] 6 months after CRT-implantation Cytokines and inflammation markers:
High-sensitive C-reactive protein (CRP) \[µg/L\]Procalcitonin (PCT) [µg/L] 6 months after CRT-implantation Cytokines and inflammation markers:
Procalcitonin (PCT) \[µg/L\]High-sensitive troponin T [µg/L] 6 months after CRT-implantation Markers of myocardial ischemia and heart failure:
High-sensitive troponin T \[µg/L\]N-terminal pro-B-type natriuretic peptide (NT-proBNP) [µg/L] 6 months after CRT-implantation Markers of myocardial ischemia and heart failure:
N-terminal pro-B-type natriuretic peptide (NT-proBNP) \[µg/L\]potential of hydrogen (pH) value [-] 6 months after CRT-implantation Results of blood gas analysis:
pH value \[-\]Interleukin 6 (IL-6) [µg/L] 6 months after CRT-implantation Cytokines and inflammation markers:
Interleukin 6 (IL-6) \[µg/L\]Carbon dioxide partial pressure (pCO2) [mmHg] 6 months after CRT-implantation Results of blood gas analysis:
Carbon dioxide partial pressure (pCO2) \[mmHg\]Base excess [mmol] 6 months after CRT-implantation Results of blood gas analysis:
Base excess \[mmol\]Electrolytes (K+, Na2+, Ca2+) [mmol/l] 6 months after CRT-implantation Results of blood gas analysis:
Electrolytes (K+, Na2+, Ca2+) \[mmol/l\]Oxygen partial pressure (pO2) [mmHg] 6 months after CRT-implantation Results of blood gas analysis:
Oxygen partial pressure (pO2) \[mmHg\]Lactate [mmol/l] 6 months after CRT-implantation Results of blood gas analysis:
Lactate \[mmol/l\]Total creatine kinase [µg/L] 6 months after CRT-implantation Markers of myocardial ischemia and heart failure:
Total creatine kinase \[µg/L\]Creatinine kinase-myocardial band (CK-MB) [µg/L] 6 months after CRT-implantation Markers of myocardial ischemia and heart failure:
Creatinine kinase-myocardial band (CK-MB) \[µg/L\]
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
University Hospital RWTH Aachen
🇩🇪Aachen, NRW, Germany